21 results on '"Cattoir, Vincent"'
Search Results
2. High-level carbapenem tolerance requires antibiotic-induced outer membrane modifications.
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Murtha, Andrew N., Kazi, Misha I., Schargel, Richard D., Cross, Trevor, Fihn, Conrad, Cattoir, Vincent, Carlson, Erin E., Boll, Joseph M., and Dörr, Tobias
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ANTIBIOTICS ,MEROPENEM ,COLISTIN ,ELECTROSTATIC interaction ,PEPTIDES ,TREATMENT failure - Abstract
Antibiotic tolerance is an understudied potential contributor to antibiotic treatment failure and the emergence of multidrug-resistant bacteria. The molecular mechanisms governing tolerance remain poorly understood. A prominent type of β-lactam tolerance relies on the formation of cell wall-deficient spheroplasts, which maintain structural integrity via their outer membrane (OM), an asymmetric lipid bilayer consisting of phospholipids on the inner leaflet and a lipid-linked polysaccharide (lipopolysaccharide, LPS) enriched in the outer monolayer on the cell surface. How a membrane structure like LPS, with its reliance on mere electrostatic interactions to maintain stability, is capable of countering internal turgor pressure is unknown. Here, we have uncovered a novel role for the PhoPQ two-component system in tolerance to the β-lactam antibiotic meropenem in Enterobacterales. We found that PhoPQ is induced by meropenem treatment and promotes an increase in 4-amino-4-deoxy-L-aminoarabinose [L-Ara4N] modification of lipid A, the membrane anchor of LPS. L-Ara4N modifications likely enhance structural integrity, and consequently tolerance to meropenem, in several Enterobacterales species. Importantly, mutational inactivation of the negative PhoPQ regulator mgrB (commonly selected for during clinical therapy with the last-resort antibiotic colistin, an antimicrobial peptide [AMP]) results in dramatically enhanced tolerance, suggesting that AMPs can collaterally select for meropenem tolerance via stable overactivation of PhoPQ. Lastly, we identify histidine kinase inhibitors (including an FDA-approved drug) that inhibit PhoPQ-dependent LPS modifications and consequently potentiate meropenem to enhance lysis of tolerant cells. In summary, our results suggest that PhoPQ-mediated LPS modifications play a significant role in stabilizing the OM, promoting survival when the primary integrity maintenance structure, the cell wall, is removed. Author summary: Treating an infection with an antibiotic often fails, resulting in a tremendous public health burden. One understudied likely reason for treatment failure is the development of "antibiotic tolerance", the ability of bacteria to survive normally lethal exposure to an antibiotic. Here, we describe a molecular mechanism promoting tolerance. A bacterial stress sensor (PhoPQ) is activated in response to antibiotic (meropenem) treatment and consequently strengthens a bacterial protective "shell" to enhance survival. We also identify inhibitors of this mechanism, opening the door to developing compounds that help antibiotics work better against tolerant bacteria. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Activity of the combination of colistin and fosfomycin against NDM-1-producing Escherichia coli with variable levels of susceptibility to colistin and fosfomycin in a murine model of peritonitis.
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Menestrel, Alice Le, Guerin, François, Chau, Françoise, Massias, Laurent, Benchetrit, Laura, Cattoir, Vincent, Fantin, Bruno, Lastours, Victoire de, Le Menestrel, Alice, and de Lastours, Victoire
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FOSFOMYCIN ,COLISTIN ,ESCHERICHIA coli ,PERITONITIS ,COUNTING ,ANTIBIOTICS ,BIOLOGICAL models ,RESEARCH ,ACIDS ,ANIMAL experimentation ,RESEARCH methodology ,EVALUATION research ,HYDROLASES ,COMPARATIVE studies ,DRUG synergism ,MICE ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Abstract
Background: Alternative treatments are needed against NDM-1-producing Escherichia coli. Colistin (COL) and fosfomycin (FOS) often remain active in vitro but selection of resistant mutants is frequent if used separately. We determined whether the combination of colistin and fosfomycin may be useful to treat infections with NDM-1-producing E. coli with varying levels of resistance.Methods: Isogenic derivatives of E. coli CFT073 with blaNDM-1 and variable levels of resistance to colistin and fosfomycin (CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively) were used. The combination (colistin + fosfomycin) was tested in vitro and in a fatal peritonitis murine model. Mortality and bacterial loads were determined and resistant mutants detected.Results: Colistin MICs were 0.5, 16 and 0.5 mg/L and fosfomycin MICs were 1, 1 and 32 mg/L against CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively. In time-kill curves, combining colistin with fosfomycin was synergistic and bactericidal against CFT073-NDM1 and CFT073-NDM1-FOS, with concentrations of 4× MIC (for both drugs), but not against CFT073-NDM1-COL (concentrations of colistin = 0.5× MIC), due to regrowth with fosfomycin-resistant mutants. Mice died less and bacterial counts were lower in spleen with the combination compared with monotherapy against all strains; the combination prevented selection of resistant mutants except for CFT073-NDM1-COL where fosfomycin-resistant mutants were found in all mice.Conclusions: Combining colistin and fosfomycin was beneficial in vitro and in vivo against NDM-1-producing E. coli, even with strains less susceptible to colistin and fosfomycin. However, the combination failed to prevent the emergence of fosfomycin-resistant mutants against colistin-resistant strains. Combining colistin and fosfomycin constitutes an alternative for treatment of NDM-1 E. coli, except against colistin-resistant strains. [ABSTRACT FROM AUTHOR]- Published
- 2022
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4. Optimization of the rapid carbapenem inactivation method for use with AmpC hyperproducers.
