Publications by authors named "Karen A Krogfelt"

153 Publications

Trained immunity in viral infections, Alzheimer's disease and multiple sclerosis: A convergence in type I interferon signalling and IFNβ-1a.

Biochim Biophys Acta Mol Basis Dis 2022 May 10;1868(9):166430. Epub 2022 May 10.

Department Neurology, University of Cyprus, Lefkosia, Cyprus. Electronic address:

Type I interferon (IFN-I) signalling represents a major target for modulation in a virus' bid for latency. IFN-I perturbations are also present in such as Alzheimer's disease (AD) and multiple sclerosis (MS), where viral infections are known to increase symptomatic burden. IFN-I modulation such as via IFNβ-1a, an established MS treatment, has been researched to a limited extent to both AD and COVID-19. In this mini review, we present emerging research on trained immunity as a pathogenetic basis for Alzheimer's disease and the emerging context for IFNβ-1a repositioning, via mechanisms shared with multiple sclerosis and induced by viral infections.
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http://dx.doi.org/10.1016/j.bbadis.2022.166430DOI Listing
May 2022

Distribution of serotypes and antibiotic resistance of invasive Pseudomonas aeruginosa in a multi-country collection.

BMC Microbiol 2022 01 6;22(1):13. Epub 2022 Jan 6.

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St. - HSF1 Room 480, Baltimore, MD, 21201, USA.

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005-2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and antibiotic susceptibility of the invasive P. aeruginosa. We used an antibody-based agglutination assay and PCR for O antigen typing and PCR for flagellin typing. We determined antibiotic susceptibility using the Kirby-Bauer disk diffusion method.

Results: Of the 413 isolates, 314 (95%) were typed by an antibody-based agglutination assay or PCR (n = 99). Among the 20 serotypes of P. aeruginosa, the most common serotypes were O1, O2, O3, O4, O5, O6, O8, O9, O10 and O11; a vaccine that targets these 10 serotypes would confer protection against more than 80% of invasive P. aeruginosa infections. The most common flagellin type among 386 isolates was FlaB (41%). Resistance to aztreonam (56%) was most common, followed by levofloxacin (42%). We also found that 22% of strains were non-susceptible to meropenem and piperacillin-tazobactam. Ninety-nine (27%) of our collected isolates were resistant to multiple antibiotics. Isolates with FlaA2 flagellin were more commonly multidrug resistant (p = 0.04).

Conclusions: Vaccines targeting common O antigens and two flagellin antigens, FlaB and FlaA2, would offer an excellent strategy to prevent P. aeruginosa invasive infections.
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http://dx.doi.org/10.1186/s12866-021-02427-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732956PMC
January 2022

Tick-transmitted co-infections among erythema migrans patients in a general practice setting in Norway: a clinical and laboratory follow-up study.

BMC Infect Dis 2021 Oct 8;21(1):1044. Epub 2021 Oct 8.

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, 58185, Linköping, Sweden.

Background: Erythema migrans (EM) is the most common manifestation of Lyme borreliosis. Here, we examined EM patients in Norwegian general practice to find the proportion exposed to tick-transmitted microorganisms other than Borrelia, and the impact of co-infection on the clinical manifestations and disease duration.

Methods: Skin biopsies from 139/188 EM patients were analyzed using PCR for Neoehrlichia mikurensis, Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Follow-up sera from 135/188 patients were analyzed for spotted fever group (SFG) Rickettsia, A. phagocytophilum and Babesia microti antibodies, and tested with PCR if positive. Day 0 sera from patients with fever (8/188) or EM duration of ≥ 21 days (69/188) were analyzed, using PCR, for A. phagocytophilum, Rickettsia spp., Babesia spp. and N. mikurensis. Day 14 sera were tested for TBEV IgG.

Results: We detected no microorganisms in the skin biopsies nor in the sera of patients with fever or prolonged EM duration. Serological signs of exposure against SFG Rickettsia and A. phagocytophilum were detected in 11/135 and 8/135, respectively. Three patients exhibited both SFG Rickettsia and A. phagocytophilum antibodies, albeit negative PCR. No antibodies were detected against B. microti. 2/187 had TBEV antibodies without prior immunization. There was no significant increase in clinical symptoms or disease duration in patients with possible co-infection.

Conclusions: Co-infection with N. mikurensis, A. phagocytophilum, SFG Rickettsia, Babesia spp. and TBEV is uncommon in Norwegian EM patients. Despite detecting antibodies against SFG Rickettsia and A. phagocytophilum in some patients, no clinical implications could be demonstrated.
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http://dx.doi.org/10.1186/s12879-021-06755-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501555PMC
October 2021

New Insights into the Antimicrobial Action of Cinnamaldehyde towards and Its Effects on Intestinal Colonization of Mice.

Biomolecules 2021 02 18;11(2). Epub 2021 Feb 18.

