Publications by authors named "Jacques Schrenzel"

317 Publications

Unexpectedly High False-Positive Rates for Using a Meningoencephalitis Syndromic PCR Panel in Two Tertiary Centers.

Front Cell Infect Microbiol 2021 8;11:639658. Epub 2021 Mar 8.

Laboratory of Bacteriology, Division of Laboratory Medicine and Division of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland.

False-positive results in the diagnostic of meningitis and encephalitis pose important challenges. This study aimed to determine false-positive rates for in cerebrospinal fluids evaluated by the BioFire FilmArray Meningitis/Encephalitis Panel. We conducted a retrospective study of all -positive FilmArray. Meningitis/Encephalitis Panel results from June 2016 to October 2019 in two Swiss university hospitals. Cases were classified as true positive, likely true-positive, and likely false-positive results according to cerebrospinal fluid culture, -specific quantitative real-time PCR (qPCR), and Gram staining, as well as culture of other materials. We performed 3,082 panels corresponding to 2,895 patients: 0.6% of the samples (18/3,082) were positive for . Culture and -specific qPCR were performed on 17/18 (94.4%) and 3/18 (16.7%) cerebrospinal fluid samples, respectively; qPCR was negative in all cases. Among 17 samples sent for culture, 10 concerned patients were not treated with antibiotics prior to lumbar puncture. Only 1/17 revealed growth of and was classified as a true positive. We further classified 3/18 (16.7%) cases with the identification of Gram-negative rods in the cerebrospinal fluid or positive blood cultures for as likely true-positive and 14/18 (77.8%) cases as likely false-positive. Diagnostic results should always be interpreted together with the clinical presentation, cerebrospinal fluid analysis, and other available microbiological results. All -positive results should be viewed with special caution and a specific qPCR should be systematically considered.
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http://dx.doi.org/10.3389/fcimb.2021.639658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982903PMC
March 2021

Oral Dysbiosis and Inflammation in Parkinson's Disease.

J Parkinsons Dis 2021 Feb 25. Epub 2021 Feb 25.

Faculty of Medicine, University of Geneva, CMU, Geneva, Switzerland.

Background: Oral microbiota has largely escaped attention in Parkinson's disease (PD), despite its pivotal role in maintaining oral and systemic health.

Objective: The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD.

Methods: Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities.

Results: PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2-2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant.

Conclusion: Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.
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http://dx.doi.org/10.3233/JPD-202459DOI Listing
February 2021

NGS-Based Typing and Outbreak Analysis in Clinical Microbiology Laboratories: Lessons Learned From a Swiss-Wide Proficiency Test.

Front Microbiol 2020 24;11:591093. Epub 2020 Nov 24.

SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.

Whole genome sequencing (WGS) enables high resolution typing of bacteria up to the single nucleotide polymorphism (SNP) level. WGS is used in clinical microbiology laboratories for infection control, molecular surveillance and outbreak analyses. Given the large palette of WGS reagents and bioinformatics tools, the Swiss clinical bacteriology community decided to conduct a ring trial (RT) to foster harmonization of NGS-based bacterial typing. The RT aimed at assessing methicillin-susceptible strain relatedness from WGS and epidemiological data. The RT was designed to disentangle the variability arising from differences in sample preparation, SNP calling and phylogenetic methods. Nine laboratories participated. The resulting phylogenetic tree and cluster identification were highly reproducible across the laboratories. Cluster interpretation was, however, more laboratory dependent, suggesting that an increased sharing of expertise across laboratories would contribute to further harmonization of practices. More detailed bioinformatic analyses unveiled that while similar clusters were found across laboratories, these were actually based on different sets of SNPs, differentially retained after sample preparation and SNP calling procedures. Despite this, the observed number of SNP differences between pairs of strains, an important criterion to determine strain relatedness given epidemiological information, was similar across pipelines for closely related strains when restricting SNP calls to a common core genome defined by cgMLST schema. The lessons learned from this pilot study will serve the implementation of larger-scale RT, as a mean to have regular external quality assessments for laboratories performing WGS analyses in a clinical setting.
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http://dx.doi.org/10.3389/fmicb.2020.591093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793906PMC
November 2020

Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae.

J Glob Antimicrob Resist 2021 Mar 26;24:183-189. Epub 2020 Dec 26.

Service of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland; Genomic Research Laboratory, Service of Infectious Diseases, Geneva University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address:

Objectives: Carbapenem resistance in Klebsiella pneumoniae is a major clinical challenge. Aminoglycosides remain an important asset in the current therapeutic arsenal to treat these infections. We examined aminoglycoside resistance phenotypes and genomics in a collection of 100 invasive KPC-producing K. pneumoniae isolates sequentially collected in a Brazilian tertiary hospital between 2014 and 2016.

