Lipopolysaccharide structure modulates cationic biocide susceptibility and crystalline biofilm formation in Proteus mirabilis

Publication type:
Journal article
Metadata:
Autoren
  • OE Clarke
  • H Pelling
  • V Bennett
  • T Matsumoto
  • GE Gregory
  • J Nzakizwanayo
  • AJ Slate
  • A Preston
  • M Laabei
  • LJ Bock
  • ME Wand
  • K Ikebukuro
  • S Gebhard
  • JM Sutton
  • BV Jones
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000971414800001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3389/fmicb.2023.1150625
eISSN
1664-302X
Externe Identifier
  • Clarivate Analytics Document Solution ID: D8UC5
  • PubMed Identifier: 37089543
Zeitschrift
FRONTIERS IN MICROBIOLOGY
Schlüsselwörter
  • Proteus mirabilis
  • biocide
  • biofilm
  • lipopolysaccharide
  • catheter associated urinary tract infection
  • biocide resistance
  • antimicrobials
  • AMR
Artikelnummer
ARTN 1150625
Datum der Veröffentlichung
2023
Status
Published
Titel
Lipopolysaccharide structure modulates cationic biocide susceptibility and crystalline biofilm formation in <i>Proteus mirabilis</i>
Sub types
  • Article
Ausgabe der Zeitschrift
14

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>Chlorhexidine (CHD) is a cationic biocide used ubiquitously in healthcare settings. <jats:italic>Proteus mirabilis</jats:italic>, an important pathogen of the catheterized urinary tract, and isolates of this species are often described as “resistant” to CHD-containing products used for catheter infection control. To identify the mechanisms underlying reduced CHD susceptibility in <jats:italic>P. mirabilis</jats:italic>, we subjected the CHD tolerant clinical isolate RS47 to random transposon mutagenesis and screened for mutants with reduced CHD minimum inhibitory concentrations (MICs). One mutant recovered from these screens (designated RS47-2) exhibited ~ 8-fold reduction in CHD MIC. Complete genome sequencing of RS47-2 showed a single mini-Tn<jats:italic>5</jats:italic> insert in the <jats:italic>waaC</jats:italic> gene involved in lipopolysaccharide (LPS) inner core biosynthesis. Phenotypic screening of RS47-2 revealed a significant increase in cell surface hydrophobicity and serum susceptibility compared to the wildtype, and confirmed defects in LPS production congruent with <jats:italic>waaC</jats:italic> inactivation. Disruption of <jats:italic>waaC</jats:italic> was also associated with increased susceptibility to a range of other cationic biocides but did not affect susceptibility to antibiotics tested. Complementation studies showed that repression of <jats:italic>smvA</jats:italic> efflux activity in RS47-2 further increased susceptibility to CHD and other cationic biocides, reducing CHD MICs to values comparable with the most CHD susceptible isolates characterized. The formation of crystalline biofilms and blockage of urethral catheters was also significantly attenuated in RS47-2. Taken together, these data show that aspects of LPS structure and upregulation of the <jats:italic>smvA</jats:italic> efflux system function in synergy to modulate susceptibility to CHD and other cationic biocides, and that LPS structure is also an important factor in <jats:italic>P. mirabilis</jats:italic> crystalline biofilm formation.</jats:p>
Autoren
  • OE Clarke
  • H Pelling
  • V Bennett
  • T Matsumoto
  • GE Gregory
  • J Nzakizwanayo
  • AJ Slate
  • A Preston
  • M Laabei
  • LJ Bock
  • ME Wand
  • K Ikebukuro
  • S Gebhard
  • JM Sutton
  • BV Jones
DOI
10.3389/fmicb.2023.1150625
eISSN
1664-302X
Zeitschrift
Frontiers in Microbiology
Online publication date
2023
Status
Published online
Herausgeber
Frontiers Media SA
Herausgeber URL
http://dx.doi.org/10.3389/fmicb.2023.1150625
Datum der Datenerfassung
2023
Titel
Lipopolysaccharide structure modulates cationic biocide susceptibility and crystalline biofilm formation in Proteus mirabilis
Ausgabe der Zeitschrift
14