Laboratório de Patogenicidade Microbiana, Programa de Pós-Graduação em Biologia Microbiana, Universidade Ceuma, São Luís 65075-120, Brazil.

is responsible for cases of diarrhea around the world, and some studies have shown the benefits of cinnamaldehyde in the treatment of bacterial disease. Therefore, the objective of this study was to evaluate the effects of cinnamaldehyde in mice colonized by pathogenic , as well as to provide more insights into its antimicrobial action mechanism. After determination of minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations, the interference of cinnamaldehyde in macromolecular pathways (synthesis of DNA, RNA, protein, and cell wall) was measured by incorporation of radioisotopes. The anti-adhesive properties of cinnamaldehyde towards 042 were evaluated using human epithelial type 2 (HEp-2) cells. Intestinal colonization was tested on mice, and the effect of cinnamaldehyde on larvae. Cinnamaldehyde showed MIC and MBC values of 780 μg/mL and 1560 μg/mL, respectively; reduced the adhesion of 042 on HEp-2 cells; and affected all the synthetic pathways evaluated, suggesting that compost impairs the membrane/cell wall structure leading bacteria to total collapse. No effect on the expression of genes related to the SOS pathway ( and ) was observed. The compound did not interfere with cell viability and was not toxic against larvae. In addition, cinnamaldehyde-treated mice exhibited lower levels of colonization by 042 than the untreated group. Therefore, the results show that cinnamaldehyde is effective in treating the pathogenic strain 042 and confirm it as a promising lead molecule for the development of antimicrobial agents.
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http://dx.doi.org/10.3390/biom11020302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922552PMC
February 2021

How can we interpret SARS-CoV-2 antibody test results?

Pathog Dis 2021 02;79(1)

Roskilde University, Department of Science and Environment, Universitetsvej 1, Roskilde, Denmark.

Since the outbreak of COVID-19, the world has raced to understand and accurately diagnose infection caused by SARS-CoV-2. Today, hundreds of commercial antibody tests are on the market despite often lacking proper validation and with unsatisfactory sensitivity and/or specificity. In addition, many questions related to the humoral response remain unresolved, although research is carried out at an unprecedented speed. Despite the shortcomings, serological assays have an important part to play in combating the pandemic by aiding in diagnosis and sero-epidemiological studies. However, careful attention must be paid to the application of serology and the interpretation of serological data-especially in low prevalence regions, both at an individual and at a population level. In this article, we argue that serological results are often misinterpreted, and in the eagerness to be first, methodological rigor is often taking a backseat.
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http://dx.doi.org/10.1093/femspd/ftaa069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858042PMC
February 2021

FUT2-ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses.

Nat Commun 2020 12 16;11(1):6398. Epub 2020 Dec 16.

Department of Human Genetics, University of Chicago, Chicago, IL, USA.

Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11-1.25), P = 2.6 × 10) as well as a biologically plausible interaction between functional variants in FUT2 and ABO. We further discover and replicate a potential causal mechanism behind this interaction related to S. pneumoniae respiratory illnesses. These results suggest a novel mechanism of early childhood asthma and demonstrates the importance of phenotype-specificity for discovery of asthma genes and epistasis.
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http://dx.doi.org/10.1038/s41467-020-19814-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744576PMC
December 2020

Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark.

JAMA Psychiatry 2021 02;78(2):177-186

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Importance: The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate.

Objective: To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort.

Design, Setting, And Participants: This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020.

Exposures: Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi.

Main Outcomes And Measures: The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort.

Results: Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort.

Conclusions And Relevance: In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542530PMC
February 2021

Changes in Lyme neuroborreliosis incidence in Denmark, 1996 to 2015.

Ticks Tick Borne Dis 2020 11 25;11(6):101549. Epub 2020 Aug 25.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Lyme neuroborreliosis (LNB) has recently been added to the list of diseases under the European Union epidemiological surveillance in order to obtain updated information on incidence. The goal of this study was to identify temporal (yearly) variation, high risk geographical regions and risk groups, and seasonal variation for LNB in Denmark. This cohort-study investigated Danish patients (n = 2791) diagnosed with LNB (defined as a positive Borrelia burgdorferi sensu lato (s.l.) intrathecal antibody test) between 1996-2015. We calculated incidence and incidence ratios of LNB by comparing 4-yr groups of calendar-years, area of residency, sex and age, income and education groups, and the number of new LNB cases per month. The incidence of LNB was 2.2 per 100,000 individuals and year in 1996-1999, 2.7 in 2004-2007 and 1.1 per 100,000 individuals in 2012-2015. Yearly variations in LNB incidence were similar for most calendar-year groups. LNB incidence was highest in Eastern Denmark and among males and individuals who were 0-14 yrs old, who had a yearly income of >449,000 DKK, and who had a Master's degree or higher education. The number of LNB cases was highest from July to November (p < 0.001). In conclusion, based on Danish nationwide data of patients with positive B. burgdorferi s.l. intrathecal antibody index (1996-2015) the incidence of LNB was found to increase until 2004-2007 but thereafter to decline. European surveillance studies of Lyme borreliosis should be encouraged to monitor the incidence trend.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101549DOI Listing
November 2020

Spatial tick bite exposure and associated risk factors in Scandinavia.

Infect Ecol Epidemiol 2020 Jun 7;10(1):1764693. Epub 2020 Jun 7.

Department of Infection Prevention & Preparedness, Norwegian Public Health Institute, Oslo, Norway.

