Publications by authors named "William H Gaze"

37 Publications

Human Health and Ocean Pollution.

Ann Glob Health 2020 12 3;86(1):151. Epub 2020 Dec 3.

Centre Scientifique de Monaco, MC.

Background: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood.

Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health.

Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention.

Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources - coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths.

Ecosystem Findings: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks.

Human Health Findings: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children's risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals - phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste - can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South - environmental injustice on a planetary scale.

Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth's resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted.Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored.Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries.

Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health.Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress.Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries.Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.
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http://dx.doi.org/10.5334/aogh.2831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731724PMC
December 2020

The 'SELection End points in Communities of bacTeria' (SELECT) Method: A Novel Experimental Assay to Facilitate Risk Assessment of Selection for Antimicrobial Resistance in the Environment.

Environ Health Perspect 2020 10 21;128(10):107007. Epub 2020 Oct 21.

European Centre for Environment and Human Health, University of Exeter Medical School, Cornwall, UK.

Background: Antimicrobial resistance (AMR) is one of the most significant health threats to society. A growing body of research demonstrates selection for AMR likely occurs at environmental concentrations of antibiotics. However, no standardized experimental approaches for determining selective concentrations of antimicrobials currently exist, preventing appropriate environmental and human health risk assessment of AMR.

Objectives: We aimed to design a rapid, simple, and cost-effective novel experimental assay to determine selective effect concentrations of antibiotics and to generate the largest experimental data set of selective effect concentrations of antibiotics to date.

Methods: Previously published methods and data were used to validate the assay, which determines the effect concentration based on reduction of bacterial community (wastewater) growth. Risk quotients for test antibiotics were generated to quantify risk.

Results: The assay (SELection End points in Communities of bacTeria, or the SELECT method) was used to rapidly determine selective effect concentrations of antibiotics. These were in good agreement with quantitative polymerase chain reaction effect concentrations determined within the same experimental system. The SELECT method predicted no effect concentrations were minimally affected by changes in the assay temperature, growth media, or microbial community used as the inoculum. The predicted no effect concentrations for antibiotics tested ranged from for ciprofloxacin to for erythromycin.

Discussion: The lack of evidence demonstrating environmental selection for AMR, and of associated human health risks, is a primary reason for the lack of action in the mitigation of release of antibiotics into the aquatic environment. We present a novel method that can reliably and rapidly fill this data gap to enable regulation and subsequent mitigation (where required) to lower the risk of selection for, and human exposure to, AMR in aquatic environments. In particular, ciprofloxacin and, to a lesser extent, azithromycin, cefotaxime, and trimethoprim all pose a significant risk for selection of AMR in the environment. https://doi.org/10.1289/EHP6635.
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http://dx.doi.org/10.1289/EHP6635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577113PMC
October 2020

Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration.

Commun Biol 2020 Sep 3;3(1):467. Epub 2020 Sep 3.

European Centre for Environment and Human Health, University of Exeter Medical School, ESI, University of Exeter, Penyrn Campus, Penryn, Cornwall, TR10 9EF, UK.

Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission's Water Framework Directive's priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1-2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.
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http://dx.doi.org/10.1038/s42003-020-01176-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471295PMC
September 2020

Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19.

Sci Total Environ 2020 Dec 31;749:141364. Epub 2020 Jul 31.

Centre for Environmental Biotechnology, School of Natural Sciences, Bangor University, Bangor, Gwynedd LL57 2UW, UK; School of Ocean Sciences, Bangor University, Menai Bridge, Anglesey LL59 5AB, UK.

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). A review of 48 independent studies revealed that severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 10-10 gc/ml) and feces (ca. 10-10 gc/ml) is much lower than in nasopharyngeal fluids (ca. 10-10 gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the gut and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears much lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that tens of million cases of COVID-19 have occurred globally, but exposure to feces or wastewater has never been implicated as a transmission vector.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836549PMC
December 2020

A global multinational survey of cefotaxime-resistant coliforms in urban wastewater treatment plants.

Environ Int 2020 11 21;144:106035. Epub 2020 Aug 21.

Department of Soil Chemistry, Plant Nutrition and Microbiology, Institute of Soil Water and Environmental Sciences, Volcani Center, Agricultural Research Organization, Rishon Lezion, Israel. Electronic address:

The World Health Organization Global Action Plan recommends integrated surveillance programs as crucial strategies for monitoring antibiotic resistance. Although several national surveillance programs are in place for clinical and veterinary settings, no such schemes exist for monitoring antibiotic-resistant bacteria in the environment. In this transnational study, we developed, validated, and tested a low-cost surveillance and easy to implement approach to evaluate antibiotic resistance in wastewater treatment plants (WWTPs) by targeting cefotaxime-resistant (CTX-R) coliforms as indicators. The rationale for this approach was: i) coliform quantification methods are internationally accepted as indicators of fecal contamination in recreational waters and are therefore routinely applied in analytical labs; ii) CTX-R coliforms are clinically relevant, associated with extended-spectrum β-lactamases (ESBLs), and are rare in pristine environments. We analyzed 57 WWTPs in 22 countries across Europe, Asia, Africa, Australia, and North America. CTX-R coliforms were ubiquitous in raw sewage and their relative abundance varied significantly (<0.1% to 38.3%), being positively correlated (p < 0.001) with regional atmospheric temperatures. Although most WWTPs removed large proportions of CTX-R coliforms, loads over 10 colony-forming units per mL were occasionally observed in final effluents. We demonstrate that CTX-R coliform monitoring is a feasible and affordable approach to assess wastewater antibiotic resistance status.
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http://dx.doi.org/10.1016/j.envint.2020.106035DOI Listing
November 2020

What is the research evidence for antibiotic resistance exposure and transmission to humans from the environment? A systematic map protocol.

Environ Evid 2020 3;9(1):12. Epub 2020 Jun 3.

European Centre for Environment and Human Health, College of Medicine and Health, Knowledge Spa, University of Exeter, Truro, TR1 3HD UK.

Background: Antimicrobial resistance (AMR) is a public health crisis that is predicted to cause 10 million deaths per year by 2050. The environment has been implicated as a reservoir of AMR and is suggested to play a role in the dissemination of antibiotic resistance genes (ARGs). Currently, most research has focused on measuring concentrations of antibiotics and characterising the abundance and diversity of ARGs and antibiotic resistant bacteria (ARB) in the environment. To date, there has been limited empirical research on whether humans are exposed to this, and whether exposure can lead to measureable impacts on human health. Therefore, the objective of this work is to produce two linked systematic maps to investigate previous research on exposure and transmission of AMR to humans from the environment. The first map will investigate the available research relating to exposure and transmission of ARB/ARGs from the environment to humans on a global scale and the second will investigate the prevalence of ARB/ARGs in various environments in the UK. These two maps will be useful for policy makers and research funders to identify where there are significant gluts and gaps in the current research, and where more primary and synthesis research needs to be undertaken.

Methods: Separate search strategies will be developed for the two maps. Searches will be run in 13 databases, and grey literature will be sought from key websites and engagement with experts. Hits will be managed in EndNote and screened in two stages (title/abstract then full text) against predefined inclusion criteria. A minimum of 10% will be double screened with ongoing consistency checking. All included studies will have data extracted into a bespoke form designed and piloted for each map. Data to be extracted will include bibliographic details, study design, location, exposure source, exposure route, health outcome (Map 1); and prevalence/percentage of ARB/ARG (Map 2). No validity appraisal will be undertaken. Results will be tabulated and presented narratively, together with graphics showing the types and areas of research that has been undertaken and heatmaps for key exposure-health outcomes (Map 1) and exposure-prevalence (Map 2).
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http://dx.doi.org/10.1186/s13750-020-00197-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268584PMC
June 2020

The role of stereochemistry of antibiotic agents in the development of antibiotic resistance in the environment.

Environ Int 2020 06 3;139:105681. Epub 2020 Apr 3.

Department of Chemistry, University of Bath, BA27AY Bath, United Kingdom. Electronic address:

Antibiotic resistance (ABR) is now recognised as a serious global health and economic threat that is most efficiently managed via a 'one health' approach incorporating environmental risk assessment. Although the environmental dimension of ABR has been largely overlooked, recent studies have underlined the importance of non-clinical settings in the emergence and spread of resistant strains. Despite this, several research gaps remain in regard to the development of a robust and fit-for-purpose environmental risk assessment for ABR drivers such as antibiotics (ABs). Here we explore the role the environment plays in the dissemination of ABR within the context of stereochemistry and its particular form, enantiomerism. Taking chloramphenicol as a proof of principle, we argue that stereoisomerism of ABs impacts on biological properties and the mechanisms of resistance and we discuss more broadly the importance of stereochemistry (enantiomerism in particular) with respect to antimicrobial potency and range of action.
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http://dx.doi.org/10.1016/j.envint.2020.105681DOI Listing
June 2020

A cross-sectional study on the prevalence of illness in coastal bathers compared to non-bathers in England and Wales: Findings from the Beach User Health Survey.

Water Res 2020 Jun 9;176:115700. Epub 2020 Mar 9.