Methods: Aminoglycoside susceptibility testing was performed. We used a combined long-read (MinION) and short-read (Illumina) whole-genome sequencing strategy to provide a genomic picture of aminoglycoside resistance genes, with particular emphasis on 16S rRNA methyltransferases and related plasmids.

Results: 68% of the strains were resistant to gentamicin and 42% to amikacin, with 35% resistant to both of these commonly used aminoglycosides. We identified the 16S rRNA methyltransferase gene rmtB in 30% of these isolates: 97% (29/30) belonged to sequence type 258 (ST258) and a single isolate to the emergent ST16 clone. In ST258 and ST16 the rmtB gene was located on large IncC plasmids of 177 kb and 174 kb, respectively, highly similar to a plasmid previously identified in Proteus mirabilis in the same hospital. Moreover, 99% of the isolates remained susceptible to the veterinary-approved drug apramycin, currently under clinical development for human medicine.

Conclusion: Such findings in geographically and temporally related isolates suggest a combination of vertical clonal spread as well as horizontal interspecies and intraspecies plasmid transfer. This broad rmtB dissemination in an endemic setting for KPC-producing clones is worrisome since it provides resistance to most clinically available aminoglycosides, including the novel aminoglycoside-modifying enzyme-resistant plazomicin.
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http://dx.doi.org/10.1016/j.jgar.2020.12.006DOI Listing
March 2021

Mini Review: Clinical Routine Microbiology in the Era of Automation and Digital Health.

Front Cell Infect Microbiol 2020 30;10:582028. Epub 2020 Nov 30.

Genomic Research Laboratory, Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.

Clinical microbiology laboratories are the first line to combat and handle infectious diseases and antibiotic resistance, including newly emerging ones. Although most clinical laboratories still rely on conventional methods, a cascade of technological changes, driven by digital imaging and high-throughput sequencing, will revolutionize the management of clinical diagnostics for direct detection of bacteria and swift antimicrobial susceptibility testing. Importantly, such technological advancements occur in the golden age of machine learning where computers are no longer acting passively in data mining, but once trained, can also help physicians in making decisions for diagnostics and optimal treatment administration. The further potential of physically integrating new technologies in an automation chain, combined to machine-learning-based software for data analyses, is seducing and would indeed lead to a faster management in infectious diseases. However, if, from one side, technological advancement would achieve a better performance than conventional methods, on the other side, this evolution challenges clinicians in terms of data interpretation and impacts the entire hospital personnel organization and management. In this mini review, we discuss such technological achievements offering practical examples of their operability but also their limitations and potential issues that their implementation could rise in clinical microbiology laboratories.
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http://dx.doi.org/10.3389/fcimb.2020.582028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734209PMC
November 2020

Impact of Total Laboratory Automation on Turnaround Times for Urine Cultures and Screening Specimens for MRSA, ESBL, and VRE Carriage: Retrospective Comparison With Manual Workflow.

Front Cell Infect Microbiol 2020 28;10:552122. Epub 2020 Oct 28.

Bacteriology Laboratory, Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals, Geneva, Switzerland.

Using computerized time-stamps, we compared the turnaround-times (TAT) for urine samples and screening ESwabs of MRSA, VRE, and ESBL carriage in the bacteriology laboratory of Geneva University Hospitals between January and December 2017 (period preceding the implementation of the WASPLab) with the same specimen types analyzed between January and December 2019 (period after the implementation of the automation). During both 1-year periods, a total of 98'380 specimens were analyzed (48'158 in 2017 vs. 50'222 in 2019). On the WASPLab, all culture plates were imaged at defined intervals each day of incubation, but the processing of the cultures (i.e., pathogen identification and antimicrobial susceptibility testing) was only performed during day shift hours (~8:00 A.M. to 4:30 P.M.). The median TAT for negative reports decreased by almost half for urine samples from 52.1 (2017) to 28.3 h (2019) ( < 0.001), and for MRSA screening specimens from 50.7 to 26.3 h ( < 0.001). The difference in median TAT for negative reports was less pronounced for screening of ESBL (50.2 vs. 43.0 h) ( < 0.001) and VRE (50.6 vs. 45.7 h) ( < 0.001). Despite a trend toward shorter result delivery for positive samples, there was no significant change in the median TAT. These results suggest that TAT for negative samples immediately benefit from automation, whereas TAT for positive samples also depend on the laboratory hours of operation and daily human resource management.
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http://dx.doi.org/10.3389/fcimb.2020.552122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664309PMC
October 2020

Mapping of aetiologies of gastroenteritis: a systematic review and meta-analysis of pathogens identified using a multiplex screening array.

Scand J Gastroenterol 2020 Dec 4;55(12):1405-1410. Epub 2020 Nov 4.

Laboratory of Bacteriology, University Hospitals of Geneva, Genève, Switzerland.

Objective: Emergence of molecular methods to screen stools could provide a more complete picture of pathogens causing gastroenteritis, allowing to adequately treat patients whenever required but, so far, no aggregate data have been released. Our objective was to report pathogens identified in patients suffering from gastroenteritis using a multiplex molecular array.