Tick-borne diseases are emerging and re-emerging threats causing public health concerns in Europe and North America. Prevention and control requires understanding of human exposure and behaviour. The aim was to measure exposure to tick bites across Scandinavia, its spatial distribution and the associated risk factors. Methods We sent a web-based survey to a randomly chosen population and analysed answers by Principal Component Analysis and Chi-Square. Individual responses were aggregated at the municipality level to assess the spatial distribution of bites. Results Nearly 60% of adults reported bites at low levels (1-5 bites); however, the majority were not in their resident municipality. We found two spatial profiles: In their home municipalities, people were most often bitten in less, but not the least, urbanized areas. When visiting other municipalities, people were most frequently bitten in peri-urban areas. Running/walking in the forest, gardening, and paddling/rowing were activities most strongly associated with bites. Conclusion Tick bites affect the entire Scandinavian population, with a higher risk in Sweden compared to Denmark and Norway. The frequency of observation of ticks in the environment or on pets might be used as a proxy for the actual risk of exposure to tick bites. Our results indicates that urban-dwelling outdoor enthusiasts and inhabitants of rural areas must be equally targeted for prevention campaigns.
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http://dx.doi.org/10.1080/20008686.2020.1764693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448850PMC
June 2020

Epigenetic regulation of apoptosis via the PARK7 interactome in peripheral blood mononuclear cells donated by tuberculosis patients vs. healthy controls and the response to treatment: A systems biology approach.

Tuberculosis (Edinb) 2020 07 31;123:101938. Epub 2020 May 31.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Mezourlo, 41110, Larisa, Greece.

Aims: The aims of our study were to determine for the first time differentially expressed genes (DEGs) and enriched molecular pathways involving the PARK7 interactome in PBMCs donated from tuberculosis patients.

Methods: Data on a previously reconstructed PARK7 interactome (Vavougios et al., 2017) from datasets GDS4966 (Case-Control) and GDS4781 (Treatment Series) were retrieved from the Gene Expression Omnibus (GEO) repository. Gene Enrichment analysis was performed via the STRING algorithm and the GeneTrail2 software.

Results: 17 and 22 PARK7 interactores were determined as DEGs in the active TB vs HD and Treatment Series subset analyses, correspondingly, associated with significantly enriched pathways (FDR <0.05) involving p53 and PTEN mediated, stress responsive apoptosis regulation pathways. The treatment subset was characterized by the emergence of an additional layer of transcriptional regulation mediated by polycomb proteins among others, as well as TLR-mediated and cytokine survival signaling. Finally, the enrichment of a Parkinson's disease signature including PARK7 interactors was determined by its differential regulation both in the exploratory analyses (FDR = 0.024), as well as the confirmatory analyses (FDR = 1.81e).

Conclusions: Our in silico analysis revealed for the first time the role of PARK7's interactome in regulating the epigenetics of the PBMC lifecycle and Mtb symbiosis.
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http://dx.doi.org/10.1016/j.tube.2020.101938DOI Listing
July 2020

Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis.

Microorganisms 2020 Jul 9;8(7). Epub 2020 Jul 9.

The Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, Denmark.

(1) Background: Persistent infection is the most important risk factor for gastric cancer. The urokinase receptor (uPAR) is upregulated in lesions harboring cancer invasion and inflammation. Circumstantial evidence tends to correlate colonization with increased uPAR expression in the human gastric epithelium, but a direct causative link has not yet been established in vivo; (2) Methods: In a mouse model of -induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to (SS1 strain) infection; (3) Results: We observed intense uPAR immunoreactivity in foveolar epithelial cells of the gastric corpus due to de novo synthesis, compared to non-infected animals. This uPAR induction represents a very early response, but it increases progressively over time as do infiltrating immune cells. Eradication of infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E treatment attenuates uPAR expression. Notwithstanding this relationship, does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells.
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http://dx.doi.org/10.3390/microorganisms8071019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409347PMC
July 2020

Laboratory Diagnostics of Infections in Denmark 2008-2015.

Biology (Basel) 2020 Jun 19;9(6). Epub 2020 Jun 19.

Department of Bacteria, Parasites and Fungi, Statens Serum Institut (SSI), 2300 Copenhagen, Denmark.

Rickettsiosis is a vector-borne disease caused by bacterial species in the genus . Ticks in Scandinavia are reported to be infected with , yet only a few Scandinavian human cases are described, and rickettsiosis is poorly understood. The aim of this study was to determine the prevalence of rickettsiosis in Denmark based on laboratory findings. We found that in the Danish individuals who tested positive for by serology, the majority (86%; 484/561) of the infections belonged to the spotted fever group. In contrast, we could confirm 13 of 41 (32%) PCR-positive individuals by sequencing and identified all of these as , indicating infections after travel exposure. These 13 samples were collected from wound/skin material. In Denmark, approximately 85 individuals test positive for spp. annually, giving an estimated 26% (561/2147) annual prevalence among those suspected of rickettsiosis after tick bites. However, without clinical data and a history of travel exposure, a true estimation of rickettsiosis acquired endemically by tick bites cannot be made. Therefore, we recommend that both clinical data and specific travel exposure be included in a surveillance system of infections.
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http://dx.doi.org/10.3390/biology9060133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345066PMC
June 2020

Emergence of Enteroaggregative Escherichia coli within the ST131 Lineage as a Cause of Extraintestinal Infections.

mBio 2020 05 19;11(3). Epub 2020 May 19.