European Centre for Environment and Human Health, University of Exeter Medical School, Truro, TR1 3HD, UK. Electronic address:

The risks of illness associated with bathing in UK coastal waters have not been quantified since the early 1990s. Efforts have been made since then to improve the quality of bathing waters. The aim of this study was to quantify the prevalence of symptoms of illness associated with sea bathing in bathers in England and Wales. A cross-sectional study was conducted between June 2014 and April 2015. An online survey collected information from sea bathers and non-bathers on their visits to beaches in England and Wales along with the occurrence of symptoms of illness. 2631 people (1693 bathers, 938 non-bathers) responded to the survey. Compared to non-bathers, bathers were more likely to report skin ailments (adjusted prevalence odds ratio (AOR) = 2.64, 95% confidence interval (CI) 1.23 to 5.65, p = 0.01), ear ailments (AOR = 3.77, 95% CI 1.84 to 7.73, p < 0.001), and any symptoms of illness (AOR = 3.73, 95% CI 2.63 to 5.29, p < 0.001). There was weak evidence of an increase in the odds of gastrointestinal illness (AOR = 1.59, 95% CI 0.96 to 2.65, p = 0.07), respiratory ailments (AOR = 2.44, 95% CI 0.92 to 6.48, p = 0.07) and eye ailments (AOR = 2.12, 95% CI 0.83 to 5.39, p = 0.11). While the study design does not allow inference of causality, we do observe an association between sea bathing in England and Wales and reported symptoms of ill health. This suggests that despite higher rates of compliance with water quality criteria among bathing waters nowadays, the odds of illness for bathers relative to non-bathers is similar in magnitude to estimates made in the 1990s.
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http://dx.doi.org/10.1016/j.watres.2020.115700DOI Listing
June 2020

Selection for antimicrobial resistance is reduced when embedded in a natural microbial community.

ISME J 2019 12 5;13(12):2927-2937. Epub 2019 Aug 5.

European Centre for Environment and Human Health, University of Exeter Medical School, ESI, Penryn, Cornwall, UK.

Antibiotic resistance has emerged as one of the most pressing, global threats to public health. In single-species experiments selection for antibiotic resistance occurs at very low antibiotic concentrations. However, it is unclear how far these findings can be extrapolated to natural environments, where species are embedded within complex communities. We competed isogenic strains of Escherichia coli, differing exclusively in a single chromosomal resistance determinant, in the presence and absence of a pig faecal microbial community across a gradient of antibiotic concentration for two relevant antibiotics: gentamicin and kanamycin. We show that the minimal selective concentration was increased by more than one order of magnitude for both antibiotics when embedded in the community. We identified two general mechanisms were responsible for the increase in minimal selective concentration: an increase in the cost of resistance and a protective effect of the community for the susceptible phenotype. These findings have implications for our understanding of the evolution and selection of antibiotic resistance, and can inform future risk assessment efforts on antibiotic concentrations.
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http://dx.doi.org/10.1038/s41396-019-0483-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864104PMC
December 2019

Why don't the British eat locally harvested shellfish? The role of misconceptions and knowledge gaps.

Appetite 2019 12 15;143:104352. Epub 2019 Jul 15.

European Centre for Environment and Human Health, University of Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall, TR1 3HD, UK.

Although the UK consumes a substantial amount of shellfish, most is imported (e.g. prawns), while locally harvested molluscs and crustaceans (e.g. mussels, crab) tend to be exported. This study aimed to investigate whether a low rate of local shellfish consumption in the UK is due to misunderstandings or knowledge gaps about the potential health and environmental risks and benefits of consumption. Following the Mental Models Approach, the present paper reveals: 1) qualitative results from 26 stakeholder/public interviews which identified 10 key misunderstandings and knowledge gaps, including incorrect beliefs about health risks and a lack of knowledge about the relative environmental benefits compared to other foods (key misunderstandings included some parts of a crab are poisonous if eaten, and the majority of UK shellfish is farmed), and 2) quantitative results from a survey (n = 1,433) that explored the degree to which these misunderstandings and knowledge gaps may influence consumption intentions in the wider UK population. Survey results suggested the number of misunderstandings and knowledge gaps significantly predicted shellfish consumption intentions even after controlling for demographics, food related values, and past consumption behaviour. Path analyses revealed their impact on intentions was partially mediated via Theory of Planned Behaviour variables. Results could inform information campaigns supporting consumers to make more informed decisions regarding a group of foods that are potentially both healthy and relatively environmentally friendly.
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http://dx.doi.org/10.1016/j.appet.2019.104352DOI Listing
December 2019

Comparing the selective and co-selective effects of different antimicrobials in bacterial communities.

Int J Antimicrob Agents 2019 Jun 16;53(6):767-773. Epub 2019 Mar 16.

European Centre for Environment and Human Health, University of Exeter Medical School, Environment & Sustainability Institute, Penryn Campus, Penryn, Cornwall, TR10 9FE.