Design: Medline and Embase were searched for original publications reporting pathogens identified with FilmArray GI panel in patients suffering from gastroenteritis. Proportions of pathogens were extracted and pooled using a model with random effects.

Results: Fourteen studies (17,815 patients) were included in the analysis. Among the 7,071 patients (39.7%) with positive FilmArray, identified pathogens were (27.5%), (19.3%), (15.1%), (15%), (11.8%), (8.1%), (7.3%), (7.3%), (7.1%), (5.2%), (4.9%), (4%), (3.8%), (3.8%), (2.8%), (1.7%), O157 (1.1%), (1.1%), (0.7%), (0.5%), (0.3%) and (0.3%). When considering only studies with control group (microbiological examination of the stools performed by other methods), FilmArray identified at least one pathogen in 48.2% of patients versus 16.7% when using comparative diagnostic methods.

Conclusions: FilmArray GI panel was positive in 39.7% of patients suffering from gastroenteritis. This proportion has to be mitigated by the carriage rates of identified organisms. Ultimately, restricted ordering of molecular panels to those patients who might benefit from specific treatment could provide medical value by swift identification of the pathogen and more targeted therapy.
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http://dx.doi.org/10.1080/00365521.2020.1839128DOI Listing
December 2020

Phylogeographical Analysis Reveals the Historic Origin, Emergence, and Evolutionary Dynamics of Methicillin-Resistant ST228.

Front Microbiol 2020 26;11:2063. Epub 2020 Aug 26.

Service of Hospital Preventive Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: Methicillin-resistant (MRSA) is a common healthcare-associated pathogen that remains a major public health concern. Sequence type 228 (ST228) was first described in Germany and spread to become a successful MRSA clone in several European countries. In 2000, ST228 emerged in Lausanne and has subsequently caused several large outbreaks. Here, we describe the evolutionary history of this clone and identify the genetic changes underlying its expansion in Switzerland.

Materials And Methods: We aimed to understand the phylogeographic and demographic dynamics of MRSA ST228/ST111 by sequencing 530 representative isolates of this clone that were collected from 14 European countries between 1997 and 2012.

Results: The phylogenetic analysis revealed distinct lineages of ST228 isolates associated with specific geographic origins. In contrast, isolates of ST111, which is a single locus variant of ST228 sharing the same type t041, formed a monophyletic cluster associated with multiple countries. The evidence points to a German origin of the sampled population, with the basal German lineage being characterized by type t001. The highly successful Swiss ST228 lineage diverged from this progenitor clone through the loss of the aminoglycoside-streptothricin resistance gene cluster and the gain of mupirocin resistance. This lineage was introduced first in Geneva and was subsequently introduced into Lausanne.

Conclusion: Our results reveal the radiation of distinct lineages of MRSA ST228 from a German progenitor, as the clone spread into different European countries. In Switzerland, ST228 was introduced first in Geneva and was subsequently introduced into Lausanne.
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http://dx.doi.org/10.3389/fmicb.2020.02063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479193PMC
August 2020

Discordant diagnostic assay and treatment practice: a cross-sectional study in a tertiary care hospital, Geneva, Switzerland.

BMJ Open 2020 09 13;10(9):e036342. Epub 2020 Sep 13.

Division of Infectious Diseases, Geneva University Hospitals, Geneve, Switzerland.

Objectives: To determine the proportion of patients who received a treatment for infection (CDI) among those presenting a discordant diagnostic assay and to identify patient characteristics associated with the decision to treat CDI.

Design: Cross-sectional study.

Setting: Monocentric study in a tertiary care hospital, Geneva, Switzerland.

Participants: Among 4562 adult patients tested for between March 2017 and March 2019, 208 patients with discordant tests' results (positive nucleic acid amplification test (NAAT+)/negative enzyme immunoassay (EIA-)) were included.

Main Outcome Measures: Treatment for CDI.

Results: CDI treatment was administered in 147 (71%) cases. In multivariate analysis, an abdominal CT scan with signs of colitis (OR 14.7; 95% CI 1.96 to 110.8) was the only factor associated with CDI treatment.

Conclusions: The proportion of NAAT+/EIA- patients who received treatment questions the contribution of the EIA for the detection of toxin A/B after NAAT to limit overtreatment. Additional studies are needed to investigate if other factors are associated with the decision to treat.
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http://dx.doi.org/10.1136/bmjopen-2019-036342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488797PMC
September 2020

Messages from the Fourth International Conference on Clinical Metagenomics.

Microbes Infect 2020 Nov - Dec;22(10):635-641. Epub 2020 Aug 20.

AP-HP, Hôpital Bichat - Claude Bernard, Laboratoire de Bactériologie, INSERM, IAME, UMR 1137, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, 46 Rue Henri-Huchard, Paris, 75018, France.