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark

sequence type 131 (ST131) is a major cause of urinary and bloodstream infections. Its association with extended-spectrum β-lactamases (ESBLs) significantly complicates treatment. Its best-described component is the rapidly expanding 30Rx clade, containing allele 30 of the type 1 fimbrial adhesin gene This lineage appears to have emerged in the United States and spread around the world in part due to the acquisition of the ESBL-encoding gene and resistance to fluoroquinolones. However, non-30 ST131 sublineages with other acquired CTX-M-type resistance genes are also emerging. Based on whole-genome analyses, we describe here the presence of an () 27 ST131 sublineage that has recently caused an outbreak of community-acquired bacteremia and recurrent urinary tract infections (UTIs) in Denmark. This sublineage has acquired both a virulence plasmid (pAA) that defines the enteroaggregative (EAEC) diarrheagenic pathotype and multiple genes associated with extraintestinal (ExPEC); combined, these traits have made this particular ST131 sublineage successful at colonizing its human host and causing recurrent UTI. Moreover, using a historic World Health Organization (WHO) collection and publicly available genome sequences, we identified a global 27 EAEC ST131 sublineage that dates back as far as 1998. Most 27 EAEC ST131 isolates harbor pAA or pAA-like plasmids, and our analysis strongly implies a single ancestral acquisition among these isolates. These findings illustrate both the profound plasticity of this important pathogenic ST131 27 sublineage and genetic acquisitions of EAEC-specific virulence traits that likely confer an enhanced ability to cause intestinal colonization. ST131 is an important extraintestinal pathogenic lineage. A signature characteristic of ST131 is its ability to asymptomatically colonize the gastrointestinal tract and then opportunistically cause extraintestinal infections, such as cystitis, pyelonephritis, and urosepsis. In this study, we identified an ST131 27 sublineage that has acquired the enteroaggregative diarrheagenic phenotype, spread across multiple continents, and caused multiple outbreaks of community-acquired ESBL-associated bloodstream infections in Denmark. The strain's ability to both cause diarrhea and innocuously colonize the human gastrointestinal tract may facilitate its dissemination and establishment in the community.
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http://dx.doi.org/10.1128/mBio.00353-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240153PMC
May 2020

Virulent coliphages in 1-year-old children fecal samples are fewer, but more infectious than temperate coliphages.

Nat Commun 2020 01 17;11(1):378. Epub 2020 Jan 17.

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France.

Bacteriophages constitute an important part of the human gut microbiota, but their impact on this community is largely unknown. Here, we cultivate temperate phages produced by 900 E. coli strains isolated from 648 fecal samples from 1-year-old children and obtain coliphages directly from the viral fraction of the same fecal samples. We find that 63% of strains hosted phages, while 24% of the viromes contain phages targeting E. coli. 150 of these phages, half recovered from strain supernatants, half from virome (73% temperate and 27% virulent) were tested for their host range on 75 E. coli strains isolated from the same cohort. Temperate phages barely infected the gut strains, whereas virulent phages killed up to 68% of them. We conclude that in fecal samples from children, temperate coliphages dominate, while virulent ones have greater infectivity and broader host range, likely playing a role in gut microbiota dynamics.
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http://dx.doi.org/10.1038/s41467-019-14042-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969025PMC
January 2020

Risk of Neurological Disorders in Patients With European Lyme Neuroborreliosis: A Nationwide, Population-Based Cohort Study.

Clin Infect Dis 2020 09;71(6):1511-1516

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Lyme neuroborreliosis (LNB), caused by the tick-borne spirochetes of the Borrelia burgdorferi sensu lato species complex, has been suggested to be associated with a range of neurological disorders. In a nationwide, population-based cohort study, we examined the associations between LNB and dementia, Alzheimer's disease, Parkinson's disease, motor neuron disease, epilepsy, and Guillain-Barré syndrome.

Methods: We used national registers to identify all Danish residents diagnosed during 1986-2016 with LNB (n = 2067), created a gender- and age-matched comparison cohort from the general population (n = 20 670), and calculated risk estimates and hazard ratios.

Results: We observed no long-term increased risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, or epilepsy. However, within the first year, 8 (0.4%) of the LNB patients developed epilepsy, compared with 20 (0.1%) of the comparison cohort (difference, 0.3%; 95% confidence interval, .02-.6%). In the LNB group, 11 (0.5%) patients were diagnosed with Guillain-Barré syndrome within the first year after LNB diagnosis, compared with 0 (0.0%) in the comparison cohort. After the first year, the risk of Guillain-Barré was not increased.

Conclusions: LNB patients did not have increased long-term risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, epilepsy, or Guillain-Barré. Although the absolute risk is low, LNB patients might have an increased short-term risk of epilepsy and Guillain-Barré syndrome.
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http://dx.doi.org/10.1093/cid/ciz997DOI Listing
September 2020

Amplicon sequencing provides more accurate microbiome information in healthy children compared to culturing.