Bacterial communities are exposed to a cocktail of antimicrobial agents, including antibiotics, heavy metals and biocidal antimicrobials such as quaternary ammonium compounds (QACs). The extent to which these compounds may select or co-select for antimicrobial resistance (AMR) is not fully understood. In this study, human-associated, wastewater-derived bacterial communities were exposed to either benzalkonium chloride (BAC), ciprofloxacin or trimethoprim at sub-point-of-use concentrations for one week to determine selective and co-selective potential. Metagenome analyses were performed to determine effects on bacterial community structure and prevalence of antibiotic resistance genes (ARGs) and metal or biocide resistance genes (MBRGS). Ciprofloxacin had the greatest co-selective potential, significantly enriching for resistance mechanisms to multiple antibiotic classes. Conversely, BAC exposure significantly reduced relative abundance of ARGs and MBRGS, including the well characterised qac efflux genes. However, BAC exposure significantly impacted bacterial community structure. Therefore BAC, and potentially other QACs, did not play as significant a role in co-selection for AMR as antibiotics such as ciprofloxacin at sub-point-of-use concentrations in this study. This approach can be used to identify priority compounds for further study, to better understand evolution of AMR in bacterial communities exposed to sub-point-of-use concentrations of antimicrobials.
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http://dx.doi.org/10.1016/j.ijantimicag.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546120PMC
June 2019

Carbapenem resistance in bacteria isolated from soil and water environments in Algeria.

J Glob Antimicrob Resist 2018 12 30;15:262-267. Epub 2018 Jul 30.

European Centre for Environment and Human Health, College of Medicine and Health, Knowledge Spa, Royal Cornwall Hospital, Truro TR1 3HD, UK. Electronic address:

Objectives: Recent research has demonstrated that natural populations of bacteria carry large numbers of mobile genetic elements that may harbour antibiotic resistance determinants. This study aimed to investigate carbapenem resistance in Gram-negative bacteria isolated from natural environments in Béjaïa (Algeria) and to determine the horizontal gene transfer potential of a subset of these antibiotic resistance genes (ARGs).

Methods: Antibiotic-resistant bacteria were isolated and the host was identified using MALDI-TOF/MS and 16S rRNA sequencing. ARG carriage was investigated by the double-disk synergy test, metallo-β-lactamase (MBL) production test and PCR screening for carbapenemase genes. Conjugation experiments were performed to determine potential ARG mobility. To identify ARGs, genomic libraries were constructed and functionally screened and inserts were sequenced.

Results: A total of 62 antibiotic-resistant strains isolated from soil and water samples were classified as belonging to the Enterobacteriaceae, Pseudomonadaceae, Xanthomonadaceae and Aeromonadaceae families. Four highly imipenem-resistant (MIC>64μg/mL) and cefotaxime-resistant (MIC>8μg/mL) clinically-relevant strains were selected for further characterisation. All four strains produced extended-spectrum β-lactamases, but MBL production was not confirmed. Imipenem and cefotaxime resistance was transferable to Escherichia coli but was not conferred by bla, bla, bla, bla, bla or bla genes. Novel putative resistance mechanisms were identified, including a novel DHA β-lactamase conferring clinical resistance to cefotaxime.

Conclusions: The environment is a reservoir of carbapenem-resistant bacteria. Further investigation of the evolution and dissemination of antibiotic resistance in environmental bacteria is required in order to understand and prevent the emergence of resistance in the clinical environment.
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http://dx.doi.org/10.1016/j.jgar.2018.07.013DOI Listing
December 2018

Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities.

mBio 2018 07 24;9(4). Epub 2018 Jul 24.

European Centre for Environment and Human Health, University of Exeter Medical School, Environment & Sustainability Institute, Penryn, Cornwall, United Kingdom

Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner. Antibiotic resistance is one of the greatest global issues facing society. Still, comparatively little is known about selection for resistance at very low antibiotic concentrations. We show that the strength of selection for clinically important resistance genes within a complex bacterial community can remain constant across a large antibiotic concentration range (wide selective space). Therefore, largely understudied ecological compartments could be just as important as clinical environments for selection of antibiotic resistance.
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http://dx.doi.org/10.1128/mBio.00969-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058293PMC
July 2018

CRISPR-Cas antimicrobials: Challenges and future prospects.

PLoS Pathog 2018 06 14;14(6):e1006990. Epub 2018 Jun 14.

Environment and Sustainability Institute, Centre for Ecology and Conservation, University of Exeter, Biosciences, Penryn, Cornwall, United Kingdom.

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http://dx.doi.org/10.1371/journal.ppat.1006990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001953PMC
June 2018

Water and sanitation: an essential battlefront in the war on antimicrobial resistance.

FEMS Microbiol Ecol 2018 09;94(9)

Department of Civil Engineering, The University of Hong Kong, Environmental Biotechnology Laboratory, The University of Hong Kong, Hong Kong.