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http://dx.doi.org/10.1016/j.micinf.2020.07.007DOI Listing
August 2020

The GLP-1R agonist liraglutide limits hepatic lipotoxicity and inflammatory response in mice fed a methionine-choline deficient diet.

Transl Res 2021 01 22;227:75-88. Epub 2020 Jul 22.

Service of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Internal Medicine, Geneva University Hospitals/University of Geneva, Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorder related to type 2 diabetes (T2D). The disease can evolve toward nonalcoholic steatohepatitis (NASH), a state of hepatic inflammation and fibrosis. There is presently no drug that effectively improves and/or prevents NAFLD/NASH/fibrosis. GLP-1 receptor agonists (GLP-1Ra) are effective in treating T2D. As with the endogenous gut incretins, GLP-1Ra potentiate glucose-induced insulin secretion. In addition, GLP-1Ra limit food intake and weight gain, additional beneficial properties in the context of obesity/insulin-resistance. Nevertheless, these pleiotropic effects of GLP-1Ra complicate the elucidation of their direct action on the liver. In the present study, we used the classical methionine-choline deficient (MCD) dietary model to investigate the potential direct hepatic actions of the GLP-1Ra liraglutide. A 4-week infusion of liraglutide (570 µg/kg/day) did not impact body weight, fat accretion or glycemic control in MCD-diet fed mice, confirming the suitability of this model for avoiding confounding factors. Liraglutide treatment did not prevent lipid deposition in the liver of MCD-fed mice but limited the accumulation of C16 and C24-ceramide/sphingomyelin species. In addition, liraglutide treatment alleviated hepatic inflammation (in particular accumulation of M1 pro-inflammatory macrophages) and initiation of fibrosis. Liraglutide also influenced the composition of gut microbiota induced by the MCD-diet. This included recovery of a normal Bacteroides proportion and, among the Erysipelotrichaceae family, a shift between Allobaculum and Turicibacter genera. In conclusion, liraglutide prevents accumulation of C16 and C24-ceramides/sphingomyelins species, inflammation and initiation of fibrosis in MCD-diet-fed mice liver, suggesting beneficial hepatic actions independent of weight loss and global hepatic steatosis.
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http://dx.doi.org/10.1016/j.trsl.2020.07.008DOI Listing
January 2021

Population structure, genetic diversity and pathotypes of Streptococcus suis isolated during the last 13 years from diseased pigs in Switzerland.

Vet Res 2020 Jul 8;51(1):85. Epub 2020 Jul 8.

Department of Veterinary Bacteriology, Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Streptococcus (S.) suis is a globally important swine pathogen, which comprises certain zoonotic serotypes. In this study, a detailed characterization of 88 porcine S. suis isolates was performed by analyzing capsular (cps) types, multilocus sequence typing (MLST) and investigation of the minimum core genome (MCG). In order to focus on the virulence potential of presumable invasive disease-associated S. suis isolates, virulence-associated gene profiles were assessed followed by screening a chosen subset of S. suis strains with a molecular pathotyping tool. Results showed a high genetic variability within this strain collection. In total, seventeen cps types were identified with a predominance of cps type 9 (15.9%) and 6 (14.8%). MLST revealed 48 sequence types (STs) including 41 novel ones. The population structure of S. suis was heterogenous and isolates belonged to eight different clonal complexes (CCs) including CC28 (9.1%), CC1109 (8%), CC13/149 (6.8%), CC1237 (5.7%), CC1 (3.4%), CC17 (3.4%), CC87 (2.3%), and CC1112 (1.1%), whereas a significant portion of isolates (60.2%) could not be assigned to any described CCs. Virulence-associated markers, namely extracellular protein factor (epf), muramidase-released protein (mrp), and suilysin (sly), showed a link with STs rather than with cps types. With this study an expanded knowledge about the population structure and the genetic diversity of S. suis could be achieved, which helps to contribute to an optimal public health surveillance system by promoting a focus on strains with an increased virulence and zoonotic potential.
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http://dx.doi.org/10.1186/s13567-020-00813-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346511PMC
July 2020

Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.

Microorganisms 2020 Jun 23;8(6). Epub 2020 Jun 23.

Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva, Switzerland.

The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.
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http://dx.doi.org/10.3390/microorganisms8060941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357103PMC
June 2020

SPHN/PHRT: Forming a Swiss-Wide Infrastructure for Data-Driven Sepsis Research.

Stud Health Technol Inform 2020 Jun;270:1163-1167

Department of Biosystems Science and Engineering, ETH Zurich, Basel.