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Muntean, Mădălina Maria, Muntean, Andrei-Alexandru, Guerin, François, Cattoir, Vincent, Creton, Elodie, Cotellon, Garance, Oueslati, Saoussen, Popa, Mircea Ioan, Girlich, Delphine, Iorga, Bogdan I., Bonnin, Rémy A., and Naas, Thierry
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SENSITIVITY & specificity (Statistics) ,CARBAPENEMS ,ANTIBIOTICS - Abstract
Objectives: Detection of carbapenemase-producing Enterobacterales (CPEs) is sometimes difficult with AmpC-hyperproducing Enterobacterales (AHEs), as they may falsely be classified as CPEs. Here, we present a rapid Carbapenem Inactivation Method (rCIM) optimized for AmpC producers (rCIM-A) that allows rapid and easy discrimination between AHEs and CPEs.Methods: Enterobacterales (n = 249), including natural AmpC producers, AHEs, CPEs and non-carbapenemase-producing carbapenem-resistant control strains were evaluated, using Carba NP, rCIM and rCIM-A. The rCIM-A differs from the rCIM by the addition of cloxacillin (400 μg/mL) to the initial antibiotic incubation step.Results: The rCIM-A yielded a sensitivity and specificity of 84.26% (95% CI: 76.00%-90.55%) and 99.29% (95% CI: 96.11%-99.98%), respectively, while those of the rCIM were 86.11% (95% CI: 78.13%-92.01%) and 80.85% (95% CI: 73.38%-86.99%), respectively; those of Carba NP were lower at 84.04% (95% CI: 75.05%-90.78%) and 91.37% (95% CI: 85.41%-95.46%), respectively, due to indeterminate results. The rCIM-A was capable of discriminating between AHEs and true CPEs, but still failed to identify OXA-23-producing Proteus mirabilis isolates and remained only partially reliable for identifying IMI-like producers and a few MBL (2 NDM-1, 1 LMB-1, 1 TMB-1 and 1 IMP-13) producers. One chromosomally encoded AmpC variant, MIR-10, gave repeatedly positive results using all three tests and was thus considered a false positive.Conclusions: Specificity for AHEs greatly improved with the rCIM-A without altering the test performance for the other resistance mechanisms. It may replace the rCIM as a cheap, easy, rapid and accurate CPE detection test. [ABSTRACT FROM AUTHOR]- Published
- 2021
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5. Genetic features of the poxtA linezolid resistance gene in human enterococci from France.
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Dejoies, Loren, Sassi, Mohamed, Schutz, Sacha, Moreaux, Julie, Zouari, Asma, Potrel, Sophie, Collet, Anaïs, Lecourt, Maxime, Auger, Gabriel, and Cattoir, Vincent
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ENTEROCOCCUS ,LINEZOLID ,HUMAN genes ,ENTEROCOCCUS faecalis ,PLASMIDS ,ENTEROCOCCUS faecium ,ENTEROCOCCAL infections ,RESEARCH ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,GRAM-positive bacterial infections ,COMPARATIVE studies ,RESEARCH funding ,DRUG resistance in microorganisms ,MICROBIAL sensitivity tests ,ANTIBIOTICS ,PHARMACODYNAMICS - Abstract
Objectives: To describe the prevalence of poxtA among clinical linezolid-resistant enterococci (LRE) collected in France from 2016 to 2020 and to extensively characterize its genetic supports and environments.Methods: All LRE clinical isolates received at the National Reference Centre for Enterococci from French hospitals between 2016 and 2020 were included. LRE isolates were screened for linezolid resistance genes (cfr-like, optrA and poxtA) by real-time PCR and phenotypically characterized. A collection of 11 representative poxtA-positive isolates (10 Enterococcus faecium and 1 Enterococcus faecalis) underwent WGS by hybrid assembly combining short-read (Illumina MiSeq) and long-read (MinION) approaches. Transferability of poxtA was attempted by filter-mating experiments.Results: Out of 466 LRE received at the National Reference Centre for Enterococci over the period, 47 (10.1%) were poxtA-positive, including 42 E. faecium. The 11 isolates characterized by WGS were confirmed to be epidemiologically unrelated by core genome analysis and eight different STs were assigned to E. faecium isolates. The poxtA gene was found to be plasmid carried and flanked by IS1216E transposase genes in all isolates and frequently linked with fexB, tet(M) and tet(L). A total of seven distinct poxtA-harbouring plasmids were obtained after hybrid assembly and plasmid transfer of poxtA was successful in three cases. For the two poxtA/optrA-positive isolates, those genes were carried by different plasmids.Conclusions: The poxtA gene has been circulating among clinical enterococci in France since at least 2016, mostly in E. faecium and independently from optrA. The poxtA-carrying plasmids often co-carried resistance genes to phenicols and tetracyclines, and could have been co-selected through their veterinary use. [ABSTRACT FROM AUTHOR]- Published
- 2021
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6. Use of rifampicin and graft removal are associated with better outcomes in prosthetic vascular graft infection.