Water and sanitation represent a key battlefront in combatting the spread of antimicrobial resistance (AMR). Basic water sanitation infrastructure is an essential first step towards protecting public health, thereby limiting the spread of pathogens and the need for antibiotics. AMR presents unique human health risks, meriting new risk assessment frameworks specifically adapted to water and sanitation-borne AMR. There are numerous exposure routes to AMR originating from human waste, each of which must be quantified for its relative risk to human health. Wastewater treatment plants play a vital role in centralized collection and treatment of human sewage, but there are numerous unresolved issues in terms of the microbial ecological processes occurring within them and the extent to which they attenuate or amplify AMR. Research is needed to advance understanding of the fate of resistant bacteria and antibiotic resistance genes in various waste management systems, depending on the local constraints and intended reuse applications. World Health Organization and national AMR action plans would benefit from a more holistic 'One Water' understanding. In this article we provide a framework for research, policy, practice and public engagement aimed at limiting the spread of AMR from water and sanitation in low-, medium- and high-income countries.
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http://dx.doi.org/10.1093/femsec/fiy101DOI Listing
September 2018

Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance.

Environ Int 2018 08 7;117:132-138. Epub 2018 May 7.

Swedish Agency for Marine and Water Management, Box 11 930, SE-404 39 Gothenburg, Sweden. Electronic address:

There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance..
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http://dx.doi.org/10.1016/j.envint.2018.04.041DOI Listing
August 2018

Is it safe to go back into the water? A systematic review and meta-analysis of the risk of acquiring infections from recreational exposure to seawater.

Int J Epidemiol 2018 04;47(2):572-586

European Centre for Environment and Human Health, University of Exeter Medical School, Truro, UK.

Background: Numerous illnesses are associated with bathing in natural waters, although it is assumed that the risk of illness among bathers exposed to relatively clean waters found in high-income countries is negligible. A systematic review was carried out to quantify the increased risk of experiencing a range of adverse health outcomes among bathers exposed to coastal water compared with non-bathers.

Methods: In all 6919 potentially relevant titles and abstracts were screened, and from these 40 studies were eligible for inclusion in the review. Odds ratios (OR) were extracted from 19 of these reports and combined in random-effect meta-analyses for the following adverse health outcomes: incident cases of any illness, ear infections, gastrointestinal illness and infections caused by specific microorganisms.

Results: There is an increased risk of experiencing symptoms of any illness [OR = 1.86, 95% confidence interval (CI): 1.31 to 2.64, P = 0.001] and ear ailments (OR = 2.05, 95% CI: 1.49 to 2.82, P < 0.001) in bathers compared with non-bathers. There is also an increased risk of experiencing gastrointestinal ailments (OR = 1.29, 95% CI: 1.12 to 1.49, P < 0.001).

Conclusions: This is the first systematic review to evaluate evidence on the increased risk of acquiring illnesses from bathing in seawater compared with non-bathers. Our results support the notion that infections are acquired from bathing in coastal waters, and that bathers have a greater risk of experiencing a variety of illnesses compared with non-bathers.
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http://dx.doi.org/10.1093/ije/dyx281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913622PMC
April 2018

The widespread dissemination of integrons throughout bacterial communities in a riverine system.

ISME J 2018 03 26;12(3):681-691. Epub 2018 Jan 26.

School of Life Sciences, University of Warwick, Coventry, UK.

Anthropogenic inputs increase levels of antimicrobial resistance (AMR) in the environment, however, it is unknown how these inputs create this observed increase, and if anthropogenic sources impact AMR in environmental bacteria. The aim of this study was to characterise the role of waste water treatment plants (WWTPs) in the dissemination of class 1 integrons (CL1s) in the riverine environment. Using sample sites from upstream and downstream of a WWTP, we demonstrate through isolation and culture-independent analysis that WWTP effluent significantly increases both CL1 abundance and antibiotic resistance in the riverine environment. Characterisation of CL1-bearing isolates revealed that CL1s were distributed across a diverse range of bacteria, with identical complex genetic resistance determinants isolated from both human-associated and common environmental bacteria across connected sites. Over half of sequenced CL1s lacked the 3'-conserved sequence ('atypical' CL1s); surprisingly, bacteria carrying atypical CL1s were on average resistant to more antibiotics than bacteria carrying 3'-CS CL1s. Quaternary ammonium compound (QAC) resistance genes were observed across 75% of sequenced CL1 gene cassette arrays. Chemical data analysis indicated high levels of boron (a detergent marker) downstream of the WWTP. Subsequent phenotypic screening of CL1-bearing isolates demonstrated that ~90% were resistant to QAC detergents, with in vitro experiments demonstrating that QACs could solely select for the transfer of clinical antibiotic resistance genes to a naive Escherichia coli recipient. In conclusion, this study highlights the significant impact of WWTPs on environmental AMR, and demonstrates the widespread carriage of clinically important resistance determinants by environmentally associated bacteria.
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http://dx.doi.org/10.1038/s41396-017-0030-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864220PMC
March 2018

Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water users: Environmental surveillance, exposure assessment, and epidemiological study (Beach Bum Survey).

