Publications by authors named "Andrew Spiers"

51 Publications

External cephalic version: Predictors for success.

J Gynecol Obstet Hum Reprod 2021 May 15;50(9):102165. Epub 2021 May 15.

Department of Obstetrics & Gynecology, University Hospital of Angers, Angers, France. Electronic address:

Objectives: The objective of this study was to identify the factors predictive of the success of external cephalic version (ECV).

Methods: A single-centre retrospective observational study was performed in the maternity ward of the Angers University Hospital, France, between January 2010 and May 2020. The study included all patients (n = 613) for whom an ECV was performed for a breech or transverse foetus. The primary endpoint was measured by the success of the ECV, defined by the visualisation, using pelvic ultrasound, of the foetus in cephalic presentation immediately after the manoeuvre. Following to the ECV, the cohort was separated into two groups; ECV Success and ECV Failure. In order to determine the predictive factors of success, a logistic regression model was performed, including the parameters of: parity, foetal presentation during ECV, the side of the foetal back, placental location, type of operator and maternal age. The results are presented as (odds ratio [confidence intervals]; p-value). The significance threshold was defined by a p-value < 0.05.

Results: The ECV success rate was 21.4% (131/613). The factors predictive of the success of ECV were: transverse foetal presentation (2.7 [1.3-5.6]; p<0.01); a senior physician operator (1.6 [1.2-2]; p<0.01); multiparity (1.6 [1.2-2]; p<0.01); non anterior placental localization (1.4 [1.1-2]; p<0.01). A number of attempts greater than 3 were significantly associated with reduced chances of success (0.3 [0.2-0.4]; p<0.01).

Conclusion: The study shows that transverse foetal presentation, a senior physician operator, multiparity, as well as a non-anterior placental location are factors predictive of the success of ECV. Knowledge of these factors can improve the information given to patients.
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http://dx.doi.org/10.1016/j.jogoh.2021.102165DOI Listing
May 2021

Delivery Mode After Manual Rotation of Occiput Posterior Fetal Positions: A Randomized Controlled Trial.

Obstet Gynecol 2021 06;137(6):999-1006

Department of Obstetrics, the Department of Biostatistics and Methodology, the Department of Neonatal Medicine, the Department of Reproductive Medicine, Angers University Hospital, and the MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers, and CESP-INSERM, U1018, Team 7, Reproductive and Sexual Health, Paris-Sud University, Kremlin-Bicêtre, France.

Objective: To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery.

Methods: In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05.

Results: Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference -1.6; 95% CI -14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference -3.7; 95% CI -16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI -2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups.

Conclusion: Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance.

Clinical Trial Registration: ClinicalTrials.gov, NCT03009435.
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http://dx.doi.org/10.1097/AOG.0000000000004386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132900PMC
June 2021

The impact of the COVID-19 coronavirus pandemic on the surgical management of gynecological cancers: Analysis of the multicenter database of the French SCGP and the FRANCOGYN group.

J Gynecol Obstet Hum Reprod 2021 Mar 28;50(8):102133. Epub 2021 Mar 28.

Departement of Obstetrics and Gynecology, Angers University Hospital, Angers, France; CESP-INSERM, U1018, Team 7, Reproductive and sexual health, Paris-Sud University, 94276 Villejuif, France. Electronic address:

Introduction: The coronavirus SARS-CoV-2 (COVID-19) pandemic has put tremendous pressure on the French healthcare system. Almost all hospital departments have had to profoundly modify their activity to cope with the crisis. In this context, the surgical management of cancers has been a topic of debate as care strategies were tailored to avoid any delay in treatment that could be detrimental to patient wellbeing while being careful not to overload intensive care units. The primary objective of this study was to observe changes in the surgical management of pelvic cancers during the COVID-19 pandemic in France.

Material And Methods: This study analyzed data from the prospective multi-center cohort study conducted by the French Society for Pelvic and Gynecological Surgery (SCGP) with methodological support from the French (FRANCOGYN) Group. All members of the SCGP received by e-mail a link allowing them to include patients who were scheduled to undergo gynecological carcinologic surgery between March 16th 2020 and May 11th 2020. Demographic data, the characteristics of cancers and the impact of the crisis in terms of changes to the usual recommended coarse of care were collected.

Results: A total of 181 patients with a median age 63 years were included in the cohort. In total, 31 patients had cervical cancer, 76 patients had endometrial cancer, 52 patients had ovarian or tubal cancer, 5 patients had a borderline tumor of the ovary, and 17 patients had vulvar cancer. During the study period, the care strategy was changed for 49 (27%) patients with postponed for 35 (19.3%) patients, and canceled for 7 (3.9%) patients. Surgical treatment was maintained for 139 (76.8%) patients. Management with neoadjuvant chemotherapy was offered to 19 (10,5%) patients and a change in surgical choice was made for 5 (2,8%) patients. In total, 8 (4,4%) patients tested positive for COVID-19. Data also shows a greater number of therapeutic changes in cases of ovarian cancer as well as a cancelation of a lumbo-aortic lymphadenectomy in one patient with cervical cancer. Hospital consultants estimated a direct detrimental impact of the COVID-19 pandemic for 39 patients, representing 22% of gynecological cancers.

Conclusion: This study provided observational data of the impact of the COVID-19 health crisis on the surgical management of gynecological cancers.
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http://dx.doi.org/10.1016/j.jogoh.2021.102133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004475PMC
March 2021

Mitochondria: their role in spermatozoa and in male infertility.

Hum Reprod Update 2021 Feb 8. Epub 2021 Feb 8.

MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers 49000, France.

Background: The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants.

Objective And Rational: This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility.