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Coste, Anne, Poinot, Mélanie, Panaget, Sophie, Albert, Bénédicte, Kaladji, Adrien, Le Bars, Hervé, Bahaa, Nasr, Ali, Badra, Piau, Caroline, Cattoir, Vincent, de Moreuil, Claire, Revest, Matthieu, and Le Berre, Rozenn
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ANTIBIOTICS ,ACADEMIC medical centers ,CONFIDENCE intervals ,INFECTION ,COMPLICATIONS of prosthesis ,RIFAMPIN ,OPERATIVE surgery ,TRANSPLANTATION of organs, tissues, etc. ,DISEASE relapse ,TREATMENT effectiveness ,RETROSPECTIVE studies ,DESCRIPTIVE statistics ,ODDS ratio - Abstract
Objectives: Prosthetic vascular graft infection (PVGI) is a very severe disease. We aimed to determine the factors associated with treatment failure. Methods: Patients admitted to two University Hospitals with PVGI were included in this retrospective study. PVGI was classified as possible, probable or proven according to an original set of diagnostic criteria. We defined treatment failure if one of the following events occurred within the first year after PVGI diagnosis: death and infection recurrence due to the same or another pathogen. Results: One hundred and twelve patients were diagnosed with possible (n = 26), probable (n = 22) and proven (n = 64) PVGI. Bacterial documentation was obtained for 81% of patients. The most frequently identified pathogen was Staphylococcus aureus (n = 39). Surgery was performed in 96 patients (86%). Antibiotics were administered for more than 6 weeks in 41% of patients. Treatment failure occurred in 30 patients (27.5%). The factors associated with a lower probability of treatment failure were total removal of the infected graft (OR = 0.2, 95% CI [0.1–0.6]), rifampicin administration (OR = 0.3 [0.1–0.9]) and possible PVGI according to the GRIP criteria (OR = 0.3 [0.1–0.9]). Conclusions: Treatment failure occurred in 27.5% of patients with PVGI. Total removal of the infected graft and rifampicin administration were associated with better outcomes. [ABSTRACT FROM AUTHOR]
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- 2021
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7. ResFinder 4.0 for predictions of phenotypes from genotypes.
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Bortolaia, Valeria, Kaas, Rolf S, Ruppe, Etienne, Roberts, Marilyn C, Schwarz, Stefan, Cattoir, Vincent, Philippon, Alain, Allesoe, Rosa L, Rebelo, Ana Rita, Florensa, Alfred Ferrer, Fagelhauer, Linda, Chakraborty, Trinad, Neumann, Bernd, Werner, Guido, Bender, Jennifer K, Stingl, Kerstin, Nguyen, Minh, Coppens, Jasmine, Xavier, Basil Britto, and Malhotra-Kumar, Surbhi
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CAMPYLOBACTER jejuni ,ENTEROCOCCUS faecium ,FORECASTING ,GRAM-positive bacteria ,DRUG resistance in microorganisms ,GRAM-negative bacteria ,RESEARCH ,ANIMAL experimentation ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,GENOTYPES ,ANTIBIOTICS ,MICROBIAL sensitivity tests ,PHENOTYPES ,PHARMACODYNAMICS - Abstract
Objectives: WGS-based antimicrobial susceptibility testing (AST) is as reliable as phenotypic AST for several antimicrobial/bacterial species combinations. However, routine use of WGS-based AST is hindered by the need for bioinformatics skills and knowledge of antimicrobial resistance (AMR) determinants to operate the vast majority of tools developed to date. By leveraging on ResFinder and PointFinder, two freely accessible tools that can also assist users without bioinformatics skills, we aimed at increasing their speed and providing an easily interpretable antibiogram as output.Methods: The ResFinder code was re-written to process raw reads and use Kmer-based alignment. The existing ResFinder and PointFinder databases were revised and expanded. Additional databases were developed including a genotype-to-phenotype key associating each AMR determinant with a phenotype at the antimicrobial compound level, and species-specific panels for in silico antibiograms. ResFinder 4.0 was validated using Escherichia coli (n = 584), Salmonella spp. (n = 1081), Campylobacter jejuni (n = 239), Enterococcus faecium (n = 106), Enterococcus faecalis (n = 50) and Staphylococcus aureus (n = 163) exhibiting different AST profiles, and from different human and animal sources and geographical origins.Results: Genotype-phenotype concordance was ≥95% for 46/51 and 25/32 of the antimicrobial/species combinations evaluated for Gram-negative and Gram-positive bacteria, respectively. When genotype-phenotype concordance was <95%, discrepancies were mainly linked to criteria for interpretation of phenotypic tests and suboptimal sequence quality, and not to ResFinder 4.0 performance.Conclusions: WGS-based AST using ResFinder 4.0 provides in silico antibiograms as reliable as those obtained by phenotypic AST at least for the bacterial species/antimicrobial agents of major public health relevance considered. [ABSTRACT FROM AUTHOR]- Published
- 2020
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8. Performance of commercial methods for linezolid susceptibility testing of Enterococcus faecium and Enterococcus faecalis.