Commun Biol 2019 5;2:291. Epub 2019 Aug 5.

1Section of Microbiology, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.

Next-Generation Sequencing (NGS) of 16S rRNA gene is now one of the most widely used application to investigate the microbiota at any given body site in research. Since NGS is more sensitive than traditional culture methods (TCMs), many studies have argued for them to replace TCMs. However, are we really ready for this transition? Here we compare the diagnostic efficiency of the two methods using a large number of samples ( = 1,748 fecal and  = 1,790 hypopharyngeal), among healthy children at different time points. Here we show that bacteria identified by NGS represented 75.70% of the unique bacterial species cultured in each sample, while TCM only identified 23.86% of the bacterial species found by amplicon sequencing. We discuss the pros and cons of both methods and provide perspective on how NGS can be implemented effectively in clinical settings.
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http://dx.doi.org/10.1038/s42003-019-0540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683184PMC
April 2020

Persistence of antibodies to pneumococcal conjugate vaccine compared to polysaccharide vaccine in patients with Crohn's disease - one year follow up.

Infect Dis (Lond) 2019 09 10;51(9):651-658. Epub 2019 Jul 10.

b Department of Gastroenterology, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark.

Patients suffering from Crohn's disease (CD) are at increased risk of infectious diseases, such as pneumococcal infection. The risk increases with immunotherapy. Pneumococcal infection can be prevented by vaccination. We conducted a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13) in groups of CD patients treated with immunosuppressive (IS) drugs in the form of thiopurines (PPV23  = 28, PCV13  = 28) alone or in combination with TNF-α antagonists (PPV23  = 13, PCV13  = 13) and CD patients not treated with any of these drugs (untreated) (PPV23  = 30, PCV13  = 24). In this article, we report the immunogenicity of PPC23 and PCV13 one year after vaccination. No overall differences in vaccine-induced serotype-specific immunoglobulin G (IgG) antibodies or functional antibodies (opsonophagocytic activity (OPA)) were found between the two vaccines. PCV13 induced a higher concentration of IgG antibodies for serotype 9V than PPV23 in untreated patients. In contrast, PPV23 induced higher OPA for serotypes 6B and 19F than PCV13 in IS treated patients. Untreated patients showed generally higher IgG and OPA antibody levels than patients treated with IS and TNF-α antagonists. In conclusion, we found no general differences in the persistence of induced antibodies when comparing PPV23 with PCV13 regardless of treatment and also within treatment groups (IS, IS + TNF-α and untreated). This was demonstrated for both serotype-specific IgG antibodies and as functional antibodies (OPA). Patients treated with thiopurines in combination with TNF-α inhibitors have an impaired immune response against both PPV23 and PCV13, as compared to untreated patients. This study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).
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http://dx.doi.org/10.1080/23744235.2019.1638519DOI Listing
September 2019

Impact of Early Exposure to Cefuroxime on the Composition of the Gut Microbiota in Infants Following Cesarean Delivery.

J Pediatr 2019 07 30;210:99-105.e2. Epub 2019 Apr 30.

Department of Food Science, University of Copenhagen, Frederiksberg, Denmark. Electronic address:

Objectives: To assess in mothers giving birth by cesarean delivery if prophylactic antibiotics administered either before skin incision or immediately after cutting the umbilical cord influences gut microbiota colonization and antibiotic susceptibility of the gut bacteria in the newborn.

Study Design: Forty-two pregnant women scheduled for elective cesarean delivery were recruited at Odense University Hospital, Denmark, and randomly assigned to receive cefuroxime either before skin incision or immediately after the umbilical cord was cut. Fecal samples were collected from all infants at age 10 days and 9 months. Composition of the gut microbiota was determined by 16S ribosomal RNA gene amplicon high-throughput sequencing. Gram-positive cocci and Enterobacteriaceae were isolated and identified before antimicrobial susceptibility tests were performed by disk diffusion.

Results: No clear difference in the composition of the gut microbiota was observed between infants whose mothers received cefuroxime before or after cesarean delivery at neither time point, though surprisingly at 9 months of age, but not at 10 days of age, the number of observed species was higher in infants where mothers received cefuroxime after cord clamping. No differences in antimicrobial susceptibility of Enterobacteriaceae, Enterococcus spp, and Staphylococcus spp were seen at 10 days.

Conclusions: Timing of cefuroxime administration to mothers undergoing cesarean delivery does not have a major effect on the gut microbiota and bacterial antibiotic resistance traits in infants.

Trial Registration: Clinicaltrials.gov: NCT02072798.
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http://dx.doi.org/10.1016/j.jpeds.2019.03.001DOI Listing
July 2019

Molecular characterization and epidemiology of Streptococcus pneumoniae serotype 24F in Denmark.

Sci Rep 2019 04 2;9(1):5481. Epub 2019 Apr 2.

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.