Search Methods: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA', 'spermatozoa' or 'sperm' and 'reactive oxygen species' or 'calcium' or 'apoptosis' or signaling pathways'. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles.

Outcomes: Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity.

Wider Implications: The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.
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http://dx.doi.org/10.1093/humupd/dmab001DOI Listing
February 2021

Community biofilm-formation, stratification and productivity in serially-transferred microcosms.

FEMS Microbiol Lett 2020 01;367(24)

School of Applied Sciences, Abertay University, Bell Street, Dundee, DD1 1HG, UK.

The establishment of O2 gradients in liquid columns by bacterial metabolic activity produces a spatially-structured environment. This produces a high-O2 region at the top that represents an un-occupied niche which could be colonised by biofilm-competent strains. We have used this to develop an experimental model system using soil-wash inocula and a serial-transfer approach to investigate changes in community-based biofilm-formation and productivity. This involved 10 transfers of mixed-community or biofilm-only samples over a total of 10-60 days incubation. In all final-transfer communities the ability to form biofilms was retained, though in longer incubations the build-up of toxic metabolites limited productivity. Measurements of microcosm productivity, biofilm-strength and attachment levels were used to assess community-aggregated traits which showed changes at both the community and individual-strain levels. Final-transfer communities were stratified with strains demonstrating a plastic phenotype when migrating between the high and low-O2 regions. The majority of community productivity came from the O2-depleted region rather than the top of the liquid column. This model system illustrates the complexity we expect to see in natural biofilm-forming communities. The connection between biofilms and the liquid column seen here has important implications for how these structures form and respond to selective pressure.
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http://dx.doi.org/10.1093/femsle/fnaa187DOI Listing
January 2020

Three biofilm types produced by a model pseudomonad are differentiated by structural characteristics and fitness advantage.

Microbiology (Reading) 2020 08;166(8):707-716

School of Applied Sciences, Abertay University, Bell Street, Dundee DD1 1HG, UK.

Model bacterial biofilm systems suggest that bacteria produce one type of biofilm, which is then modified by environmental and physiological factors, although the diversification of developing populations might result in the appearance of adaptive mutants producing altered structures with improved fitness advantage. Here we compare the air-liquid (A-L) interface viscous mass (VM) biofilm produced by SBW25 and the wrinkly spreader (WS) and complementary biofilm-forming strain (CBFS) biofilm types produced by adaptive SBW25 mutants in order to better understand the link between these physical structures and the fitness advantage they provide in experimental microcosms. WS, CBFS and VM biofilms can be differentiated by strength, attachment levels and rheology, as well as by strain characteristics associated with biofilm formation. Competitive fitness assays demonstrate that they provide similar advantages under static growth conditions but respond differently to increasing levels of physical disturbance. Pairwise competitions between biofilms suggest that these strains must be competing for at least two growth-limiting resources at the A-L interface, most probably O and nutrients, although VM and CBFS cells located lower down in the liquid column might provide an additional fitness advantage through the colonization of a less competitive zone below the biofilm. Our comparison of different SBW25 biofilm types illustrates more generally how varied biofilm characteristics and fitness advantage could become among adaptive mutants arising from an ancestral biofilm-forming strain and raises the question of how significant these changes might be in a range of medical, biotechnological and industrial contexts where diversification and change may be problematic.
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http://dx.doi.org/10.1099/mic.0.000938DOI Listing
August 2020

Penetrating the air-liquid interface is the key to colonization and wrinkly spreader fitness.

Microbiology (Reading) 2019 10;165(10):1061-1074

School of Applied Sciences, Abertay University, Dundee DD1 1HG, UK.

In radiating populations of SBW25, adaptive wrinkly spreader (WS) mutants are able to gain access to the air-liquid (A-L) interface of static liquid microcosms and achieve a significant competitive fitness advantage over other non-biofilm-forming competitors. Aerotaxis and flagella-based swimming allows SBW25 cells to move into the high-O region located at the top of the liquid column and maintain their position by countering the effects of random cell diffusion, convection and disturbance (i.e. physical displacement). However, wild-type cells showed significantly lower levels of enrichment in this region compared to the archetypal WS, indicating that WS cells employ an additional mechanism to transfer to the A-L interface where displacement is no longer an issue and a biofilm can develop at the top of the liquid column. Preliminary experiments suggest that this might be achieved through the expression of an as yet unidentified surface active agent that is weakly associated with WS cells and alters liquid surface tension, as determined by quantitative tensiometry. The effect of physical displacement on the colonization of the high-O region and A-L interface was reduced through the addition of agar or polyethylene glycol to increase liquid viscosity, and under these conditions the competitive fitness of the WS was significantly reduced. These observations suggest that the ability to transfer to the A-L interface from the high-O region and remain there without further expenditure of energy (through, for example, the deployment of flagella) is a key evolutionary innovation of the WS, as it allows subsequent biofilm development and significant population increase, thereby affording these adaptive mutants a competitive fitness advantage over non-biofilm-forming competitors located within the liquid column.
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http://dx.doi.org/10.1099/mic.0.000844DOI Listing
October 2019

Priming winter wheat seeds with the bacterial quorum sensing signal N-hexanoyl-L-homoserine lactone (C6-HSL) shows potential to improve plant growth and seed yield.

PLoS One 2019 25;14(2):e0209460. Epub 2019 Feb 25.

School of Science, Engineering and Technology, Abertay University, Dundee, United Kingdom.