Environ Int 2018 05 14;114:326-333. Epub 2018 Jan 14.

European Centre for Environment and Human Health, University of Exeter Medical School, Truro TR1 3HD, UK. Electronic address:

Background: Antibiotic-resistant bacteria (ARB) present a global public health problem. With numbers of community-acquired resistant infections increasing, understanding the mechanisms by which people are exposed to and colonised by ARB can help inform effective strategies to prevent their spread. The role natural environments play in this is poorly understood. This is the first study to combine surveillance of ARB in bathing waters, human exposure estimates and association between exposure and colonisation by ARB in water users.

Methods: 97 bathing water samples from England and Wales were analysed for the proportion of E. coli harbouring bla. These data were used to estimate the likelihood of water users ingesting bla-bearing E. coli. Having identified surfers as being at risk of exposure to ARB, a cross-sectional study was conducted. Regular surfers and non-surfers were recruited to assess whether there is an association between surfing and gut colonisation by blabearing E. coli.

Results: 11 of 97 bathing waters sampled were found to contain bla-bearing E. coli. While the percentage of bla-bearing E. coli in bathing waters was low (0.07%), water users are at risk of ingesting these ARB. It is estimated that over 2.5 million water sports sessions occurred in 2015 resulting in the ingestion of at least one bla-bearing E. coli. In the epidemiological survey, 9/143 (6.3%) surfers were colonised by bla-bearing E. coli, as compared to 2/130 (1.5%) of non-surfers (risk ratio=4.09, 95% CI 1.02 to 16.4, p=0.046).

Conclusions: Surfers are at risk of exposure to and colonisation by clinically important antibiotic-resistant E. coli in coastal waters. Further research must be done on the role natural environments play in the transmission of ARB.
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http://dx.doi.org/10.1016/j.envint.2017.11.003DOI Listing
May 2018

Wild small mammals as sentinels for the environmental transmission of antimicrobial resistance.

Environ Res 2017 04 22;154:28-34. Epub 2016 Dec 22.

Environment and Sustainability Institute, University of Exeter, Penryn Campus, Penryn, Cornwall TR10 9FE, UK.

Antimicrobial resistance (AMR) represents a serious threat to human health worldwide. We have tested the use of free-living small mammals (mice, voles and shrews) as sentinels of variation in the distribution of AMR in the environment and the potential for transmission from the natural environment to animal hosts. Escherichia coli isolated from the faeces of small mammals trapped at paired coastal and inland sites were tested for resistance to four antibiotics: trimethoprim, ampicillin, ciprofloxacin and cefotaxime. Coastal individuals were over twice as likely to carry AMR E. coli than inland individuals (79% and 35% respectively), and both between-site and between-species variation was observed. Animals from coastal populations also excreted increased numbers of AMR E. coli and a greater diversity of E. coli phylotypes, including human-associated pathogenic strains. Small mammals appear to be useful bioindicators of fine-scale spatial variation in the distribution of AMR and, potentially, of the risks of AMR transmission to mammalian hosts, including humans.
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http://dx.doi.org/10.1016/j.envres.2016.12.014DOI Listing
April 2017

Long-term antibiotic exposure in soil is associated with changes in microbial community structure and prevalence of class 1 integrons.

FEMS Microbiol Ecol 2016 10 5;92(10). Epub 2016 Aug 5.

European Centre for Environment and Human Health, University of Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro TR1 3HD, UK.

Antimicrobial resistance is one of the most significant challenges facing the global medical community and can be attributed to the use and misuse of antibiotics. This includes use as growth promoters or for prophylaxis and treatment of bacterial infection in intensively farmed livestock from where antibiotics can enter the environment as residues in manure. We characterised the impact of the long-term application of a mixture of veterinary antibiotics alone (tylosin, sulfamethazine and chlortetracycline) on class 1 integron prevalence and soil microbiota composition. Class 1 integron prevalence increased significantly (P < 0.005) from 0.006% in control samples to 0.064% in the treated plots. Soil microbiota was analysed using 16S rRNA gene sequencing and revealed significant alterations in composition. Of the 19 significantly different (P < 0.05) OTUs identified, 16 were of the Class Proteobacteria and these decreased in abundance relative to the control plots. Only one OTU, of the Class Cyanobacteria, was shown to increase in abundance significantly; a curiosity given the established sensitivity of this class to antibiotics. We hypothesise that the overrepresentation of Proteobacteria as OTUs that decreased significantly in relative abundance, coupled with the observations of an increase in integron prevalence, may represent a strong selective pressure on these taxa.
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http://dx.doi.org/10.1093/femsec/fiw159DOI Listing
October 2016

Structural and Biochemical Characterization of Rm3, a Subclass B3 Metallo-β-Lactamase Identified from a Functional Metagenomic Study.