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Dejoies, Loren, Boukthir, Sarrah, Péan de Ponfilly, Gauthier, Le Guen, Ronan, Zouari, Asma, Potrel, Sophie, Collet, Anaïs, Auger, Gabriel, Jacquier, Hervé, Fihman, Vincent, Dortet, Laurent, and Cattoir, Vincent
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RESEARCH ,ENTEROCOCCUS faecium ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,GRAM-positive bacterial infections ,COMPARATIVE studies ,ENTEROCOCCUS ,DRUG resistance in microorganisms ,ANTIBIOTICS ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Abstract
Background: Linezolid-resistant enterococci (LRE) causing infections that are challenging to treat are rising, highlighting the need for reliable screening of LRE clinical isolates.Objectives: To evaluate the ability of the broth microdilution (BMD) method for LRE detection and to assess the performance of seven commercially available techniques for linezolid susceptibility testing.Methods: A collection of 100 clinical isolates (80 Enterococcus faecium and 20 Enterococcus faecalis), including 20 optrA-positive isolates, 17 poxtA-positive isolates and 1 optrA/poxtA-positive E. faecium isolate, were studied. MICs were determined after 18 h [Day 1 (D1)] and 42 h [Day 2 (D2)] of incubation and interpreted following EUCAST and CLSI guidelines, which currently provide different interpretative breakpoints. Performance of commercial techniques was compared with BMD results.Results: MIC50/D1 and MIC50/D2 were both 8 mg/L, while MIC90/D1 and MIC90/D2 were 16 and 32 mg/L, respectively. MICD1 values for poxtA-positive isolates were lower than those for optrA-positive isolates. Proportions of susceptible isolates at D1 and D2 were 48% and 41%, respectively, according to EUCAST breakpoints and 35% and 13%, respectively, according to CLSI criteria (the proportions of isolates categorized as intermediate following CLSI recommendations were 13% and 28% at D1 and D2, respectively). Percentage susceptibility assessed by the commercially available techniques was always higher. The four commercial methods allowing MIC determination provided an overall essential agreement of ≥90% at D1. Categorical agreement and error rates were generally improved at D2.Conclusions: Non-automated methods (Sensititre and UMIC) and, to a lesser extent, gradient strip Etest appear to show an acceptable correlation with the BMD reference method for the detection of isolates with low MICs of linezolid after prolonged incubation. [ABSTRACT FROM AUTHOR]- Published
- 2020
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9. Molecular and functional analysis of the novel cfr(D) linezolid resistance gene identified in Enterococcus faecium.
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Guerin, François, Sassi, Mohamed, Dejoies, Loren, Zouari, Asma, Schutz, Sacha, Potrel, Sophie, Auzou, Michel, Collet, Anaïs, Lecointe, Didier, Auger, Gabriel, and Cattoir, Vincent
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PROTEINS ,ESCHERICHIA coli ,RESEARCH ,ENTEROCOCCUS faecium ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,GRAM-positive bacterial infections ,COMPARATIVE studies ,ENTEROCOCCUS ,TRANSFERASES ,DRUG resistance in microorganisms ,ANTIBIOTICS ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Abstract
Objectives: To characterize the novel cfr(D) gene identified in an Enterococcus faecium clinical isolate (15-307.1) collected from France.Methods: The genome of 15-307.1 was entirely sequenced using a hybrid approach combining short-read (MiSeq, Illumina) and long-read (GridION, Oxford Nanopore Technologies) technologies in order to analyse in detail the genetic support and environment of cfr(D). Transfer of linezolid resistance from 15-307.1 to E. faecium BM4107 was attempted by filter-mating experiments. The recombinant plasmid pAT29Ωcfr(D), containing cfr(D) and its own promoter, was transferred to E. faecium HM1070, Enterococcus faecalis JH2-2 and Escherichia coli AG100A.Results: As previously reported, 15-307.1 belonged to ST17 and was phenotypically resistant to linezolid (MIC, 16 mg/L), vancomycin and teicoplanin. A hybrid sequencing approach confirmed the presence of several resistance genes including vanA, optrA and cfr(D). Located on a 103 kb plasmid, cfr(D) encoded a 357 amino acid protein, which shared 64%, 64%, 48% and 51% amino acid identity with Cfr, Cfr(B), Cfr(C) and Cfr(E), respectively. Both optrA and cfr(D) were successfully co-transferred to E. faecium BM4107. When expressed in E. faecium HM1070 and E. faecalis JH2-2, pAT29Ωcfr(D) did not confer any resistance, whereas it was responsible for an expected PhLOPSA resistance phenotype in E. coli AG100A. Analysis of the genetic environment of cfr(D) showed multiple IS1216 elements, putatively involved in its mobilization.Conclusions: Cfr(D) is a novel member of the family of 23S rRNA methyltransferases. While only conferring a PhLOPSA resistance phenotype when expressed in E. coli, enterococci could constitute an unknown reservoir of cfr(D). [ABSTRACT FROM AUTHOR]- Published
- 2020
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10. Helcococcus kunzii methyltransferase Erm(47) responsible for MLSB resistance is induced by diverse ribosome-targeting antibiotics.
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Guerin, François, Rose, Simon, Cattoir, Vincent, and Douthwaite, Stephen
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ANTIBIOTICS ,BINDING sites ,DRUG resistance ,DOSAGE forms of drugs ,LINEZOLID ,RIBOSOMAL proteins ,ERYTHROMYCIN ,RIBOSOMAL RNA - Abstract
Objectives: To determine the mechanism of induction of erm(47) and its atypical expression in the Gram-positive opportunistic pathogen Helcococcus kunzii, where it confers resistance to a subset of clinically important macrolide, lincosamide and streptogramin B (MLSB) antibiotics.Methods: The resistant H. kunzii clinical isolate UCN99 was challenged with subinhibitory concentrations of a wide range of ribosome-targeting drugs. The methylation status of the H. kunzii ribosomal RNA at the MLSB binding site was then determined using an MS approach and was correlated with any increase in resistance to the drugs.Results: The H. kunzii erm(47) gene encodes a monomethyltransferase. Expression is induced by subinhibitory concentrations of the macrolide erythromycin, as is common for many erm genes, and surprisingly also by 16-membered macrolide, lincosamide, streptogramin, ketolide, chloramphenicol and linezolid antibiotics, all of which target the 50S ribosomal subunit. No induction was detected with spectinomycin, which targets the 30S subunit.Conclusions: The structure of the erm(47) leader sequence functions as a hair trigger for the induction mechanism that expresses resistance. Consequently, translation of the erm(47) mRNA is tripped by MLSB compounds and also by drugs that target the 50S ribosomal subunit outside the MLSB site. Expression of erm(47) thus extends previous assumptions about how erm genes can be induced. [ABSTRACT FROM AUTHOR]- Published
- 2020
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11. Genetic characterization of a VanG-type vancomycin-resistant Enterococcus faecium clinical isolate.