Data source: Crossref

Abstract
Chlorhexidine (CHD) is a cationic biocide used ubiquitously in healthcare settings. <i>Proteus mirabilis</i>, an important pathogen of the catheterized urinary tract, and isolates of this species are often described as "resistant" to CHD-containing products used for catheter infection control. To identify the mechanisms underlying reduced CHD susceptibility in <i>P. mirabilis</i>, we subjected the CHD tolerant clinical isolate RS47 to random transposon mutagenesis and screened for mutants with reduced CHD minimum inhibitory concentrations (MICs). One mutant recovered from these screens (designated RS47-2) exhibited ~ 8-fold reduction in CHD MIC. Complete genome sequencing of RS47-2 showed a single mini-Tn<i>5</i> insert in the <i>waaC</i> gene involved in lipopolysaccharide (LPS) inner core biosynthesis. Phenotypic screening of RS47-2 revealed a significant increase in cell surface hydrophobicity and serum susceptibility compared to the wildtype, and confirmed defects in LPS production congruent with <i>waaC</i> inactivation. Disruption of <i>waaC</i> was also associated with increased susceptibility to a range of other cationic biocides but did not affect susceptibility to antibiotics tested. Complementation studies showed that repression of <i>smvA</i> efflux activity in RS47-2 further increased susceptibility to CHD and other cationic biocides, reducing CHD MICs to values comparable with the most CHD susceptible isolates characterized. The formation of crystalline biofilms and blockage of urethral catheters was also significantly attenuated in RS47-2. Taken together, these data show that aspects of LPS structure and upregulation of the <i>smvA</i> efflux system function in synergy to modulate susceptibility to CHD and other cationic biocides, and that LPS structure is also an important factor in <i>P. mirabilis</i> crystalline biofilm formation.
Addresses
  • Department of Life Sciences, University of Bath, Bath, United Kingdom.
Autoren
  • OE Clarke
  • H Pelling
  • V Bennett
  • T Matsumoto
  • GE Gregory
  • J Nzakizwanayo
  • AJ Slate
  • A Preston
  • M Laabei
  • LJ Bock
  • ME Wand
  • K Ikebukuro
  • S Gebhard
  • JM Sutton
  • BV Jones
DOI
10.3389/fmicb.2023.1150625
eISSN
1664-302X
Externe Identifier
  • PubMed Identifier: 37089543
  • PubMed Central ID: PMC10113676
Funding acknowledgements
  • The Dunhill Medical Trust: RPGF1906\171
  • Wellcome Trust: 206854/Z/17/Z
  • Wellcome Trust:
Open access
true
ISSN
1664-302X
Zeitschrift
Frontiers in microbiology
Sprache
eng
Medium
Electronic-eCollection
Online publication date
2023
Open access status
Open Access
Paginierung
1150625
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Lipopolysaccharide structure modulates cationic biocide susceptibility and crystalline biofilm formation in <i>Proteus mirabilis</i>.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
14

Files

https://www.frontiersin.org/articles/10.3389/fmicb.2023.1150625/pdf https://europepmc.org/articles/PMC10113676?pdf=render

Data source: Europe PubMed Central

Abstract
Chlorhexidine (CHD) is a cationic biocide used ubiquitously in healthcare settings. Proteus mirabilis, an important pathogen of the catheterized urinary tract, and isolates of this species are often described as "resistant" to CHD-containing products used for catheter infection control. To identify the mechanisms underlying reduced CHD susceptibility in P. mirabilis, we subjected the CHD tolerant clinical isolate RS47 to random transposon mutagenesis and screened for mutants with reduced CHD minimum inhibitory concentrations (MICs). One mutant recovered from these screens (designated RS47-2) exhibited ~ 8-fold reduction in CHD MIC. Complete genome sequencing of RS47-2 showed a single mini-Tn5 insert in the waaC gene involved in lipopolysaccharide (LPS) inner core biosynthesis. Phenotypic screening of RS47-2 revealed a significant increase in cell surface hydrophobicity and serum susceptibility compared to the wildtype, and confirmed defects in LPS production congruent with waaC inactivation. Disruption of waaC was also associated with increased susceptibility to a range of other cationic biocides but did not affect susceptibility to antibiotics tested. Complementation studies showed that repression of smvA efflux activity in RS47-2 further increased susceptibility to CHD and other cationic biocides, reducing CHD MICs to values comparable with the most CHD susceptible isolates characterized. The formation of crystalline biofilms and blockage of urethral catheters was also significantly attenuated in RS47-2. Taken together, these data show that aspects of LPS structure and upregulation of the smvA efflux system function in synergy to modulate susceptibility to CHD and other cationic biocides, and that LPS structure is also an important factor in P. mirabilis crystalline biofilm formation.
Date of acceptance
2023
Autoren
  • OE Clarke
  • H Pelling
  • V Bennett
  • T Matsumoto
  • GE Gregory
  • J Nzakizwanayo
  • AJ Slate
  • A Preston
  • M Laabei
  • LJ Bock
  • ME Wand
  • K Ikebukuro
  • S Gebhard
  • JM Sutton
  • BV Jones
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37089543
DOI
10.3389/fmicb.2023.1150625
Externe Identifier
  • PubMed Central ID: PMC10113676
Funding acknowledgements
  • Wellcome Trust:
ISSN
1664-302X
Zeitschrift
Front Microbiol
Schlüsselwörter
  • AMR
  • Proteus mirabilis
  • antimicrobials
  • biocide
  • biocide resistance
  • biofilm
  • catheter associated urinary tract infection
  • lipopolysaccharide
Sprache
eng
Country
Switzerland
Paginierung
1150625
Datum der Veröffentlichung
2023
Status
Published online
Titel
Lipopolysaccharide structure modulates cationic biocide susceptibility and crystalline biofilm formation in Proteus mirabilis.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
14

Data source: PubMed

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