The Experts below are selected from a list of 12453 Experts worldwide ranked by ideXlab platform
Steven E Bosinger - One of the best experts on this subject based on the ideXlab platform.
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antibiotic failure mediated by a resistant subpopulation in Enterobacter Cloacae
Nature microbiology, 2016Co-Authors: Victor I Band, Emily K Crispell, Brooke A Napier, Carmen M Herrera, Greg K Tharp, Kranthi Vavikolanu, Jan Pohl, Timothy D Read, Steven E BosingerAbstract:Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter Cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics. An undetected, phenotypically colistin-resistant subpopulation of Enterobacter Cloacae mediates antibiotic treatment failure
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antibiotic failure mediated by a resistant subpopulation in Enterobacter Cloacae
Nature microbiology, 2016Co-Authors: Victor I Band, Emily K Crispell, Brooke A Napier, Carmen M Herrera, Greg K Tharp, Kranthi Vavikolanu, Jan Pohl, Timothy D Read, Steven E BosingerAbstract:Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter Cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics.
Jeanchristophe Giard - One of the best experts on this subject based on the ideXlab platform.
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cluster dependent colistin hetero resistance in Enterobacter Cloacae complex
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Francois Guerin, Christophe Isnard, Clara Sinel, Philippe Morand, Anne Dhalluin, Vincent Cattoir, Jeanchristophe GiardAbstract: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.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.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.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.
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cluster dependent colistin hetero resistance in Enterobacter Cloacae complex
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Francois Guerin, Christophe Isnard, Clara Sinel, Philippe Morand, Anne Dhalluin, Vincent Cattoir, Jeanchristophe GiardAbstract: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.
Annecatrin Uhlemann - One of the best experts on this subject based on the ideXlab platform.
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multidrug resistant Enterobacter Cloacae complex emerging as a global diversifying threat
Frontiers in Microbiology, 2019Co-Authors: Medini K Annavajhala, Angela Gomezsimmonds, Annecatrin UhlemannAbstract:The Enterobacter Cloacae complex (ECC) includes common nosocomial pathogens capable of producing a wide variety of infections. Broad-spectrum antibiotic resistance, including the recent emergence of resistance to last-resort carbapenems, has led to increased interest in this group of organisms and carbapenem-resistant E. Cloacae complex (CREC) in particular. Molecular typing methods based on heat-shock protein sequence, pulsed-field gel electrophoresis, comparative genomic hybridization, and, most recently, multilocus sequence typing have led to the identification of over 1069 ECC sequence types in 18 phylogenetic clusters across the globe. Whole-genome sequencing and comparative genomics, moreover, have facilitated global analyses of clonal composition of ECC and specifically of CREC. Epidemiological and genomic studies have revealed diverse multidrug-resistant ECC clones including several potential epidemic lineages. Together with intrinsic β-lactam resistance, members of the ECC exhibit a unique ability to acquire genes encoding resistance to multiple classes of antibiotics, including a variety of carbapenemase genes. In this review, we address recent advances in the molecular epidemiology of multidrug-resistant E. Cloacae complex, focusing on the global expansion of CREC.
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multidrug resistant Enterobacter Cloacae complex emerging as a global diversifying threat
Frontiers in Microbiology, 2019Co-Authors: Medini K Annavajhala, Angela Gomezsimmonds, Annecatrin UhlemannAbstract:The Enterobacter Cloacae complex (ECC) includes common nosocomial pathogens capable of producing a wide variety of infections. Broad-spectrum antibiotic resistance, including the recent emergence of resistance to last-resort carbapenems, has led to increased interest in this group of organisms and carbapenem-resistant E. Cloacae complex (CREC) in particular. Molecular typing methods based on heat-shock protein (Hsp) sequence, pulsed-field gel electrophoresis (PFGE), comparative genomic hybridization (CGH), and, most recently, multilocus sequence typing (MLST) have led to the identification of over 1069 ECC sequence types (STs) in 18 phylogenetic clusters across the globe. Whole-genome sequencing (WGS) and comparative genomics, moreover, have facilitated global analyses of clonal composition of ECC and specifically of CREC. Epidemiological and genomic studies have revealed diverse multidrug-resistant ECC clones including several potential epidemic lineages. Together with intrinsic β-lactam resistance, members of the ECC exhibit a unique ability to acquire genes encoding resistance to multiple classes of antibiotics, including a variety of carbapenemase genes. In this review, we address recent advances in the molecular epidemiology of multidrug-resistant E. Cloacae complex, focusing on the global expansion of CREC.
Patrice Nordmann - One of the best experts on this subject based on the ideXlab platform.
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clonal distribution of multidrug resistant Enterobacter Cloacae
Diagnostic Microbiology and Infectious Disease, 2015Co-Authors: Delphine Girlich, Laurent Poirel, Patrice NordmannAbstract:A multilocus sequence typing (MLST) scheme including 7 housekeeping genes was used to evaluate whether the current spread of multidrug-resistant Enterobacter Cloacae isolates worldwide might be associated to specific successful clones. Fifty E. Cloacae clinical isolates of worldwide origin, with various β-lactamase content, and recovered at different periods of time were studied. Forty-four sequence types were identified, highlighting a high clonal diversity with 3 main lineages. This study revealed that a precise identification of the isolates by sequencing of the chromosomal ampC gene of E. Cloacae would provide a significant added value to improve the reliability of the MLST scheme.
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detection of the carbapenemase gim 1 in Enterobacter Cloacae in germany
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Axel Hamprecht, Laurent Poirel, Stephan Gottig, Harald Seifert, Martin Kaase, Patrice NordmannAbstract:Objectives To characterize the mechanisms involved in reduced susceptibility to carbapenems in two Enterobacter Cloacae clinical isolates. Methods Two E. Cloacae isolates recovered from different regions in Germany and showing reduced susceptibility to carbapenems were analysed. Susceptibility testing, conjugation, transformation assays, plasmid analysis, sequencing and molecular typing using rep-PCR were performed. Results The two clinical isolates carried the bla(GIM-1) gene and showed resistance to ertapenem, with variable MIC values of imipenem and meropenem. The isolates were clonally unrelated. The bla(GIM-1) gene was located on self-transferable and non-typeable plasmids. Both isolates harboured distinct plasmids and integron structures containing the bla(GIM-1) gene cassette. Interestingly, one of the two plasmids was able to replicate in Pseudomonas aeruginosa, demonstrating its broad host range. Conclusions This is the first identification in E. Cloacae of the bla(GIM-1) gene, which is responsible for reduced susceptibility to carbapenems. We showed that this gene, previously identified in P. aeruginosa, was located in a different genetic background in E. Cloacae. The bla(GIM-1) gene might spread quite efficiently in Enterobacteriaceae and P. aeruginosa, as it is difficult to detect and in addition is located on conjugative plasmids.
Francois Guerin - One of the best experts on this subject based on the ideXlab platform.
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cluster dependent colistin hetero resistance in Enterobacter Cloacae complex
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Francois Guerin, Christophe Isnard, Clara Sinel, Philippe Morand, Anne Dhalluin, Vincent Cattoir, Jeanchristophe GiardAbstract: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.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.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.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.
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cluster dependent colistin hetero resistance in Enterobacter Cloacae complex
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Francois Guerin, Christophe Isnard, Clara Sinel, Philippe Morand, Anne Dhalluin, Vincent Cattoir, Jeanchristophe GiardAbstract: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.