Several model plants are known to respond to bacterial quorum sensing molecules with altered root growth and gene expression patterns and induced resistance to plant pathogens. These compounds may represent novel elicitors that could be applied as seed primers to enhance cereal crop resistance to pathogens and abiotic stress and to improve yields. We investigated whether the acyl-homoserine lactone N-hexanoyl-L-homoserine lactone (C6-HSL) impacted winter wheat (Triticum aestivum L.) seed germination, plant development and productivity, using two Ukrainian varieties, Volodarka and Yatran 60, in both in vitro experiments and field trials. In vitro germination experiments indicated that C6-HSL seed priming had a small but significant positive impact on germination levels (1.2x increase, p < 0.0001), coleoptile and radicle development (1.4x increase, p < 0.0001). Field trials over two growing seasons (2015-16 and 2016-17) also demonstrated significant improvements in biomass at the tillering stage (1.4x increase, p < 0.0001), and crop structure and productivity at maturity including grain yield (1.4-1.5x increase, p < 0.0007) and quality (1.3x increase in good grain, p < 0.0001). In some cases variety effects were observed (p ≤ 0.05) suggesting that the effect of C6-HSL seed priming might depend on plant genetics, and some benefits of priming were also evident in F1 plants grown from seeds collected the previous season (p ≤ 0.05). These field-scale findings suggest that bacterial acyl-homoserine lactones such as C6-HSL could be used to improve cereal crop growth and yield and reduce reliance on fungicides and fertilisers to combat pathogens and stress.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209460PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388923PMC
October 2019

Interaction between CYP2D6 inhibitor antidepressants and codeine: is this relevant?

Expert Opin Drug Metab Toxicol 2018 Aug 12;14(8):879-886. Epub 2018 Jul 12.

c INSERM , UMR 1246 - SPHERE, MethodS in Patients-centered outcomes and HEalth ResEarch , Nantes and Tours , France.

Introduction: Co-occurring pain impairs depression's prognosis. Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) are first-line pharmacotherapies for depression and inhibit many cytochrome 2D6 enzymes. Codeine is a first-line treatment for pain and needs to be metabolized into morphine by cytochrome 2D6 to exert its analgesic effect. Concomitant prescription of both pharmacotherapies leads to inadequate analgesia. Areas covered: We performed a systematic review of the literature to amalgamate the current knowledge regarding the clinical effect of this association and quantified its prevalence in clinical practice in the French Pays de la Loire area using a retrospective observational cohort study design. Expert opinion: The literature review highlighted that antidepressants with moderate-to-strong inhibition of CYP2D6 should be avoided in patients receiving codeine. However, 0.44% of the 12,296 sampled patients received concomitant codeine and CYP2D6 inhibitor between January 2015 and June 2015. Switching drugs in both painful and depressive patients depends on the pain and depression subtypes. Promising drugs that both show an effect on pain and depression are currently being studied but are not usable in clinical practice. Until then, tailored communication reinforcement toward health-care professionals is needed to prevent these problematic occurrences of concomitant prescription administration.
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http://dx.doi.org/10.1080/17425255.2018.1496236DOI Listing
August 2018

The mental health of our sovereigns: The case of King Charles VI of France.

Bipolar Disord 2018 05 2;20(3):293-294. Epub 2018 Mar 2.

CHU de Nantes, Addictology and Liaison Psychiatry Department, Nantes University Hospital, Nantes, France.

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http://dx.doi.org/10.1111/bdi.12634DOI Listing
May 2018

Uncovering behavioural diversity amongst high-strength Pseudomonas spp. surfactants at the limit of liquid surface tension reduction.

FEMS Microbiol Lett 2018 02;365(4)

School of Science, Engineering and Technology, Abertay University, Bell Street, Dundee, DD1 1HG, UK.

Bacterial biosurfactants have a wide range of biological functions and biotechnological applications. Previous analyses had suggested a limit to their reduction of aqueous liquid surface tensions (γMin), and here we confirm this in an analysis of 25 Pseudomonas spp. strains isolated from soil which produce high-strength surfactants that reduce surface tensions to 25.2 ± 0.1-26.5 ± 0.2 mN m-1 (the surface tension of sterile growth medium and pure water was 52.9 ± 0.4 mN m-1 and 72.1 ± 1.2 mN m-1, respectively). Comparisons of culture supernatants produced using different growth media and semi-purified samples indicate that the limit of 24.2-24.7 mN m-1 is not greatly influenced by culture conditions, pH or NaCl concentrations. We have used foam, emulsion and oil-displacement behavioural assays as a simple and cost-effective proxy for in-depth biochemical characterisation, and these suggest that there is significant structural diversity amongst these surfactants that may reflect different biological functions and offer new biotechnological opportunities. Finally, we obtained a draft genome for the strain producing the highest strength surfactant, and identified a cluster of non-ribosomal protein synthase genes that may produce a cyclic lipopeptide (CLP)-like surfactant. Further investigation of this group of related bacteria recovered from the same site will allow a better understanding of the significance of the great variety of surfactants produced by bacterial communities found in soil and elsewhere.
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http://dx.doi.org/10.1093/femsle/fny008DOI Listing
February 2018

Opioid Antagonists for Pharmacological Treatment of Gambling Disorder: Are they Relevant?

Curr Neuropharmacol 2018 ;16(10):1418-1432

INSERM UMR1246 SPHERE Methods in Patients-centered outcomes and Health Research, University of Nantes and Tours, Nantes, France.

Background: To date, no drugs have been approved for gambling disorder. Numerous publications have described the value of opioid antagonists. Indeed, the mesocorticolimbic dopaminergic pathway has been suggested as the underlying cause of reward-seeking behaviour, and it is modulated by the opioid system.

Objective: This study aims to evaluate the relevance of opioid antagonists for treating GD.

Method: A systematic literature review was conducted. A search of the PubMed electronic database, PsycINFO and the Cochrane Systematic Review Database without any limits was performed.