Since 2012, have we in Denmark observed an increase of invasive pneumococcal infections (IPD) due to Streptococcus pneumoniae serotype 24F. We here present epidemiological data on 24F IPD cases, and characterization of 48 24F clinical isolates based on clonal relationship, antimicrobial resistance (AMR) determinants and virulence factors. IPD surveillance data from (1999-2016) were used to calculate the incidence and age-distribution of serotype 24F IPD and the effect of pneumococcal conjugated vaccines (PCV). Characterization of forty-eight 24F isolates (14.7% of all 24F isolates from the period) was based on whole-genome sequencing analysis (WGS). The IPD cases of serotype 24F showed a significant increase (p < 0.05) for all age groups after the PCV-13 introduction in 2010. The majority of tested 24F isolates consisted of two MLST types, i.e. the ST72 and the ST162. Serotype 24F IPD increased in Denmark after the PCV-13 introduction in parallel with an increase of the ST162 clone. The genotypic penicillin binding protein (PBP) profile agreed with the phenotypical penicillin susceptibility. The virulence genes lytA, ply, piaA, piaB, piaC, rspB and the cpsA/wzg were detected in all 24F isolates, while the pspA and zmpC genes were absent.
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http://dx.doi.org/10.1038/s41598-019-41983-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445336PMC
April 2019

Children Attending Day Care Centers are a Year-round Reservoir of Gastrointestinal Viruses.

Sci Rep 2019 03 1;9(1):3286. Epub 2019 Mar 1.

Statens Serum Institut, Department of Bacteria, Parasites and Fungi, Copenhagen, Denmark.

Viral gastroenteritis causes high morbidity worldwide. In this study, stool samples from 179 children aged 0-6 years attending Danish day care centers were investigated for gastrointestinal viruses. Each child was observed for one year with submission of samples and questionnaires every two months. Adenovirus, norovirus, rotavirus, and sapovirus were detected in samples using real-time PCR. A total of 229 (33%) of the 688 samples collected tested positive for at least one virus. At the first sampling point, adenovirus was shed by 6%, norovirus genotype I by 3% and genotype II by 12%, rotavirus A by 9%, and sapovirus by 21% of the 142 children included in the risk factor analyses. Increasing age was identified as a protective factor against testing positive for gastrointestinal virus, whereas nausea during the previous two months was positively associated with testing positive. Odds of shedding adenovirus were 9.6 times higher among children treated with antibiotics within the previous two months than among children who were not. Gastrointestinal viruses were shed year-round and high viral loads were observed in samples from both symptomatic and asymptomatic children, suggesting children in day care as a reservoir and a possible source of spreading of viruses into the community.
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http://dx.doi.org/10.1038/s41598-019-40077-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397223PMC
March 2019

A Simple Gut Model for Studying the Interaction between Escherichia coli and the Intestinal Commensal Microbiota in Cecal Mucus.

Appl Environ Microbiol 2018 12 30;84(24). Epub 2018 Nov 30.

Department of Cell and Molecular Biology, University of Rhode Island, Kingston, Rhode Island, USA

A novel gut model was developed to better understand the interactions between and the mouse cecal mucus commensal microbiota. The gut model is simple and inexpensive while providing an environment that largely replicates the nonadherent mucus layer of the mouse cecum. 16S rRNA gene profiling of the cecal microbial communities of streptomycin-treated mice colonized with MG1655 or Nissle 1917 and the gut model confirmed that the gut model properly reflected the community structure of the mouse intestine. Furthermore, the results from the gut model mimic the results of published competitive colonization experiments. The gut model is initiated by the colonization of streptomycin-treated mice, and then the community is serially transferred in microcentrifuge tubes in an anaerobic environment generated in anaerobe jars. The nutritional makeup of the cecum is simulated in the gut model by using a medium consisting of porcine mucin, mouse cecal mucus, HEPES-Hanks buffer (pH 7.2), Cleland's reagent, and agarose. Agarose was found to be essential for maintaining the stability of the microbial community in the gut model. The outcome of competitions between strains in the gut model is readily explained by the "restaurant hypothesis" of intestinal colonization. This simple model system potentially can be used to more fully understand how different members of the microbiota interact physically and metabolically during the colonization of the intestinal mucus layer. Both commensal and pathogenic strains of appear to colonize the mammalian intestine by interacting physically and metabolically with other members of the microbiota in the mucus layer that overlays the cecal and colonic epithelium. However, the use of animal models and the complexity of the mammalian gut make it difficult to isolate experimental variables that might dictate the interactions between and other members of the microbiota, such as those that are critical for successful colonization. Here, we describe a simple and relatively inexpensive gut model that largely mimics conditions and therefore can facilitate the manipulation of experimental variables for studying the interactions of with the intestinal microbiota.
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http://dx.doi.org/10.1128/AEM.02166-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275339PMC
December 2018

Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study.

BMJ 2018 05 30;361:k1998. Epub 2018 May 30.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, DK-2100, Copenhagen, Denmark.

Objective: To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.

Design: Nationwide population based cohort study using national registers.

Setting: Denmark.

Participants: All Danish residents diagnosed during 1986-2016 as having Lyme neuroborreliosis (n=2067), defined as a positive intrathecal antibody test and a clinical diagnosis of Lyme borreliosis, and a comparison cohort from the general population matched on sex and date of birth (n=20 670).

Main Outcome Measures: Mortality rate ratios, incidence rate ratios of comorbidities, and differences in educational and social outcomes.