Sepsis is a highly heterogenous syndrome with variable causes and outcomes. As part of the SPHN/PHRT funding program, we aim to build a highly interoperable, interconnected network for data collection, exchange and analysis of patients on intensive care units in order to predict sepsis onset and mortality earlier. All five University Hospitals, Universities, the Swiss Institute of Bioinformatics and ETH Zurich are involved in this multi-disciplinary project. With two prospective clinical observational studies, we test our infrastructure setup and improve the framework gradually and generate relevant data for research.
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http://dx.doi.org/10.3233/SHTI200346DOI Listing
June 2020

Strain coverage of Bexsero vaccine assessed by whole-genome sequencing over a cohort of invasive meningococci of serogroups B and W isolated in Switzerland.

Vaccine 2020 07 16;38(33):5324-5331. Epub 2020 Jun 16.

Genomic Research Laboratory, Division of Infectious Diseases, University Hospitals and University of Geneva, Geneva, Switzerland; Swiss National Reference Center for Meningococci (www.meningo.ch), Bacteriology Laboratory, Geneva University Hospitals, Geneva, Switzerland. Electronic address:

Invasive meningococcal disease (IMD), caused by Neisseria meningitidis (Nm) strains, is a life-threatening but vaccine-preventable condition. Bexsero is a four-component vaccine that offers broad protection against Nm of serogroup B (NmB), particularly common in Europe. In Switzerland, Bexsero has not yet been licensed and no information is available concerning the predicted vaccine coverage on isolates of circulating Nm. We performed genotyping of Bexsero antigen loci by whole-genome sequencing (WGS) on 104 NmB collected in Switzerland in the 2010-2015 period. We searched for antigen variants previously defined as predictors of strain coverage and estimated that 50% of IMD NmB strains were potentially covered by the vaccine. Clonal complexes (cc) 32, 41/44 and 269, considered the best covered lineages, were further sub-typed according to Bexsero Antigen Sequence Type (BAST) scheme. We also genotyped by WGS 40 Nm of serogroup W (NmW) collected in the country between 2010 and 2016. NmW cc22 isolates appeared to be covered by the vaccine, which was not the case for cc11 isolates, whose incidence has recently increased in Switzerland and all over Europe. Our work underlines the benefit of using WGS for surveillance of vaccine antigen variant distribution in local Nm population and taking proper measures to prevent the spread of NmB.
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http://dx.doi.org/10.1016/j.vaccine.2020.05.071DOI Listing
July 2020

[Microbiota specificities among the elderly Summary of the 5th symposium « Feeding the Microbiota »].

Rev Med Suisse 2020 Jun;16(698):1266-1269

Service des maladies infectieuses, HUG, 1211 Genève 14.

The microbiota is a subject of particular interest and research. It is defined as all microorganisms present in tissues and on body surfaces. It sits at the interface with many systems, including the immune system, plays a role in the metabolism, immunity, or inflammation and is thought to be associated with some pathological mechanisms. Its composition and metabolic activity are influenced by diverse factors such as aging. This article summarizes the 5th symposium « Feeding the Microbiota » (Geneva University Hospitals, February 6, 2020), focused on microbiota and aging.
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June 2020

Influenza-associated aspergillosis in critically-ill patients-a retrospective bicentric cohort study.

Eur J Clin Microbiol Infect Dis 2020 Oct 3;39(10):1915-1923. Epub 2020 Jun 3.

Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, CH - 9007, St. Gallen, Switzerland.

Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.
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http://dx.doi.org/10.1007/s10096-020-03923-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266735PMC
October 2020

Septic shock caused by Capnocytophaga canis after a cat scratch.

Eur J Clin Microbiol Infect Dis 2020 Oct 24;39(10):1993-1995. Epub 2020 May 24.

Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.

Capnocytophaga canis is an uncommon cause of septic shock. Only three cases have been previously reported in the literature. In this article, we describe the case of a 70-year-old male admitted to the intensive care unit for septic shock of unknown origin. On day 2, one anaerobic bottle out of the two sets taken at admission turned positive with Gram-negative bacilli. The pathogen was identified by 16S rRNA gene as C. canis. The strain was characterized and compared with other clinical isolates of Capnocytophaga spp.
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http://dx.doi.org/10.1007/s10096-020-03922-8DOI Listing
October 2020

Performances and usefulness of Xpert MTB/RIF assay in low-incidence settings: not that bad?

Eur J Clin Microbiol Infect Dis 2020 Sep 18;39(9):1645-1649. Epub 2020 Apr 18.

Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, CH 1211, Geneva, Switzerland.