Results: There is little information concerning the effects of opioid antagonists on GD. The total search with "nalmefene and gambling" without any limits revealed only 11 articles. The search with "naltrexone and gambling" without any limits generated 47 articles. Nevertheless, the best available data support the use of opioid antagonists, particularly in individuals with a history of alcohol use disorder or strong gambling urges.

Conclusion: Future trials are still needed. Indeed, opioid antagonists effectiveness has been investigated in only a limited number of patients, clinical trials do not reflect the heterogeneity of GD and there is little knowledge of the predictive factors of response to treatments. Moreover, differential affinity to nalmefene for kappa receptors may be associated with a particular effect in a yet to be defined addiction phenotype. Head to head comparisons between naltrexone and nalmefene would be helpful in combining other medication or psychotherapy. The identification of subgroups of patients that are more likely to benefit from opioid antagonists should be a goal.
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http://dx.doi.org/10.2174/1570159X15666170718144058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295935PMC
November 2018

Adaptive radiation of Pseudomonas fluorescens SBW25 in experimental microcosms provides an understanding of the evolutionary ecology and molecular biology of A-L interface biofilm formation.

FEMS Microbiol Lett 2017 07;364(12)

School of Science, Engineering and Technology, Abertay University, Dundee DD1 1HG, UK.

Combined experimental evolutionary and molecular biology approaches have been used to investigate the adaptive radiation of Pseudomonas fluorescens SBW25 in static microcosms leading to the colonisation of the air-liquid interface by biofilm-forming mutants such as the Wrinkly Spreader (WS). In these microcosms, the ecosystem engineering of the early wild-type colonists establishes the niche space for subsequent WS evolution and colonisation. Random WS mutations occurring in the developing population that deregulate diguanylate cyclases and c-di-GMP homeostasis result in cellulose-based biofilms at the air-liquid interface. These structures allow Wrinkly Spreaders to intercept O2 diffusing into the liquid column and limit the growth of competitors lower down. As the biofilm matures, competition increasingly occurs between WS lineages, and niche divergence within the biofilm may support further diversification before system failure when the structure finally sinks. A combination of pleiotropic and epistasis effects, as well as secondary mutations, may explain variations in WS phenotype and fitness. Understanding how mutations subvert regulatory networks to express intrinsic genome potential and key innovations providing a selective advantage in novel environments is key to understanding the versatility of bacteria, and how selection and ecological opportunity can rapidly lead to substantive changes in phenotype and in community structure and function.
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http://dx.doi.org/10.1093/femsle/fnx109DOI Listing
July 2017

Conflicting selection alters the trajectory of molecular evolution in a tripartite bacteria-plasmid-phage interaction.

Mol Ecol 2017 May 3;26(10):2757-2764. Epub 2017 Apr 3.

Department of Animal and Plant Sciences, University of Sheffield, Sheffield, S10 2TN, UK.

Bacteria engage in a complex network of ecological interactions, which includes mobile genetic elements (MGEs) such as phages and plasmids. These elements play a key role in microbial communities as vectors of horizontal gene transfer but can also be important sources of selection for their bacterial hosts. In natural communities, bacteria are likely to encounter multiple MGEs simultaneously and conflicting selection among MGEs could alter the bacterial evolutionary response to each MGE. Here, we test the effect of interactions with multiple MGEs on bacterial molecular evolution in the tripartite interaction between the bacterium, Pseudomonas fluorescens, the lytic bacteriophage, SBW25φ2, and conjugative plasmid, pQBR103, using genome sequencing of experimentally evolved bacteria. We show that individually, both plasmids and phages impose selection leading to bacterial evolutionary responses that are distinct from bacterial populations evolving without MGEs, but that together, plasmids and phages impose conflicting selection on bacteria, constraining the evolutionary responses observed in pairwise interactions. Our findings highlight the likely difficulties of predicting evolutionary responses to multiple selective pressures from the observed evolutionary responses to each selective pressure alone. Understanding evolution in complex microbial communities comprising many species and MGEs will require that we go beyond studies of pairwise interactions.
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http://dx.doi.org/10.1111/mec.14080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655702PMC
May 2017

Biofilm formation and cellulose expression by Bordetella avium 197N, the causative agent of bordetellosis in birds and an opportunistic respiratory pathogen in humans.

Res Microbiol 2017 Jun 26;168(5):419-430. Epub 2017 Jan 26.

School of Science, Engineering and Technology, Abertay University, Bell Street, Dundee DD1 1HG, UK. Electronic address:

Although bacterial cellulose synthase (bcs) operons are widespread within the Proteobacteria phylum, subunits required for the partial-acetylation of the polymer appear to be restricted to a few γ-group soil, plant-associated and phytopathogenic pseudomonads, including Pseudomonas fluorescens SBW25 and several Pseudomonas syringae pathovars. However, a bcs operon with acetylation subunits has also been annotated in the unrelated β-group respiratory pathogen, Bordetella avium 197N. Our comparison of subunit protein sequences and GC content analyses confirms the close similarity between the B. avium 197N and pseudomonad operons and suggests that, in both cases, the cellulose synthase and acetylation subunits were acquired as a single unit. Using static liquid microcosms, we can confirm that B. avium 197N expresses low levels of cellulose in air-liquid interface biofilms and that biofilm strength and attachment levels could be increased by elevating c-di-GMP levels like the pseudomonads, but cellulose was not required for biofilm formation itself. The finding that B. avium 197N is capable of producing cellulose from a highly-conserved, but relatively uncommon bcs operon raises the question of what functional role this modified polymer plays during the infection of the upper respiratory tract or survival between hosts, and what environmental signals control its production.
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http://dx.doi.org/10.1016/j.resmic.2017.01.002DOI Listing
June 2017

New Insights into the Effects of Several Environmental Parameters on the Relative Fitness of a Numerically Dominant Class of Evolved Niche Specialist.