Results: Mortality among patients with Lyme neuroborreliosis was not higher than in the general population (mortality rate ratio 0.90, 95% confidence interval 0.79 to 1.03). Lyme neuroborreliosis patients had increased risk of haematological (incidence rate ratio 3.07, 2.03 to 4.66) and non-melanoma skin cancers (1.49, 1.18 to 1.88). At diagnosis, Lyme neuroborreliosis patients had slightly higher employment and lower disability pension rates. After five years, patients and comparison cohort members had similar numbers of hospital contacts (difference -0.22, 95% confidence interval -0.45 to 0.02, in-hospital days/year; 0.37, -0.10 to 0.83, outpatient visits/year), employment rates (difference 1.5%, -2.1% to 5.1%), income (difference -1000, -20 000 to 18 000, Danish kroner), days of sick leave (difference -0.3, -3.5 to 3.0, per year), rates of receipt of a disability pension (difference -0.9%, -3.2% to 1.3%), and number of children (difference -0.10, -0.27 to 0.08). More patients were married (difference 4.8%, 2.2% to 7.4%) and had completed high school education (difference 7%, 1% to 12%).

Conclusion: A verified diagnosis of Lyme neuroborreliosis had no substantial effect on long term survival, health, or educational/social functioning. Nevertheless, the diagnosis decreased labour market involvement marginally and was associated with increased risk of haematological and non-melanoma skin cancers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974636PMC
http://dx.doi.org/10.1136/bmj.k1998DOI Listing
May 2018

Identification of a prospective early motor progression cluster of Parkinson's disease: Data from the PPMI study.

J Neurol Sci 2018 04 31;387:103-108. Epub 2018 Jan 31.

Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Second Department of Neurology, National and Kapodistrian University of Athens Medical School, Athens, Greece.

Aim: The aim of our study is to phenotype PD motor progression, and to detect whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and neuropsychological measures characterize PD motor progression phenotypes.

Methods: We defined motor progression as a difference of at least one point in the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit 04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers Initiative (PPMI) study. H&Y progression events were recorded at each milestone in order to be used as cluster analysis variables, in order to produce progression phenotypes. Subsequently, cross-cluster comparisons prior to and following (pairwise) propensity score matching were performed in order to assess phenotype - defining characteristics.

Results: Four progression clusters where identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as statistically significant cross-cluster characteristics. Following Propensity Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1, CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line Orientation Test (BJLOT) were determined as statistically significant predictors of cluster differentiation (p < 0.05).

Discussion: SFT, Serum IGF1, CSF aSyn and DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further investigation as possible motor progression biomarkers.
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http://dx.doi.org/10.1016/j.jns.2018.01.025DOI Listing
April 2018

Measurements of AMPs in stratum corneum of atopic dermatitis and healthy skin-tape stripping technique.

Sci Rep 2018 01 26;8(1):1666. Epub 2018 Jan 26.

Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark.

Decreased levels of antimicrobial peptides (AMPs) in atopic dermatitis (AD) have previously been reported and have been linked to the increased susceptibility to skin infections found in AD patients. This study intents to identify AMPs: hBD-2, hBD-3, RNase7, psoriasin and LL-37 in AD patients and healthy controls, and determine concentrations in consecutive depths of the outer most skin layers. Tape stripping was used on lesional and non-lesional skin. From each skin site, 35 consecutive tape strips were collected and pooled in groups of 5. Commercially available ELISA kits were used to determine AMP concentration in stratum corneum samples. hBD-2, hBD-3, RNase7 and psoriasin were identified in stratum corneum samples. hBD-3-level was markedly higher in AD non-lesional skin compared to healthy controls, and a similar trend was observed for RNase7. Most AMPs were distributed evenly through 35 tape strips, implying a homogeneous distribution of antimicrobial defense in the outer most skin layers. The findings indicate that AD patients may not suffer from a general baseline deficiency in AMPs, and that the innate immune defense is present throughout the stratum corneum, both insights of importance for understanding the role of AMPs in AD.
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http://dx.doi.org/10.1038/s41598-018-20204-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786105PMC
January 2018

Determination of the Optimal Chromosomal Location(s) for a DNA Element in Escherichia coli Using a Novel Transposon-mediated Approach.

J Vis Exp 2017 09 11(127). Epub 2017 Sep 11.

Department of Biology, Section for Functional Genomics and Center for Bacterial Stress Response and Persistence (BASP), University of Copenhagen;

The optimal chromosomal position(s) of a given DNA element was/were determined by transposon-mediated random insertion followed by fitness selection. In bacteria, the impact of the genetic context on the function of a genetic element can be difficult to assess. Several mechanisms, including topological effects, transcriptional interference from neighboring genes, and/or replication-associated gene dosage, may affect the function of a given genetic element. Here, we describe a method that permits the random integration of a DNA element into the chromosome of Escherichia coli and select the most favorable locations using a simple growth competition experiment. The method takes advantage of a well-described transposon-based system of random insertion, coupled with a selection of the fittest clone(s) by growth advantage, a procedure that is easily adjustable to experimental needs. The nature of the fittest clone(s) can be determined by whole-genome sequencing on a complex multi-clonal population or by easy gene walking for the rapid identification of selected clones. Here, the non-coding DNA region DARS2, which controls the initiation of chromosome replication in E. coli, was used as an example. The function of DARS2 is known to be affected by replication-associated gene dosage; the closer DARS2 gets to the origin of DNA replication, the more active it becomes. DARS2 was randomly inserted into the chromosome of a DARS2-deleted strain. The resultant clones containing individual insertions were pooled and competed against one another for hundreds of generations. Finally, the fittest clones were characterized and found to contain DARS2 inserted in close proximity to the original DARS2 location.
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http://dx.doi.org/10.3791/55946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752208PMC
September 2017

Genetic Virulence Profile of Enteroaggregative Strains Isolated from Danish Children with Either Acute or Persistent Diarrhea.