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Sassi, Mohamed, Guérin, François, Lesec, Léonie, Isnard, Christophe, Fines-Guyon, Marguerite, Cattoir, Vincent, and Giard, Jean-Christophe
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ANTIBIOTICS ,CHROMOSOMES ,ERYTHROMYCIN ,GENE expression ,POLYMERASE chain reaction ,RIFAMPIN ,TETRACYCLINE ,VANCOMYCIN ,PHENOTYPES ,VANCOMYCIN resistance ,REVERSE transcriptase polymerase chain reaction ,ENTEROCOCCUS faecium ,SEQUENCE analysis ,GENOTYPES - Abstract
Objectives: To characterize, phenotypically and genotypically, the first Enterococcus faecium clinical isolate harbouring a vanG operon.Methods: The antibiotic resistance profile of E. faecium 16-346 was determined and its whole genome sequenced using PacBio technology. Attempts to transfer vancomycin resistance by filter mating were performed and the inducibility of expression of the vanG operon was studied by reverse-transcription quantitative PCR (RT-qPCR) in the presence or absence of subinhibitory concentrations of vancomycin.Results: E. faecium 16-346 was resistant to rifampicin (MIC >4 mg/L), erythromycin (MIC >4 mg/L), tetracycline (MIC >16 mg/L) and vancomycin (MIC 8 mg/L), but susceptible to teicoplanin (MIC 0.5 mg/L). The strain harboured the vanG operon in its chromosome, integrated in a 45.5 kb putative mobile genetic element, similar to that of Enterococcus faecalis BM4518. We were unable to transfer vancomycin resistance from E. faecium 16-346 to E. faecium BM4107 and E. faecalis JH2-2. Lastly, transcription of the vanG gene was inducible by vancomycin.Conclusions: This is, to the best of our knowledge, the first report of a VanG-type vancomycin-resistant strain of E. faecium. Despite the alarm pulled because of the therapeutic problems caused by VRE, our work shows that new resistant loci can still be found in E. faecium. [ABSTRACT FROM AUTHOR]- Published
- 2018
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12. Optimization of the rapid carbapenem inactivation method for use with AmpC hyperproducers-authors' response.
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Muntean, Mădălina Maria, Muntean, Andrei-Alexandru, Guerin, François, Cattoir, Vincent, Creton, Elodie, Cotellon, Garance, Oueslati, Saoussen, Popa, Mircea Ioan, Girlich, Delphine, Iorga, Bogdan I., Bonnin, Rémy A., and Naas, Thierry
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ANTIBIOTICS ,BACTERIAL proteins ,HYDROLASES ,CARBAPENEMS ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Published
- 2022
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13. Novel chromosome-encoded erm(47) determinant responsible for constitutive MLSB resistance in Helcococcus kunzii.
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Guérin, François, Isnard, Christophe, Bucquet, Fiona, Fines-Guyon, Marguerite, Giard, Jean-Christophe, Burrus, Vincent, and Cattoir, Vincent
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DRUG resistance in bacteria ,DRUG resistance in microorganisms ,ERYTHROMYCIN ,DALFOPRISTIN ,STREPTOGRAMINS ,ANTIBIOTICS ,CHROMOSOMES ,DNA ,GENE expression ,GENES ,GENETIC techniques ,GLYCOSIDES ,MACROLIDE antibiotics ,MICROBIAL sensitivity tests ,PEPTIDES ,STAPHYLOCOCCUS aureus ,STREPTOCOCCUS ,SEQUENCE analysis ,PHARMACODYNAMICS - Abstract
Objectives: The aim of the study was to identify the determinant responsible for erythromycin resistance in Helcococcus kunzii clinical isolate UCN99 and to characterize the genetic support and environment of this novel gene.Methods: MICs were determined using the broth microdilution method according to EUCAST guidelines. The entire genome sequence of H. kunzii UCN99 was determined using a 454/Roche GS Junior sequencer. The fragment encompassing the new resistance gene and its own promoter was cloned into the pAT29 shuttle vector and the recombinant plasmid pAT29Ωerm(47) was expressed in both Staphylococcus aureus and Streptococcus agalactiae. The transcription start site (TSS) was experimentally determined by 5' RACE-PCR.Results: UCN99 exhibited a constitutive macrolide/lincosamide/streptogramin B (MLSB) resistance phenotype, suggesting the presence of an Erm protein. WGS allowed the identification of a novel gene, named erm(47), encoding a protein sharing 44%-48% amino acid identity with known Erm methylases. In both S. aureus and S. agalactiae, the introduction of pAT29Ωerm(47) conferred a significant increase (≥16-fold) in MICs of all macrolides and lincosamides tested, as well as a 4-fold increase in MICs of quinupristin (streptogramin B), confirming the MLSB resistance. The TSS identification revealed the presence of a short leader peptide, potentially implicated in a translational attenuation mechanism. It was also demonstrated that erm(47) was harboured by a 81 kb genomic island integrated into a chromosomal gene.Conclusions: This is the first description of a novel MLSB resistance determinant, named erm(47). The prevalence of this gene among Gram-positive cocci must be further investigated to determine its clinical significance. [ABSTRACT FROM AUTHOR]- Published
- 2016
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14. Cluster-dependent colistin hetero-resistance in Enterobacter cloacae complex.