Int J Evol Biol 2016 22;2016:4846565. Epub 2016 Dec 22.

School of Science, Engineering and Technology, Abertay University, Bell Street, Dundee DD1 1HG, UK.

Adaptive radiation in bacteria has been investigated using Wrinkly Spreaders (WS), a morphotype which colonises the air-liquid (A-L) interface of static microcosms by biofilm formation with a significant fitness advantage over competitors growing lower down in the O-limited liquid column. Here, we investigate several environmental parameters which impact the ecological opportunity that the Wrinkly Spreaders exploit in this model system. Manipulation of surface area/volume ratios suggests that the size of the WS niche was not as important as the ability to dominate the A-L interface and restrict competitor growth. The value of this niche to the Wrinkly Spreaders, as determined by competitive fitness assays, was found to increase as O flux to the A-L interface was reduced, confirming that competition for O was the main driver of WS fitness. The effect of O on fitness was also found to be dependent on the availability of nutrients, reflecting the need to take up both for optimal growth. Finally, the meniscus trap, a high-O region formed by the interaction of the A-L interface with the vial walls, was also important for fitness during the early stages of biofilm formation. These findings reveal the complexity of this seemingly simple model system and illustrate how changes in environmental physicality alter ecological opportunity and the fitness of the adaptive morphotype.
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http://dx.doi.org/10.1155/2016/4846565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214101PMC
December 2016

Parachuting: a dangerous trend in recreational psychoactive substance delivery.

Expert Opin Drug Deliv 2017 Apr 22;14(4):491-498. Epub 2016 Aug 22.

b EA 4275, SPHERE, Methods for Patients-centered outcomes and Health Research , Nantes University Hospital , Nantes , France.

Introduction: Medicine diversion for recreational use is a constant concern for health authorities. Parachuting, also refered to as bombing, is used in order to increase the expected effect, to accelerate time-to-onset and to create mixtures of medicines and substances. Aeras covered: Firstly, we analyzed all available scientific literature (PRISMA) and internet forums without any limiting timeframe. Secondly, we collected cases of parachuting reported in the west of France by the addictovigilance and poison control centres. Our study confirms the reality of this emerging issue associated with a higher medical risk (60% of intoxication cases were moderate-to-severe in our study). The substances involved in parachuting were primarily stimulants, with a majority of MDMA, although the use of diverted medication and psychotropes is also of concern. Expert opinion: Parachuting is a dangerous way of using substances and of diverting medicines. This type of administration gives users a certain pharmacokinetic latitude to 'play' with respect to substances and medicines. Medicine abuse deterrent formulations do not seem to be sufficient in preventing diversions. This dangerous method of using substances and of diverting medicines should drive pharmaceutical companies to innovate in the interest of public health and safety.
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http://dx.doi.org/10.1080/17425247.2016.1222371DOI Listing
April 2017

Rapid compensatory evolution promotes the survival of conjugative plasmids.

Mob Genet Elements 2016 May-Jun;6(3):e1179074. Epub 2016 May 4.

Department of Biology, University of York , York, UK.

Conjugative plasmids play a vital role in bacterial adaptation through horizontal gene transfer. Explaining how plasmids persist in host populations however is difficult, given the high costs often associated with plasmid carriage. Compensatory evolution to ameliorate this cost can rescue plasmids from extinction. In a recently published study we showed that compensatory evolution repeatedly targeted the same bacterial regulatory system, GacA/GacS, in populations of plasmid-carrying bacteria evolving across a range of selective environments. Mutations in these genes arose rapidly and completely eliminated the cost of plasmid carriage. Here we extend our analysis using an individual based model to explore the dynamics of compensatory evolution in this system. We show that mutations which ameliorate the cost of plasmid carriage can prevent both the loss of plasmids from the population and the fixation of accessory traits on the bacterial chromosome. We discuss how dependent the outcome of compensatory evolution is on the strength and availability of such mutations and the rate at which beneficial accessory traits integrate on the host chromosome.
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http://dx.doi.org/10.1080/2159256X.2016.1179074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964889PMC
August 2016

Transcutaneous Ultrasonography in Early Postoperative Diagnosis of Vocal Cord Palsy After Total Thyroidectomy.

World J Surg 2016 Mar;40(3):665-71

Service de Clinique Chirurgicale Digestive et Endocrinienne, CHU Nantes, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.

Purpose: This study evaluated the efficiency of transcutaneous laryngeal ultrasonography (TLUS) as an alternative to direct flexible laryngoscopy (DFL) in the early postoperative screening of vocal cord palsy (VCP) after total thyroidectomy, performed for benign and non-extensive malignant disease.

Methods: A prospective study was performed on patients who underwent total thyroidectomy between October 2013 and January 2015 at the Nantes University Hospital (France). Patients underwent DFL on postoperative day 1 performed by an otolaryngologist, followed by TLUS performed by a radiologist on postoperative day 1 or 2.

Results: One hundred and three (103) patients were included in this study, 17.5% were male and 82.5% were female, with a mean age of 51 ± 12 years. Nine patients (9.5%) were diagnosed with postoperative VCP using DFL of these cases 2 were not completely resolved at 3 months postoperatively. Three cases of VCP (33%) were diagnosed using TLUS. TLUS had a sensitivity of 33% and a negative predictive value (NPV) of 95% for the diagnosis of postoperative VCP. Vocal cords (VC) were unassessable in 27.2% of patients. Unassessable VC were significantly associated with male gender (p = 0.0001), age (p = 0.0001), weight (p = 0.002), operating time (p = 0.032), postoperative drainage (p = 0.001), and thyroid weight (p = 0.001). Independent risk factors in the multivariate analysis were male gender (p = 0.0001) and age (p = 0.0001). In the group of women under 50-year old, TLUS had a sensitivity of 50% and a NPV of 97.4%.