Xpert MTB/RIF assay, a real-time PCR assay designed to detect Mycobacterium tuberculosis, has proven sensitive and specific when performed on respiratory samples in a high prevalence setting. However, it was suggested as less accurate in a low-incidence environment. We evaluated the accuracy of the Xpert for the diagnosis of tuberculosis (TB) on pulmonary and extrapulmonary samples in Geneva (Switzerland), where the prevalence of active TB is very low. From March 2009 to February 2013, the Xpert was performed on clinical samples. All specimens were also processed using auramine, AFB staining, and mycobacterial culture with both solid and liquid media. The accuracy of both microscopy and Xpert was determined retrospectively using cultures as the reference method. A total of 732 clinical specimens were processed with the Xpert. The Xpert had a high specificity (97.5%; 95% confidence interval (CI), 95.8-98.5%) and revealed much more sensitive (82.7%; 95% CI, 74.1-89.0%) than microscopy (55.5%; 95% CI, 45.7-64.8%) for the diagnosis of TB, with a high negative predictive value (96.8%; 95% CI, 95.0-98.0%). The advantage of PCR over microscopy was even more pronounced for extrapulmonary specimens (sensitivity of 70% (95% CI, 50.4-84.6%) compared with 23.3% (95% CI, 10.6-42.7%)). Despite the low prevalence of TB in Switzerland, results performance for respiratory samples was similar to that reported in high prevalence countries. The high negative predictive value is clinically helpful in our setting, where pulmonary TB needs to be reasonably ruled out. When considering extrapulmonary samples, microscopy performed poorly compared with Xpert. This study shows that the Xpert remains accurate and useful in a low-incidence setting.
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http://dx.doi.org/10.1007/s10096-020-03887-8DOI Listing
September 2020

Implementation of the WASPLab™ and first year achievements within a university hospital.

Eur J Clin Microbiol Infect Dis 2020 Aug 5;39(8):1527-1534. Epub 2020 Apr 5.

Bacteriology Laboratory, Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals, Geneva, Switzerland.

In essence, automation can be driven by several of the following incentives: increased processing capacity of the laboratory, better costs control through processes standardization, optimized traceability, or improved workflows to reduce turnaround times (TAT). This project aims at presenting an overview of the project management and change management with a focus on the major challenges addressed by lab staff and laboratory leadership during the different phases of the implementation of the WASPLab™ in a routine clinical bacteriology laboratory. This paper reports our experience and reviews changes in the bacteriology laboratory at Geneva University Hospitals when shifting to the WASPLab™. Practically, the whole automation process was segmented into different packages (specimen type-based segmentation) allowing sequential validation, staff training, and routine implementation. Such process allowed reaching 90% of the identified "automatable" samples within 1 year, including personal training, documentation for accreditation supported by publications, without interrupting routine operations. In addition, we implemented a validated automated solution for antimicrobial disk diffusion susceptibility testing. Structured supervision and accurate monitoring of all the activities related to the automation project including key partners such as IT support, technical committee, and after-sales service guaranteed a swift and timely achievement of the project allowing the improvement of the workflow in routine bacteriology within 1 year.
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http://dx.doi.org/10.1007/s10096-020-03872-1DOI Listing
August 2020

Changes in Microbiota Profiles After Prolonged Frozen Storage of Stool Suspensions.

Front Cell Infect Microbiol 2020 28;10:77. Epub 2020 Feb 28.

Genomic Research Laboratory, Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.

Fecal microbiota transplantation (FMT) is recommended as safe and effective treatment for recurrent infections. Freezing the FMT preparation simplifies the process, allowing a single stool sample to be used for multiple receivers and over an extended period of time. We aimed to assess the effect of long-term frozen storage on bacterial taxonomic profiles of a stool suspension prepared for FMT. DNA was extracted from a stool suspension before freezing and sequentially during the 18-month storage period at -80°C. Two different protocols were used for DNA extraction. The first relied on a classical mechanical and chemical cell disruption to extract both intra- and extracellular DNA; the second included specific pre-treatments aimed at removing free DNA and DNA from human and damaged bacterial cells. Taxonomic profiling of bacterial communities was performed by sequencing of V3-V4 16S rRNA gene amplicons. Microbiota profiles obtained by whole DNA extraction procedure remained relatively stable during frozen storage. When DNA extraction procedure included specific pre-treatments, microbiota similarity between fresh and frozen samples progressively decreased with longer frozen storage times; notably, the abundance of Bacteroidetes decreased in a storage duration-dependent manner. The abundance of Firmicutes, the main butyrate producers in the colon, were not much affected by frozen storage for up to 1 year. Our data show that metataxonomic analysis of frozen stool suspensions subjected to specific pre-treatments prior to DNA extractions might provide an interesting indication of bacterial resistance to stress conditions and thus of chances of survival in FMT recipients.
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http://dx.doi.org/10.3389/fcimb.2020.00077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058979PMC
March 2021

Second Periprosthetic Joint Infection Caused by : How Genomic Sequencing Can Help Defining the Best Therapeutic Strategy.

Front Med (Lausanne) 2020 21;7:53. Epub 2020 Feb 21.

Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.