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Guérin, François, Isnard, Christophe, Sinel, Clara, Morand, Philippe, Dhalluin, Anne, Cattoir, Vincent, and Giard, Jean-Christophe
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ENTEROBACTER cloacae ,COLISTIN ,POLYMYXIN ,ENTEROBACTER ,DRUG resistance in bacteria ,ANTIBIOTICS ,DRUG resistance in microorganisms ,GENES ,GRAM-negative bacteria ,MICROBIAL sensitivity tests ,GENETIC mutation ,ENTEROBACTERIACEAE diseases ,GENOTYPES ,PHARMACODYNAMICS - Abstract
Objectives: Aims of this study were to: (i) evaluate whether the cluster membership could have an impact on hetero-resistance phenotype to colistin in the Enterobacter cloacae complex (ECC); and (ii) determine the genetic mechanism of colistin hetero-resistance in ECC.Methods: A collection of 124 clinical isolates belonging to 13 clusters were used to analyse the hetero-resistance phenotype (MICs were determined using the broth microdilution method, Etest and population analysis profiling). Different mutants (ΔphoP, ΔphoQ, ΔphoPQ, ΔpmrA, ΔpmrB, ΔpmrAB, ΔarnE, ΔarnF and ΔarnBCADTEF) were constructed and tested for their colistin hetero-resistance phenotype.Results: Based on broth microdilution and Etest results, it was shown that the hetero-resistance to colistin depended on the cluster: strains from clusters I, II, IV, VII, IX, X, XI and XII were usually hetero-resistant, whereas those from clusters III, V, VI, VIII and XIII were categorized as susceptible. However, for some cluster V and VIII strains, a small proportion (<10-7) of cells appeared resistant when tested by population analysis profiling. From a mechanistic point of view, analysis of mutants revealed that the mechanism of hetero-resistance was mainly due to the expression of the arn operon and the phoP/phoQ two-component regulatory system.Conclusions: Because the colistin hetero-resistance appeared cluster-dependent in the ECC, it should be advocated to determine the cluster of the strain associated with the infection in parallel with the MIC of colistin. The resistance mechanism may not be similar to other Enterobacteriaceae since only the two-component regulatory system PhoP/PhoQ (and not PmrA/PmrB) seemed to play a role in resistance regulation. [ABSTRACT FROM AUTHOR]- Published
- 2016
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15. A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii.
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Boll, Joseph M., Crofts, Alexander A., Peters, Katharina, Cattoir, Vincent, Vollmer, Waldemar, Davies, Bryan W., and Trent, M. Stephen
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GRAM-negative bacteria ,BACTERIA ,ANTIBIOTICS ,GLYCOLIPIDS ,LIPOPOLYSACCHARIDES ,LIPOOLIGOSACCHARIDES ,CELL membranes - Abstract
The Gram-negative bacterial outer membrane fortifies the cell against environmental toxins including antibiotics. Unique glycolipids called lipopolysaccharide/lipooligosaccharide (LPS/LOS) are enriched in the cell-surface monolayer of the outer membrane and promote antimicrobial resistance. Colistin, which targets the lipid A domain of LPS/LOS to lyse the cell, is the last-line treatment for multidrug-resistant Gram-negative infections. Lipid A is essential for the survival of most Gram-negative bacteria, but colistin-resistant Acinetobacter baumannii lacking lipid A were isolated after colistin exposure. Previously, strain ATCC 19606 was the only A. baumannii strain demonstrated to subsist without lipid A. Here, we show that other A. baumannii strains can also survive without lipid A, but some cannot, affording a unique model to study endotoxin essentiality. We assessed the capacity of 15 clinical A. baumannii isolates including 9 recent clinical isolates to develop colistin resistance through inactivation of the lipid A biosynthetic pathway, the products of which assemble the LOS precursor. Our investigation determined that expression of the well-conserved penicillin-binding protein (PBP) 1A, prevented LOS-deficient colony isolation. The glycosyltransferase activity of PBP1A, which aids in the polymerization of the peptidoglycan cell wall, was lethal to LOS-deficient A. baumannii. Global transcriptomic analysis of a PBP1A-deficient mutant and four LOS-deficient A. baumannii strains showed a concomitant increase in transcription of lipoproteins and their transporters. Examination of the LOS-deficient A. baumannii cell surface demonstrated that specific lipoproteins were overexpressed and decorated the cell surface, potentially compensating for LOS removal. This work expands our knowledge of lipid A essentiality and elucidates a drug resistance mechanism. [ABSTRACT FROM AUTHOR]
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- 2016
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16. Sequential steps of daptomycin resistance in Enterococcus faecium and reversion to hypersusceptibility through IS-mediated inactivation of the liaFSR operon.