Front Cell Infect Microbiol 2017 30;7:230. Epub 2017 May 30.

Department of Bacteria, Parasites and Fungi, Statens Serum InstitutCopenhagen, Denmark.

Enteroaggregative (EAEC) is frequently found in diarrheal stools worldwide. It has been associated with persistent diarrhea, weight loss, and failure to thrive in children living in developing countries. A number of important EAEC virulence genes are identified; however, their roles in acute and persistent diarrhea have not been previously investigated. The aim of this study was to identify specific EAEC virulence genes associated with duration and type of diarrhea in Danish children. We aimed to improve the current diagnostics of EAEC and enable targeting of strains with an expected severe disease course. Questionnaires answered by parents provided information regarding duration of diarrhea and presence of blood or mucus. A total of 295 EAEC strains were collected from children with acute (≤7 days) and persistent diarrhea (≥14 days) and were compared by using multiplex PCR targeting the genes , and . Furthermore, the distribution of EAEC genes in strains collected from cases of bloody, mucoid, and watery diarrhea was investigated. The classification and regression tree analysis (CART) was applied to investigate the relationship between EAEC virulence genes and diarrheal duration and type. Persistent diarrhea was associated with strains lacking the gene ( = 0.002) and with the combination of the genes , and absence of the gene ( = 0.05). Prolonged diarrhea was associated with the combination of the genes and ( = 0.03). Non-mucoid diarrhea was associated with strains lacking the gene ( = 0.004). Acute diarrhea was associated with the genes , and by individual odds ratios. Resistance toward gentamicin and ciprofloxacin was observed in 7.5 and 3% of strains, respectively. Multi-drug resistance was observed in 38% of strains. Genetic host factors have been associated with an increased risk of EAEC-associated disease. Therefore, we investigated a panel of risk factors in two groups of children-EAEC-positive and EAEC-negative-to identify additional factors predisposing to disease. The duration of breastfeeding was positively correlated with the likelihood of belonging to the EAEC-negative group of children.
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http://dx.doi.org/10.3389/fcimb.2017.00230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447714PMC
January 2018

Enteroaggregative Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1.

mBio 2017 06 6;8(3). Epub 2017 Jun 6.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA

Enteroaggregative (EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen. EAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs-the principal adhesins of EAEC-in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.
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http://dx.doi.org/10.1128/mBio.00717-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461410PMC
June 2017

Turn Up the Heat-Food and Clinical Isolates Feature Two Transferrable Loci of Heat Resistance.

Front Microbiol 2017 7;8:579. Epub 2017 Apr 7.

Department of Microbiology and Infection Control, Statens Serum InstitutCopenhagen, Denmark.

Heat treatment is a widely used process to reduce bacterial loads in the food industry or to decontaminate surfaces, e.g., in hospital settings. However, there are situations where lower temperatures must be employed, for instance in case of food production such as raw milk cheese or for decontamination of medical devices such as thermo-labile flexible endoscopes. A recently identified locus of heat resistance (LHR) has been shown to be present in and confer heat resistance to a variety of , including isolates from food production settings and clinical ESBL-producing isolates. Here, we describe the presence of two distinct LHR variants within a particularly heat resistant raw milk cheese isolate. We demonstrate for the first time in this species the presence of one of these LHRs on a plasmid, designated pFAM21805, also encoding type 3 fimbriae and three bacteriocins and corresponding self-immunity proteins. The plasmid was highly transferable to other strains, including Shiga-toxin-producing strains, and conferred LHR-dependent heat resistance as well as type 3 fimbriae-dependent biofilm formation capabilities. Selection for and acquisition of this "survival" plasmid by pathogenic organisms, e.g., in food production environments, may pose great concern and emphasizes the need to screen for the presence of LHR genes in isolates.
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http://dx.doi.org/10.3389/fmicb.2017.00579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383660PMC
April 2017

Cranberry Juice and Combinations of Its Organic Acids Are Effective against Experimental Urinary Tract Infection.

Front Microbiol 2017 4;8:542. Epub 2017 Apr 4.

Department of Bacteria, Parasites and Fungi, Statens Serum InstitutCopenhagen, Denmark.

The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder ( < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced ( < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice ( < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together ( < 0.001), and so did the combination of malic plus citric acid ( < 0.01) and malic plus quinic acid ( < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents.
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http://dx.doi.org/10.3389/fmicb.2017.00542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378705PMC
April 2017
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