Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis

Bacterial adaptation to antiseptic selective pressure might be associated with decreased susceptibility to antibiotics. In Gram-negative bacteria, some correlations between reduced susceptibility to chlorhexidine (CHX) and polymyxins have been recently evidenced in <i>Klebsiella pneumoniae<...

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Main Authors: Mathilde Lescat, Mélanie Magnan, Sonia Kenmoe, Patrice Nordmann, Laurent Poirel
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/11/1/50
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author Mathilde Lescat
Mélanie Magnan
Sonia Kenmoe
Patrice Nordmann
Laurent Poirel
author_facet Mathilde Lescat
Mélanie Magnan
Sonia Kenmoe
Patrice Nordmann
Laurent Poirel
author_sort Mathilde Lescat
collection DOAJ
description Bacterial adaptation to antiseptic selective pressure might be associated with decreased susceptibility to antibiotics. In Gram-negative bacteria, some correlations between reduced susceptibility to chlorhexidine (CHX) and polymyxins have been recently evidenced in <i>Klebsiella pneumoniae</i>. In the present study, four isolates belonging to distinct enterobacterial species, namely <i>K. pneumoniae</i>, <i>Escherichia coli</i>, <i>Klebsiella oxytoca</i> and <i>Enterobacter cloacae</i>, were submitted to in-vitro selective adaptation to two antiseptics, namely CHX and octenidine (OCT), and to the antibiotic colistin (COL). Using COL as selective agent, mutants showing high MICs for that molecule were recovered for <i>E. cloacae</i>, <i>K. pneumoniae</i> and <i>K. oxytoca</i>, exhibiting a moderate decreased susceptibility to CHX, whereas OCT susceptibility remained unchanged. Using CHX as selective agent, mutants with high MICs for that molecule were recovered for all four species, with a cross-resistance observed for COL, while OCT susceptibility remained unaffected. Finally, selection of mutants using OCT as selective molecule allowed recovery of <i>K. pneumoniae</i>, <i>K. oxytoca</i> and <i>E. cloacae</i> strains showing only slightly increased MICs for that molecule, without any cross-elevated MICs for the two other molecules tested. No <i>E. coli</i> mutant with reduced susceptibility to OCT could be obtained. It was therefore demonstrated that in-vitro mutants with decreased susceptibility to CHX and COL may be selected in <i>E. coli</i>, <i>K. pneumoniae</i>, <i>K. oxytoca</i> and <i>E. cloacae</i>, showing cross-decreased susceptibility to COL and CHX, but no significant impact on OCT efficacy. On the other hand, mutants were difficult to obtain with OCT, being obtained for <i>K. pneumoniae</i> and <i>E. cloacae</i> only, showing only very limited decreased susceptibility in those cases, and with no cross effect on other molecules. Whole genome sequencing enabled deciphering of the molecular basis of adaptation of these isolates under the respective selective pressures, with efflux pumps or lipopolysaccharide biosynthesis being the main mechanisms of adaptation.
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spelling doaj.art-b2c9a0c7d48e44dc9608fda39846cc602023-11-23T12:43:50ZengMDPI AGAntibiotics2079-63822021-12-011115010.3390/antibiotics11010050Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic AnalysisMathilde Lescat0Mélanie Magnan1Sonia Kenmoe2Patrice Nordmann3Laurent Poirel4Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandUniversité Sorbonne Paris Nord, 93000 Bobigny, FranceAP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, 93000 Bobigny, FranceEmerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandEmerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandBacterial adaptation to antiseptic selective pressure might be associated with decreased susceptibility to antibiotics. In Gram-negative bacteria, some correlations between reduced susceptibility to chlorhexidine (CHX) and polymyxins have been recently evidenced in <i>Klebsiella pneumoniae</i>. In the present study, four isolates belonging to distinct enterobacterial species, namely <i>K. pneumoniae</i>, <i>Escherichia coli</i>, <i>Klebsiella oxytoca</i> and <i>Enterobacter cloacae</i>, were submitted to in-vitro selective adaptation to two antiseptics, namely CHX and octenidine (OCT), and to the antibiotic colistin (COL). Using COL as selective agent, mutants showing high MICs for that molecule were recovered for <i>E. cloacae</i>, <i>K. pneumoniae</i> and <i>K. oxytoca</i>, exhibiting a moderate decreased susceptibility to CHX, whereas OCT susceptibility remained unchanged. Using CHX as selective agent, mutants with high MICs for that molecule were recovered for all four species, with a cross-resistance observed for COL, while OCT susceptibility remained unaffected. Finally, selection of mutants using OCT as selective molecule allowed recovery of <i>K. pneumoniae</i>, <i>K. oxytoca</i> and <i>E. cloacae</i> strains showing only slightly increased MICs for that molecule, without any cross-elevated MICs for the two other molecules tested. No <i>E. coli</i> mutant with reduced susceptibility to OCT could be obtained. It was therefore demonstrated that in-vitro mutants with decreased susceptibility to CHX and COL may be selected in <i>E. coli</i>, <i>K. pneumoniae</i>, <i>K. oxytoca</i> and <i>E. cloacae</i>, showing cross-decreased susceptibility to COL and CHX, but no significant impact on OCT efficacy. On the other hand, mutants were difficult to obtain with OCT, being obtained for <i>K. pneumoniae</i> and <i>E. cloacae</i> only, showing only very limited decreased susceptibility in those cases, and with no cross effect on other molecules. Whole genome sequencing enabled deciphering of the molecular basis of adaptation of these isolates under the respective selective pressures, with efflux pumps or lipopolysaccharide biosynthesis being the main mechanisms of adaptation.https://www.mdpi.com/2079-6382/11/1/50colistinresistancechlorhexidineoctenidine<i>Enterobacterales</i>
spellingShingle Mathilde Lescat
Mélanie Magnan
Sonia Kenmoe
Patrice Nordmann
Laurent Poirel
Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
Antibiotics
colistin
resistance
chlorhexidine
octenidine
<i>Enterobacterales</i>
title Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
title_full Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
title_fullStr Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
title_full_unstemmed Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
title_short Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
title_sort co lateral effect of octenidine chlorhexidine and colistin selective pressures on four enterobacterial species a comparative genomic analysis
topic colistin
resistance
chlorhexidine
octenidine
<i>Enterobacterales</i>
url https://www.mdpi.com/2079-6382/11/1/50
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