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Sinel, Clara, Cosquer, Thibaud, Auzou, Michel, Goux, Didier, Giard, Jean-Christophe, and Cattoir, Vincent
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ENTEROCOCCUS faecium ,ANAPHYLAXIS ,NUCLEOTIDE sequencing ,GENETIC mutation ,REVERTANTS (Genetics) ,AMINO acids ,ANTIBIOTICS ,BACTERIAL proteins ,DNA ,DRUG resistance in microorganisms ,GENOMES ,MICROBIAL sensitivity tests ,PEPTIDE antibiotics ,VANCOMYCIN resistance ,PHARMACODYNAMICS - Abstract
Objectives: To improve understanding of mechanisms of daptomycin resistance and to dissect the genetic basis of reversion to daptomycin hypersusceptibility in Enterococcus faecium.Methods: Daptomycin-resistant mutants (Mut4, Mut8, Mut16, Mut32, Mut64 and Mut128 with MICs from 4 to 128 mg/L) were obtained in vitro from E. faecium strain Aus0004 (MIC at 2 mg/L). The entire genome sequences of Mut64 and Mut128 were determined as well as those of liaFSR and cls genes for other mutants and corresponding revertants (named Rev4 to Rev128). The study of daptomycin resistance stability was performed without any selective pressure. The expression of liaF, liaS and liaR genes was quantified by quantitative RT-PCR.Results: By comparative genomic analysis, substitutions Asn13Ser in cls and Gly92Asp in liaS were identified in Mut64 and Mut128. Only the liaS mutation was found in Mut16 and Mut32 while Mut4 and Mut8 were devoid of any mutation. After 15 days, all mutants except Mut4 reverted to daptomycin hypersusceptibility (MICs from 0.12 to 0.25 mg/L). In all revertants (except Rev4 and Rev8), an IS was found in the liaFSR operon with a dramatic decrease of its expression: IS66 in the promoter region of liaF (Rev16 and Rev64), IS30 in liaR (Rev32) and IS982 in liaF (Rev128).Conclusions: We demonstrated the stepwise and sequential acquisition of mutations in liaS and in cls leading to daptomycin resistance in E. faecium, and the instability of daptomycin resistance as well as the role of liaFSR inactivation in reversion to daptomycin hypersusceptibility. [ABSTRACT FROM AUTHOR]- Published
- 2016
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17. Study on daptomycin use and implementation of an antimicrobial stewardship program.
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Castel, Camille, Blanchardière, Arnaud, Michon, Jocelyn, Cattoir, Vincent, Saint-Lorant, Guillaume, and de La Blanchardière, Arnaud
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PHARMACEUTICAL research ,DRUG utilization ,ANTI-infective agents ,METHICILLIN-resistant staphylococcus aureus ,VANCOMYCIN resistance ,ANTIBIOTICS ,STAPHYLOCOCCAL disease prevention ,PEPTIDE antibiotics ,INAPPROPRIATE prescribing (Medicine) ,HEALTH care teams ,INTERPROFESSIONAL relations ,RETROSPECTIVE studies ,STAPHYLOCOCCAL diseases ,DIAGNOSIS ,PREVENTION ,THERAPEUTICS - Abstract
Background: Treatment of Gram-positive pathogens remains a major health issue due to the presence of methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus spp. Daptomycin offers an alternative after therapeutic failure using glycopeptides. Yet its use requires strict control given its financial impact and environmental risks. Since 2014, the use of daptomycin within our hospital has intensified, occasionally outside the scope of its approved indications.Objectives: The aim of this study is to analyze the appropriateness of daptomycin prescriptions.Setting: This work was conducted in a 1500-bed University Hospital.Method: A descriptive retrospective study was conducted from November 2013 to July 2014. All patients having received at least 2 days of treatment were included. Analysis of the appropriateness of daptomycin prescriptions was conducted by a multidisciplinary team comprised of infectious diseases specialists, pharmacists and a microbiologist. The appropriateness of daptomycin prescriptions was established based on Infectious Diseases Society of America recommendations published in 2011.Main Outcome Measures: The indicators chosen to determine appropriateness of prescription were: treatment indication, prescribed dose and other antibiotics associated with the daptomycin prescription.Results: 19 patients (14 men/5 women) were included. Observed indications were: bone and joint infection (n = 6; 32 %), infectious endocarditis (n = 5; 26 %), bacteremia (n = 5; 26 %) and complicated skin and soft tissue infection (n = 3; 16 %). Identified pathogens were: MRSA (n = 14; 74 %), methicillin-resistant coagulase-negative Staphylococcus (n = 4; 21 %) and Streptococcus mitis (n = 1; 5 %). Daptomycin was prescribed as first-line treatment in 32 % of cases (n = 6). The mean dosage was 9 mg/kg/day (5-11 mg/kg/day) for a mean duration of 11 days (2; 55 days). Clinical success was observed in 42 % of cases (n = 8). Appropriateness for daptomycin use was only established for 15 % of prescriptions (n = 3).Conclusion: Faced with a lack of recent recommendations on the subject, our multidisciplinary team issued a local consensus, defining the indications and dosage modalities for this reserve antibiotic. This multidisciplinary approach enables improved use of recent anti-MRSA drugs. [ABSTRACT FROM AUTHOR]- Published
- 2016
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18. Bactéries à Gram positif et glycopeptides.
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Leclercq, Roland and Cattoir, Vincent
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GRAM-positive bacteria ,GLYCOPEPTIDES ,VANCOMYCIN ,TEICOPLANIN ,STAPHYLOCOCCUS ,ANTIBIOTICS - Abstract
Copyright of Revue Francophone des Laboratoires is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2012
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19. Intrinsic colistin resistance.