Antimicrob Agents Chemother 2016 10 23;60(10):5828-40. Epub 2016 Sep 23.

School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom

β-Lactamase production increasingly threatens the effectiveness of β-lactams, which remain a mainstay of antimicrobial chemotherapy. New activities emerge through both mutation of previously known β-lactamases and mobilization from environmental reservoirs. The spread of metallo-β-lactamases (MBLs) represents a particular challenge because of their typically broad-spectrum activities encompassing carbapenems, in addition to other β-lactam classes. Increasingly, genomic and metagenomic studies have revealed the distribution of putative MBLs in the environment, but in most cases their activity against clinically relevant β-lactams and, hence, the extent to which they can be considered a resistance reservoir remain uncharacterized. Here we characterize the product of one such gene, blaRm3, identified through functional metagenomic sampling of an environment with high levels of biocide exposure. blaRm3 encodes a subclass B3 MBL that, when expressed in a recombinant Escherichia coli strain, is exported to the bacterial periplasm and hydrolyzes clinically used penicillins, cephalosporins, and carbapenems with an efficiency limited by high Km values. An Rm3 crystal structure reveals the MBL superfamily αβ/βα fold, which more closely resembles that in mobilized B3 MBLs (AIM-1 and SMB-1) than other chromosomal enzymes (L1 or FEZ-1). A binuclear zinc site sits in a deep channel that is in part defined by a relatively extended N terminus. Structural comparisons suggest that the steric constraints imposed by the N terminus may limit its affinity for β-lactams. Sequence comparisons identify Rm3-like MBLs in numerous other environmental samples and species. Our data suggest that Rm3-like enzymes represent a distinct group of B3 MBLs with a wide distribution and can be considered an environmental reservoir of determinants of β-lactam resistance.
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http://dx.doi.org/10.1128/AAC.00750-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038237PMC
October 2016

Coastal clustering of HEV; Cornwall, UK.

Eur J Gastroenterol Hepatol 2016 Mar;28(3):323-7

aEuropean Centre for Environment & Human Health, University of Exeter Medical SchoolbUniversity of Exeter Medical SchoolcCornwall Gastrointestinal UnitdDepartment of Clinical Microbiology, Royal Cornwall Hospital, TruroePublic Health England, St Austell, Cornwall, UK.

Background And Aims: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas.

Aim: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection.

Methods: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status.

Results: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation.

Conclusion: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.
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http://dx.doi.org/10.1097/MEG.0000000000000518DOI Listing
March 2016

Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters.

Environ Int 2015 Sep 30;82:92-100. Epub 2015 Mar 30.

European Centre for Environment and Human Health, University of Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK. Electronic address:

Infections caused by antibiotic resistant bacteria (ARB) are associated with poor health outcomes and are recognised globally as a serious health problem. Much research has been conducted on the transmission of ARB to humans. Yet the role the natural environment plays in the spread of ARB and antibiotic resistance genes is not well understood. Antibiotic resistant bacteria have been detected in natural aquatic environments, and ingestion of seawater during water sports is one route by which many people could be directly exposed. The aim was to estimate the prevalence of resistance to one clinically important class of antibiotics (third-generation cephalosporins (3GCs)) amongst Escherichia coli in coastal surface waters in England and Wales. Prevalence data was used to quantify ingestion of 3GC-resistant E. coli (3GCREC) by people participating in water sports in designated coastal bathing waters. A further aim was to use this value to derive a population-level estimate of exposure to these bacteria during recreational use of coastal waters in 2012. The prevalence of 3GC-resistance amongst E. coli isolated from coastal surface waters was estimated using culture-based methods. This was combined with the density of E. coli reported in designated coastal bathing waters along with estimations of the volumes of water ingested during various water sports reported in the literature to calculate the mean number of 3GCREC ingested during different water sports. 0.12% of E. coli isolated from surface waters were resistant to 3GCs. This value was used to estimate that in England and Wales over 6.3 million water sport sessions occurred in 2012 that resulted in the ingestion of at least one 3GCREC. Despite the low prevalence of resistance to 3GCs amongst E. coli in surface waters, there is an identifiable human exposure risk for water users, which varies with the type of water sport undertaken. The relative importance of this exposure is likely to be greater in areas where a large proportion of the population enjoys water sports. Millions of water sport sessions occurred in 2012 that were likely to have resulted in people ingesting E. coli resistant to a single class of antibiotics (3GCs). However, this is expected to be a significant underestimate of recreational exposure to all ARB in seawater. This is the first study to use volumes of water ingested during different water sports to estimate human exposure to ARB. Further work needs to be done to elucidate the health implications and clinical relevance of exposure to ARB in both marine and fresh waters in order to fully understand the risk to public health.
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http://dx.doi.org/10.1016/j.envint.2015.02.013DOI Listing
September 2015

The hidden resistome of retail chicken meat.