Conclusion: TLUS sensitivity is insufficient in early postoperative screening of VCP after thyroid surgery. Ultrasonographic VCP diagnosis should be confirmed with DFL.
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http://dx.doi.org/10.1007/s00268-015-3393-xDOI Listing
March 2016

Plasmid carriage can limit bacteria-phage coevolution.

Biol Lett 2015 Aug;11(8)

Department of Biology, University of York, York YO10 5DD, UK.

Coevolution with bacteriophages is a major selective force shaping bacterial populations and communities. A variety of both environmental and genetic factors has been shown to influence the mode and tempo of bacteria-phage coevolution. Here, we test the effects that carriage of a large conjugative plasmid, pQBR103, had on antagonistic coevolution between the bacterium Pseudomonas fluorescens and its phage, SBW25ϕ2. Plasmid carriage limited bacteria-phage coevolution; bacteria evolved lower phage-resistance and phages evolved lower infectivity in plasmid-carrying compared with plasmid-free populations. These differences were not explained by effects of plasmid carriage on the costs of phage resistance mutations. Surprisingly, in the presence of phages, plasmid carriage resulted in the evolution of high frequencies of mucoid bacterial colonies. Mucoidy can provide weak partial resistance against SBW25ϕ2, which may have limited selection for qualitative resistance mutations in our experiments. Taken together, our results suggest that plasmids can have evolutionary consequences for bacteria that go beyond the direct phenotypic effects of their accessory gene cargo.
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http://dx.doi.org/10.1098/rsbl.2015.0361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571675PMC
August 2015

Parallel compensatory evolution stabilizes plasmids across the parasitism-mutualism continuum.

Curr Biol 2015 Aug 16;25(15):2034-9. Epub 2015 Jul 16.

Department of Biology, University of York, York YO10 5DD, UK. Electronic address:

Plasmids drive genomic diversity in bacteria via horizontal gene transfer [1, 2]; nevertheless, explaining their survival in bacterial populations is challenging [3]. Theory predicts that irrespective of their net fitness effects, plasmids should be lost: when parasitic (costs outweigh benefits), plasmids should decline due to purifying selection [4-6], yet under mutualism (benefits outweigh costs), selection favors the capture of beneficial accessory genes by the chromosome and loss of the costly plasmid backbone [4]. While compensatory evolution can enhance plasmid stability within populations [7-15], the propensity for this to occur across the parasitism-mutualism continuum is unknown. We experimentally evolved Pseudomonas fluorescens and its mercury resistance mega-plasmid, pQBR103 [16], across an environment-mediated parasitism-mutualism continuum. Compensatory evolution stabilized plasmids by rapidly ameliorating the cost of plasmid carriage in all environments. Genomic analysis revealed that, in both parasitic and mutualistic treatments, evolution repeatedly targeted the gacA/gacS bacterial two-component global regulatory system while leaving the plasmid sequence intact. Deletion of either gacA or gacS was sufficient to completely ameliorate the cost of plasmid carriage. Mutation of gacA/gacS downregulated the expression of ∼17% of chromosomal and plasmid genes and appears to have relieved the translational demand imposed by the plasmid. Chromosomal capture of mercury resistance accompanied by plasmid loss occurred throughout the experiment but very rarely invaded to high frequency, suggesting that rapid compensatory evolution can limit this process. Compensatory evolution can explain the widespread occurrence of plasmids and allows bacteria to retain horizontally acquired plasmids even in environments where their accessory genes are not immediately useful.
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http://dx.doi.org/10.1016/j.cub.2015.06.024DOI Listing
August 2015

Bacteriophages limit the existence conditions for conjugative plasmids.

mBio 2015 Jun 2;6(3):e00586. Epub 2015 Jun 2.

Department of Biology, University of York, York, United Kingdom.

Unlabelled: Bacteriophages are a major cause of bacterial mortality and impose strong selection on natural bacterial populations, yet their effects on the dynamics of conjugative plasmids have rarely been tested. We combined experimental evolution, mathematical modeling, and individual-based simulations to explain how the ecological and population genetics effects of bacteriophages upon bacteria interact to determine the dynamics of conjugative plasmids and their persistence. The ecological effects of bacteriophages on bacteria are predicted to limit the existence conditions for conjugative plasmids, preventing persistence under weak selection for plasmid accessory traits. Experiments showed that phages drove faster extinction of plasmids in environments where the plasmid conferred no benefit, but they also revealed more complex effects of phages on plasmid dynamics under these conditions, specifically, the temporary maintenance of plasmids at fixation followed by rapid loss. We hypothesized that the population genetic effects of bacteriophages, specifically, selection for phage resistance mutations, may have caused this. Further mathematical modeling and individual-based simulations supported our hypothesis, showing that conjugative plasmids may hitchhike with phage resistance mutations in the bacterial chromosome.