Primary and revision arthroplasties are increasing worldwide, as are periprosthetic joint infections (PJI). The management of PJI requires surgery, the strategy of which is dictated by the acute or chronic nature of the infection, with an exchange of the implant in the event of a chronic PJI or in the case of recurrence with the same pathogen. We report the case of a 63-year-old man with two episodes of subsp. PJI within 9 months. Based on clinical suspicion of an haematogenous PJI, the patient was treated by DAIR (debridement, antibiotics, implant retention), while genomic sequencing revealed two different strains, confirming our hypothesis that no additional surgery was needed. Hence, we report a case where genomic analysis was decisive for the decision of the best therapeutic strategy.
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http://dx.doi.org/10.3389/fmed.2020.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046550PMC
February 2020

First case of Streptococcus suis infection in Switzerland: An emerging public health problem?

Travel Med Infect Dis 2020 Jul - Aug;36:101590. Epub 2020 Mar 5.

Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Geneva, Switzerland; Bacteriology Laboratory, Division of Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland; Genomic Research Laboratory, Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland.

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http://dx.doi.org/10.1016/j.tmaid.2020.101590DOI Listing
March 2020

Rapid high resolution melting assay to differentiate Streptococcus suis serotypes 2, 1/2, 1, and 14.

Microbiologyopen 2020 04 22;9(4):e995. Epub 2020 Jan 22.

Department of Veterinary Bacteriology, Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

This rapid high resolution melting (HRM) assay allows distinguishing between Streptococcus suis serotype pairs 2 and 1/2 as well as 1 and 14, respectively, based on a single-nucleotide polymorphism within capsular polysaccharide synthesis gene cluster K. This assay is easy to implement and identifies potential zoonotic serotypes.
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http://dx.doi.org/10.1002/mbo3.995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142366PMC
April 2020

Rapid identification by MALDI-TOF/MS and antimicrobial disk diffusion susceptibility testing for positive blood cultures after a short incubation on the WASPLab.

Eur J Clin Microbiol Infect Dis 2020 Jun 21;39(6):1063-1070. Epub 2020 Jan 21.

Department of Diagnostics, Bacteriology Laboratory, Division of Laboratory Medicine, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1205, Geneva, Switzerland.

The objectives of this study were to define the shortest incubation times on the WASPLab for reliable MALDI-TOF/MS-based species identification and for the preparation of a 0.5 McFarland suspension for antimicrobial disk diffusion susceptibility testing using short subcultures growing on solid culture media inoculated by positive blood cultures spiked with a wide range of pathogens associated with bloodstream infections. The 520 clinical strains (20 × 26 different species) included in this study were obtained from a collection of non-consecutive and non-duplicate pathogens identified at Geneva University Hospitals. After 4 h of incubation on the WASPLab, microorganisms' growth allowed accurate identification of 73% (380/520) (95% CI, 69.1-76.7%) of the strains included in this study. The identification rate increased to 85% (440/520) (95% CI, 81.3-87.5%) after 6-h incubation. When excluding Corynebacterium and Candida spp., the microbial growth was sufficient to permit accurate identification of all tested species (100%, 460/460) (95% CI, 99.2-100%) after 8-h incubation. With the exception of Burkholderia cepacia and Haemophilus influenzae, AST by disk diffusion could be performed for Enterobacterales and non-fermenting Gram-negative bacilli after only 4 h of growth in the WASPLab. The preparation of a 0.5 McFarland suspension for Gram-positive bacteria required incubation times ranging between 3 and 8 h according to the bacterial species. Only Corynebacterium spp. required incubation times as long as 16 h. The WASPLab enables rapid pathogen identification as well as swift comprehensive AST from positive blood cultures that can be implemented without additional costs nor hands-on time by defining optimal time points for image acquisition.
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http://dx.doi.org/10.1007/s10096-020-03817-8DOI Listing
June 2020

Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in Staphylococcus aureus.

mSystems 2020 Jan 7;5(1). Epub 2020 Jan 7.

Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

contains a repertoire of at least 50 and possibly 500 small RNAs (sRNAs). The functions of most sRNAs are not understood, although some are known to respond to environmental changes, including the presence of antibiotics. Here, in an effort to better understand the roles of sRNAs in the context of antibiotic exposure, we took a clinical methicillin-resistant (MRSA) isolate and separately deleted eight sRNAs that were significantly upregulated in response to the last-line antibiotic linezolid as revealed by transcriptome sequencing (RNA-seq) comparisons. We also deleted an additional 10 sRNAs that were either highly expressed or previously found to respond to antibiotic exposure. There were no significant changes for any of the 18 mutants in a variety of phenotypic screens, including MIC screens, growth competition assays in the presence of linezolid, biofilm formation, and resistance to whole-blood killing. These data suggest sRNA functional redundancy, because despite their high expression levels upon antibiotic exposure, individual sRNA genes do not affect readily observable bacterial phenotypes. The sRNA transcriptional changes we measured during antibiotic exposure might also reflect sRNA "indifference," that is, a general stress response not specifically related to sRNA function. These data underscore the need for sensitive assays and new approaches to try and decipher the functions of sRNA genes in Bacterial small RNAs (sRNAs) are RNA molecules that can have important regulatory roles across gene expression networks. There is a growing understanding of the scope and potential breadth of impact of sRNAs on global gene expression patterns in , a major human pathogen. Here, transcriptome comparisons were used to examine the roles of sRNA genes with a potential role in the response of to antibiotic exposure. Although no measurable impact on key bacterial phenotypes was observed after deleting each of 18 sRNAs identified by these comparisons, this research is significant because it underscores the subtle modes of action of these sometimes abundant molecules within the bacterium.
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http://dx.doi.org/10.1128/mSystems.00665-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946794PMC
January 2020

Automated Incubation and Digital Image Analysis of Chromogenic Media Using Copan WASPLab Enables Rapid Detection of Vancomycin-Resistant Enterococcus.