J Glob Antimicrob Resist 2015 Mar 14;3(1):44-46. Epub 2015 Jan 14.

School of Life Sciences, University of Warwick, Coventry, UK. Electronic address:

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http://dx.doi.org/10.1016/j.jgar.2014.11.003DOI Listing
March 2015

Validated predictive modelling of the environmental resistome.

ISME J 2015 Jun 13;9(6):1467-76. Epub 2015 Feb 13.

School of Life Sciences, University of Warwick, Coventry, UK.

Multi-drug-resistant bacteria pose a significant threat to public health. The role of the environment in the overall rise in antibiotic-resistant infections and risk to humans is largely unknown. This study aimed to evaluate drivers of antibiotic-resistance levels across the River Thames catchment, model key biotic, spatial and chemical variables and produce predictive models for future risk assessment. Sediment samples from 13 sites across the River Thames basin were taken at four time points across 2011 and 2012. Samples were analysed for class 1 integron prevalence and enumeration of third-generation cephalosporin-resistant bacteria. Class 1 integron prevalence was validated as a molecular marker of antibiotic resistance; levels of resistance showed significant geospatial and temporal variation. The main explanatory variables of resistance levels at each sample site were the number, proximity, size and type of surrounding wastewater-treatment plants. Model 1 revealed treatment plants accounted for 49.5% of the variance in resistance levels. Other contributing factors were extent of different surrounding land cover types (for example, Neutral Grassland), temporal patterns and prior rainfall; when modelling all variables the resulting model (Model 2) could explain 82.9% of variations in resistance levels in the whole catchment. Chemical analyses correlated with key indicators of treatment plant effluent and a model (Model 3) was generated based on water quality parameters (contaminant and macro- and micro-nutrient levels). Model 2 was beta tested on independent sites and explained over 78% of the variation in integron prevalence showing a significant predictive ability. We believe all models in this study are highly useful tools for informing and prioritising mitigation strategies to reduce the environmental resistome.
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http://dx.doi.org/10.1038/ismej.2014.237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438333PMC
June 2015

Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution.

ISME J 2015 Jun 12;9(6):1269-79. Epub 2014 Dec 12.

Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.

Around all human activity, there are zones of pollution with pesticides, heavy metals, pharmaceuticals, personal care products and the microorganisms associated with human waste streams and agriculture. This diversity of pollutants, whose concentration varies spatially and temporally, is a major challenge for monitoring. Here, we suggest that the relative abundance of the clinical class 1 integron-integrase gene, intI1, is a good proxy for pollution because: (1) intI1 is linked to genes conferring resistance to antibiotics, disinfectants and heavy metals; (2) it is found in a wide variety of pathogenic and nonpathogenic bacteria; (3) its abundance can change rapidly because its host cells can have rapid generation times and it can move between bacteria by horizontal gene transfer; and (4) a single DNA sequence variant of intI1 is now found on a wide diversity of xenogenetic elements, these being complex mosaic DNA elements fixed through the agency of human selection. Here we review the literature examining the relationship between anthropogenic impacts and the abundance of intI1, and outline an approach by which intI1 could serve as a proxy for anthropogenic pollution.
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http://dx.doi.org/10.1038/ismej.2014.226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438328PMC
June 2015

Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistance.

Environ Health Perspect 2013 Sep 9;121(9):993-1001. Epub 2013 Jul 9.

US Environmental Protection Agency, Office of Research and Development, Cincinnati, Ohio 45268, USA.

Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks.

Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens.

Methods: The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options.

Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways.

Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.
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http://dx.doi.org/10.1289/ehp.1206316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764079PMC
September 2013

Influence of humans on evolution and mobilization of environmental antibiotic resistome.

Emerg Infect Dis 2013 Jul;19(7)

Exeter University, Truro, UK.

The clinical failure of antimicrobial drugs that were previously effective in controlling infectious disease is a tragedy of increasing magnitude that gravely affects human health. This resistance by pathogens is often the endpoint of an evolutionary process that began billions of years ago in non-disease-causing microorganisms. This environmental resistome, its mobilization, and the conditions that facilitate its entry into human pathogens are at the heart of the current public health crisis in antibiotic resistance. Understanding the origins, evolution, and mechanisms of transfer of resistance elements is vital to our ability to adequately address this public health issue.
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http://dx.doi.org/10.3201/eid1907.120871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713965PMC
July 2013

The scourge of antibiotic resistance: the important role of the environment.

Clin Infect Dis 2013 Sep 30;57(5):704-10. Epub 2013 May 30.

Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada.

Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.
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http://dx.doi.org/10.1093/cid/cit355DOI Listing
September 2013