Importance: Conjugative plasmids are infectious loops of DNA capable of transmitting DNA between bacterial cells and between species. Because plasmids often carry extra genes that allow bacteria to live in otherwise-inhospitable environments, their dynamics are central to understanding bacterial adaptive evolution. The plasmid-bacterium interaction has typically been studied in isolation, but in natural bacterial communities, bacteriophages, viruses that infect bacteria, are ubiquitous. Using experiments, mathematical models, and computer simulations we show that bacteriophages drive plasmid dynamics through their ecological and evolutionary effects on bacteria and ultimately limit the conditions allowing plasmid existence. These results advance our understanding of bacterial adaptation and show that bacteriophages could be used to select against plasmids carrying undesirable traits, such as antibiotic resistance.
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http://dx.doi.org/10.1128/mBio.00586-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453012PMC
June 2015

The evolution of biofilm-forming Wrinkly Spreaders in static microcosms and drip-fed columns selects for subtle differences in wrinkleality and fitness.

FEMS Microbiol Ecol 2015 Jun 21;91(6). Epub 2015 May 21.

SIMBIOS Centre, School of Science, Engineering and Technology, Abertay University, Dundee DD1 1HP, UK

Experimental evolution studies are used to investigate bacterial adaptive radiation in simple microcosms. In the case of the Wrinkly Spreader, a class of biofilm-forming adaptive mutants of Pseudomonas fluorescens SBW25, the current paradigm is that they are only evolutionarily successful in static microcosms where they outcompete other lineages for O2 at the air-liquid interface. However, we have isolated Wrinkly Spreaders from drip-fed glass bead columns as an example of parallel evolution. These mutants are adaptive, with competitive fitness advantages on columns of 1.28-1.78. This might be explained by the enhanced attachment characteristically shown by Wrinkly Spreaders, allowing them to resist liquid flow through the column pore network. A comparison of column and static microcosm-isolated Wrinkly Spreaders showed that many aspects of wrinkleality, including colony reversion, microcosm growth, biofilm strength and attachment, as well as fitness in static microcosms, were significantly different within and between the two groups of mutants. These findings indicate that the two environments had selected for Wrinkly Spreaders with subtly differing degrees of wrinkleality and fitnesses, suggesting that aspects of the Wrinkly Spreader phenotype may have different relative values in static microcosms and drip-fed columns.
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http://dx.doi.org/10.1093/femsec/fiv057DOI Listing
June 2015

Environmentally co-occurring mercury resistance plasmids are genetically and phenotypically diverse and confer variable context-dependent fitness effects.

Environ Microbiol 2015 Dec 25;17(12):5008-22. Epub 2015 Jun 25.

Department of Biology, Wentworth Way, University of York, York, UK.

Plasmids are important mobile elements that can facilitate genetic exchange and local adaptation within microbial communities. We compared the sequences of four co-occurring pQBR family environmental mercury resistance plasmids and measured their effects on competitive fitness of a Pseudomonas fluorescens SBW25 host, which was isolated at the same field site. Fitness effects of carriage differed between plasmids and were strongly context dependent, varying with medium, plasmid status of competitor and levels of environmental mercury. The plasmids also varied widely in their rates of conjugation and segregational loss. We found that few of the plasmid-borne accessory genes could be ascribed functions, although we identified a putative chemotaxis operon, a type IV pilus-encoding cluster and a region encoding putative arylsulfatase enzymes, which were conserved across geographically distant isolates. One plasmid, pQBR55, conferred the ability to catabolize sucrose. Transposons, including the mercury resistance Tn5042, appeared to have been acquired by different pQBR plasmids by recombination, indicating an important role for horizontal gene transfer in the recent evolution of pQBR plasmids. Our findings demonstrate extensive genetic and phenotypic diversity among co-occurring members of a plasmid community and suggest a role for environmental heterogeneity in the maintenance of plasmid diversity.
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http://dx.doi.org/10.1111/1462-2920.12901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989453PMC
December 2015

Transparent soil microcosms allow 3D spatial quantification of soil microbiological processes in vivo.

Plant Signal Behav 2014 ;9(10):e970421

a The James Hutton Institute ; Invergowrie , Dundee , UK.

The recently developed transparent soil consists of particles of Nafion, a polymer with a low refractive index (RI), which is prepared by milling and chemical treatment for use as a soil analog. After the addition of a RI-matched solution, confocal imaging can be carried out in vivo and without destructive sampling. In a previous study, we showed that the new substrate provides a good approximation of plant growth conditions found in natural soils. In this paper, we present further development of the techniques for detailed quantitative analysis of images of root-microbe interactions in situ. Using this system it was possible for the first time to analyze bacterial distribution along the roots and in the bulk substrate in vivo. These findings indicate that the coupling of transparent soil with light microscopy is an important advance toward the discovery of the mechanisms of microbial colonisation of the rhizosphere.
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http://dx.doi.org/10.4161/15592316.2014.970421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622970PMC
August 2015

Getting Wrinkly Spreaders to demonstrate evolution in schools.

Authors:
Andrew J Spiers

Trends Microbiol 2014 Jun;22(6):301-3

SIMBIOS Centre and School of Science, Engineering, and Technology, Abertay University, Bell Street, Dundee, DD1 1HG, UK. Electronic address:

Understanding evolution is crucial to modern biology, but most teachers would assume that practical demonstrations of evolution in school laboratories are unfeasible. However, perhaps they have not heard of 'evolution in a test tube' and how Wrinkly Spreaders can form the basis for both practical demonstrations of bacterial evolution and further work.
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http://dx.doi.org/10.1016/j.tim.2014.03.007DOI Listing
June 2014

A mechanistic explanation linking adaptive mutation, niche change, and fitness advantage for the wrinkly spreader.

Authors:
Andrew J Spiers

Int J Evol Biol 2014 16;2014:675432. Epub 2014 Jan 16.

The SIMBIOS Centre & School of Science, Engineering and Technology, Abertay University, Bell Street, Dundee DD1 1HG, UK.