Front Cell Infect Microbiol 2019 6;9:379. Epub 2019 Nov 6.

Bacteriology Laboratory, Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals, Geneva, Switzerland.

The aim of the present study was to assess whether the WASPLab automation enables faster detection of vancomycin-resistant (VRE) on chromogenic VRE-specific plates by shortening the incubation time. Ninety different VRE culture negative rectal ESwab specimens were spiked with various concentrations (ranging from 3 × 10 to 3 × 10 CFU/ml) of 10 strains (vancomycin MICs ranging from 32 to >256 mg/l), 3 VanB strains (vancomycin MICs: 4, 8, and 16 mg/l), and 2 VanB strains displaying vancomycin heteroresistance (vancomycin MICs: 64 and 96 mg/l). Besides the two strains exhibiting vancomycin heteroresistance, all the other 13 VRE strains included in this study were detected as early as 24 h on the WASPLab even if the inoculum was low (3 × 10 CFU/ml). When the vancomycin MICs were high, all strains were detected as early as at 18 h. However, 30 h was a conservative time point for finalizing the analysis of chromogenic cultures. These results suggested that the WASPLab automated incubation could allow decreasing the initial incubation time to 18 h, followed by an intermediate time at 24 h and a final incubation period of 30 h for VRE culture screening, to deliver rapid results without affecting the analytical sensitivity.
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http://dx.doi.org/10.3389/fcimb.2019.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851235PMC
July 2020

Atypical presentation of Lemierre's syndrome: case report and literature review.

BMC Infect Dis 2019 Oct 21;19(1):868. Epub 2019 Oct 21.

Service of Infectious Diseases, Department of Medicine, Geneva University Hospitals and the University of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland.

Background: The classic Lemierre's syndrome refers to a septic thrombosis of the internal jugular vein, usually caused by a Fusobacterium necrophorum infection starting in the oral cavity, and typically complicated by pulmonary emboli. However, unusual forms of the disorder have been rarely reported.

Case Presentation: We describe an unusual case of a previously healthy 58-year-old male with Lemierre's syndrome, manifesting with lumbar pain and fever. A thrombosis of the iliac veins and abscesses in the right iliac and the left psoas muscles was diagnosed by a computed tomography scan, together with a right lung pneumonia complicated by pleural effusion and an L4-L5 spondylodiscitis. Blood culture and pus drainage were positive for Fusobacterium nucleatum and an atypical Lemierre's syndrome was suspected. The patient was treated with anticoagulant therapy for 12 weeks and intravenous antibiotic therapy for 6 weeks with a good evolution and resolution of the thrombosis.

Conclusions: This case illustrates the thrombogenic and thromboembolic tendency of Fusobacterium nucleatum and its potential invasiveness, regardless of the site of primary infection. The concept of an atypical Lemierre's syndrome is redefined here to take into consideration non-cervical sites.
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http://dx.doi.org/10.1186/s12879-019-4538-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805316PMC
October 2019

Next-Generation Sequencing for the Diagnosis of Challenging Culture-Negative Endocarditis.

Front Med (Lausanne) 2019 20;6:203. Epub 2019 Sep 20.

Genomic Research Laboratory, Service of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.

Diagnosis of culture-negative infective endocarditis usually implies indirect pathogen identification by serologic or molecular techniques. Clinical metagenomics, relying on next-generation sequencing (NGS) is an emerging approach that allows pathogen identification in challenging situations, as evidenced by a clinical case. We sequenced the DNA extracted from the surgically-removed frozen valve tissue from a patient with suspected infective endocarditis with negative blood and valve cultures. Mapping of the sequence reads against reference genomic sequences, a 16S rRNA gene database and clade-specific marker genes suggested an infection caused by .
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http://dx.doi.org/10.3389/fmed.2019.00203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763761PMC
September 2019

Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis.

Cell Rep 2019 Oct;29(2):378-390.e4

Laboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. Electronic address:

Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the α4β7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in the Th17 cell adoptive transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gut microbiota composition. The beneficial effect of blocking the α4β7-integrin and its ligand MAdCAM-1 pathway on EAE is interdependent with gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harnesses neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cells.
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http://dx.doi.org/10.1016/j.celrep.2019.09.002DOI Listing
October 2019