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Zhou, Kai, Cattoir, Vincent, and Xiao, Yonghong
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COLISTIN , *LIPOPOLYSACCHARIDES , *ATOMIC force microscopy , *BLOOD sampling , *GENOMES , *THERAPEUTICS , *ANTIBIOTICS , *DRUG resistance in microorganisms , *ESCHERICHIA coli , *GRAM-negative bacteria , *KLEBSIELLA , *BACTERIAL capsules , *PHARMACODYNAMICS - Published
- 2016
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20. A novel genomic island harbouring lsa(E), lnu(B) genes and a defective prophage in a Streptococcus pyogenes isolate resistant to lincosamide, streptogramin A and pleuromutilin antibiotics
- Author
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François Guérin, Vincent Cattoir, Carmen Ardanuy, Dàmaris Berbel, Ernesto García, Jordi Càmara, M. Angeles Domínguez, Jean-Christophe Giard, Fe Tubau, Jonchère, Laurent, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Fondo de Investigaciones Sanitarias de la Seguridad Social (INT 15/0186, INT16/0117 and PI18/00339), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES CB06/06/0037), European Regional Development Fund, CERCA Programme, Instituto de Salud Carlos III, European Commission, García, Ernesto [0000-0002-1741-5486], Tubau, Fe [0000-0002-6416-6451], Giard, Jean-Christophe [0000-0001-8588-2732], Cattoir, Vincent [0000-0003-4026-9912], Ardanuy, Carmen [0000-0003-0225-607X], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), García, Ernesto, Tubau, Fe, Giard, Jean-Christophe, Cattoir, Vincent, and Ardanuy, Carmen
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0301 basic medicine ,Prophages ,[SDV]Life Sciences [q-bio] ,medicine.disease_cause ,chemistry.chemical_compound ,0302 clinical medicine ,Antibiotics ,Genomic island ,Drug Resistance, Multiple, Bacterial ,lsa(E) ,Pharmacology (medical) ,030212 general & internal medicine ,Streptogramin A ,Streptococcus ,Defective Viruses ,General Medicine ,LS(A)P phenotype ,3. Good health ,Anti-Bacterial Agents ,Fenotip ,[SDV] Life Sciences [q-bio] ,Infectious Diseases ,Phenotype ,GAS ,Diterpenes ,Microbiology (medical) ,Transposable element ,DNA, Bacterial ,Genomic Islands ,Streptococcus pyogenes ,030106 microbiology ,Antibiòtics ,Microbial Sensitivity Tests ,Biology ,Microbiology ,03 medical and health sciences ,medicine ,Humans ,Polycyclic Compounds ,Lincosamides ,Gene ,Prophage ,Whole Genome Sequencing ,lnu(B) ,Estreptococs ,chemistry ,L phenotype ,Pleuromutilin ,Genome, Bacterial - Abstract
19 p.-1 fig., A lincosamide-resistant and macrolide-susceptible phenotype has not been described to date in Streptococcus pyogenes [group A streptococcus (GAS)]. The aim of this study was to characterize a GAS isolate susceptible to macrolides but resistant to lincosamide, streptogramin A and pleuromutilin antibiotics. Antimicrobial susceptibility was tested using the microdilution broth method and the resistance phenotype was tested by D-test. The GAS2887HUB isolate was subjected to whole-genome sequencing. The isolate showed a positive Gots' test (clindamycin inactivation). Whole-genome sequencing revealed that the strain was ST10 and emm93, and had five resistance genes [lnu(B), ant(6)-Ia, aph(3')-III, tet(M) and dfrG]. The tet(M) gene was located in a Tn916-like transposon. The lsa(E)-lnu(B)-containing sequence (inserted downstream of the rumA gene) was formed by a 39.6-kb prophage, followed by a gene cluster encoding aminoglycoside-streptothricin resistance [ant(6)Ia-sat4-aph(3')III] and lsa(E)-lnu(B) genes. This structure was not transferred by conjugation. This study identified a new genetic element carrying a determinant of lincosamide resistance in a GAS. Further molecular epidemiological surveys are needed to determine the prevalence of this mechanism of resistance in GAS., This study was supported by grants from Fondo de Investigaciones Sanitarias de la Seguridad Social (INT 15/0186; INT16/0117 and PI18/00339) and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES CB06/06/0037), an initiative of the Instituto de Salud Carlos III, Madrid, Spain. Financial support was also provided by the European Regional Development Fund and by CERCA Programme.
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- 2019
21. A novel genomic island harbouring lsa(E) and lnu(B) genes and a defective prophage in a Streptococcus pyogenes isolate resistant to lincosamide, streptogramin A and pleuromutilin antibiotics.
- Author
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Berbel, Dàmaris, Càmara, Jordi, García, Ernesto, Tubau, Fe, Guérin, François, Giard, Jean-Christophe, Domínguez, M. Ángeles, Cattoir, Vincent, and Ardanuy, Carmen
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- *
STREPTOCOCCUS , *STREPTOCOCCUS pyogenes , *ANTIBIOTICS , *MICROBIAL sensitivity tests , *GENES , *GENE clusters - Abstract
A lincosamide-resistant and macrolide-susceptible phenotype has not been described to date in Streptococcus pyogenes [group A streptococcus (GAS)]. The aim of this study was to characterize a GAS isolate susceptible to macrolides but resistant to lincosamide, streptogramin A and pleuromutilin antibiotics. Antimicrobial susceptibility was tested using the microdilution broth method and the resistance phenotype was tested by D-test. The GAS2887HUB isolate was subjected to whole-genome sequencing. The isolate showed a positive Gots' test (clindamycin inactivation). Whole-genome sequencing revealed that the strain was ST10 and emm 93, and had five resistance genes [ lnu (B) , ant (6)-Ia , aph (3′)-III, tet (M) and dfrG ]. The tet (M) gene was located in a Tn 916 -like transposon. The lsa (E)− lnu (B) - containing sequence (inserted downstream of the rumA gene) was formed by a 39.6-kb prophage, followed by a gene cluster encoding aminoglycoside–streptothricin resistance [ ant (6)Ia− sat4 − aph (3′)III] and lsa (E)− lnu (B) genes. This structure was not transferred by conjugation. This study identified a new genetic element carrying a determinant of lincosamide resistance in a GAS. Further molecular epidemiological surveys are needed to determine the prevalence of this mechanism of resistance in GAS. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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