Experimental evolution studies have investigated adaptive radiation in static liquid microcosms using the environmental bacterium Pseudomonas fluorescens SBW25. In evolving populations a novel adaptive mutant known as the Wrinkly Spreader arises within days having significant fitness advantage over the ancestral strain. A molecular investigation of the Wrinkly Spreader has provided a mechanistic explanation linking mutation with fitness improvement through the production of a cellulose-based biofilm at the air-liquid interface. Colonisation of this niche provides greater access to oxygen, allowing faster growth than that possible for non-biofilm-forming competitors located in the lower anoxic region of the microcosm. Cellulose is probably normally used for attachment to plant and soil aggregate surfaces and to provide protection in dehydrating conditions. However, the evolutionary innovation of the Wrinkly Spreader in static microcosms is the use of cellulose as the matrix of a robust biofilm, and is achieved through mutations that deregulate multiple diguanylate cyclases leading to the over-production of cyclic-di-GMP and the stimulation of cellulose expression. The mechanistic explanation of the Wrinkly Spreader success is an exemplar of the modern evolutionary synthesis, linking molecular biology with evolutionary ecology, and provides an insight into the phenomenal ability of bacteria to adapt to novel environments.
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http://dx.doi.org/10.1155/2014/675432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914426PMC
June 2014

Transparent soil for imaging the rhizosphere.

PLoS One 2012 11;7(9):e44276. Epub 2012 Sep 11.

The James Hutton Institute, Invergowrie, Dundee, United Kingdom.

Understanding of soil processes is essential for addressing the global issues of food security, disease transmission and climate change. However, techniques for observing soil biology are lacking. We present a heterogeneous, porous, transparent substrate for in situ 3D imaging of living plants and root-associated microorganisms using particles of the transparent polymer, Nafion, and a solution with matching optical properties. Minerals and fluorescent dyes were adsorbed onto the Nafion particles for nutrient supply and imaging of pore size and geometry. Plant growth in transparent soil was similar to that in soil. We imaged colonization of lettuce roots by the human bacterial pathogen Escherichia coli O157:H7 showing micro-colony development. Micro-colonies may contribute to bacterial survival in soil. Transparent soil has applications in root biology, crop genetics and soil microbiology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0044276PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439476PMC
March 2013

Air-liquid interface biofilm formation by psychrotrophic pseudomonads recovered from spoilt meat.

Antonie Van Leeuwenhoek 2013 Jan 16;103(1):251-9. Epub 2012 Sep 16.

The SIMBIOS Centre & School of Contemporary Sciences, University of Abertay Dundee, Bell Street, Dundee, DD1 1HG, UK.

The ability to colonise the surface of liquids has obvious advantages for bacteria and biofilm formation at the meniscus and air-liquid (A-L) interface is common amongst environmental pseudomonads. Bacteria from this genus also colonise raw meat and in this work the ability of these to produce biofilms was assessed. Sixty isolates were recovered from vacuum-packed venison, phenotypically characterised and shown by hierarchical cluster analysis to represent a diverse collection of psychrotrophic spoilt venison-associated pseudomonads. Of these, 12 % were found to produce biofilms limited to the meniscus region of the microcosm walls, 31 % produced attached biofilms with significant extensions across the A-L interface and 45 % produced unattached 'floating' biofilms. A combined statistical analysis of growth, biofilm strength and attachment levels revealed that growth affected strength but not attachment, and that there was a significant relationship between attachment and strength. Some environmental pseudomonads are known to utilise cellulose as a biofilm matrix component and here 28 % of the SVP isolates were found to express cellulose by epifluorescent microscopy. This survey suggests that biofilm formation may be more common in psychrotrophic meat-associated isolates than amongst the wider pseudomonad community from which spoilage bacteria might be recruited. This may reflect a selective advantage of bacterial aggregations such as biofilms in environments subject to high levels of physical disturbance. Aggregations may be more resistant to competition and dehydration stress than individual bacteria, whilst fragments of these aggregations may prove more effective in the colonisation of new habitats.
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http://dx.doi.org/10.1007/s10482-012-9796-xDOI Listing
January 2013

Surfactants expressed by soil pseudomonads alter local soil-water distribution, suggesting a hydrological role for these compounds.

FEMS Microbiol Ecol 2011 Oct 28;78(1):50-8. Epub 2011 Jun 28.

The SIMBIOS Centre and the School of Contemporary Sciences, University of Abertay Dundee, Dundee, UK.

Several biological roles have been demonstrated for surfactants expressed by soil and rhizosphere Pseudomonas spp., but the impact of these powerful surface-active agents on the local soil-water distribution within the partially saturated soil pore network has not been examined. To investigate this potential hydrological role, the liquid surface tension (γ)-reducing activities (LSTRA) of 72 pseudomonads isolated from a sandy loam soil by tensiometry of culture supernatants were characterized. Of these, 67% exhibited LSTRA, reducing γ to a minimum (γ(Min)) of 24 mN m(-1) established by individual distribution identification analysis. Soil microcosms were then used to examine the impact of surfactant expression on the local soil-water distribution. The volumetric water content (θ) of soil microcosms was significantly lowered (0.78 ×) by Pseudomonas fluorescens SBW25 expressing the surfactant viscosin compared with a surfactant-deficient mutant (P<0.002). Six of 15 soil pseudomonad isolates examined were found to have a similar impact on θ when compared with sterile microcosms (P<0.05). These findings indicate that surfactant-expressing pseudomonads could modify the local soil-water distributions and that surfactants may therefore play a significant hydrological role in soils, in addition to their recognized biological activities.
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http://dx.doi.org/10.1111/j.1574-6941.2011.01141.xDOI Listing
October 2011