Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.

Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, bacterial polysaccharides and proteins, which are up to 1000-fold more antibiotic resistant than planktonic cultures. To date, extracellular DNA has been shown to function as a structural support t...

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Autores principales:	Heidi Mulcahy, Laetitia Charron-Mazenod, Shawn Lewenza
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7bd227505f904b609fe516d462bf6e5d
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spelling	oai:doaj.org-article:7bd227505f904b609fe516d462bf6e5d2021-11-25T05:47:26ZExtracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.1553-73661553-737410.1371/journal.ppat.1000213https://doaj.org/article/7bd227505f904b609fe516d462bf6e5d2008-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19023416/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, bacterial polysaccharides and proteins, which are up to 1000-fold more antibiotic resistant than planktonic cultures. To date, extracellular DNA has been shown to function as a structural support to maintain Pseudomonas aeruginosa biofilm architecture. Here we show that DNA is a multifaceted component of P. aeruginosa biofilms. At physiologically relevant concentrations, extracellular DNA has antimicrobial activity, causing cell lysis by chelating cations that stabilize lipopolysaccharide (LPS) and the outer membrane (OM). DNA-mediated killing occurred within minutes, as a result of perturbation of both the outer and inner membrane (IM) and the release of cytoplasmic contents, including genomic DNA. Sub-inhibitory concentrations of DNA created a cation-limited environment that resulted in induction of the PhoPQ- and PmrAB-regulated cationic antimicrobial peptide resistance operon PA3552-PA3559 in P. aeruginosa. Furthermore, DNA-induced expression of this operon resulted in up to 2560-fold increased resistance to cationic antimicrobial peptides and 640-fold increased resistance to aminoglycosides, but had no effect on beta-lactam and fluoroquinolone resistance. Thus, the presence of extracellular DNA in the biofilm matrix contributes to cation gradients, genomic DNA release and inducible antibiotic resistance. DNA-rich environments, including biofilms and other infection sites like the CF lung, are likely the in vivo environments where extracellular pathogens such as P. aeruginosa encounter cation limitation.Heidi MulcahyLaetitia Charron-MazenodShawn LewenzaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 11, p e1000213 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Heidi Mulcahy Laetitia Charron-Mazenod Shawn Lewenza Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.
description	Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, bacterial polysaccharides and proteins, which are up to 1000-fold more antibiotic resistant than planktonic cultures. To date, extracellular DNA has been shown to function as a structural support to maintain Pseudomonas aeruginosa biofilm architecture. Here we show that DNA is a multifaceted component of P. aeruginosa biofilms. At physiologically relevant concentrations, extracellular DNA has antimicrobial activity, causing cell lysis by chelating cations that stabilize lipopolysaccharide (LPS) and the outer membrane (OM). DNA-mediated killing occurred within minutes, as a result of perturbation of both the outer and inner membrane (IM) and the release of cytoplasmic contents, including genomic DNA. Sub-inhibitory concentrations of DNA created a cation-limited environment that resulted in induction of the PhoPQ- and PmrAB-regulated cationic antimicrobial peptide resistance operon PA3552-PA3559 in P. aeruginosa. Furthermore, DNA-induced expression of this operon resulted in up to 2560-fold increased resistance to cationic antimicrobial peptides and 640-fold increased resistance to aminoglycosides, but had no effect on beta-lactam and fluoroquinolone resistance. Thus, the presence of extracellular DNA in the biofilm matrix contributes to cation gradients, genomic DNA release and inducible antibiotic resistance. DNA-rich environments, including biofilms and other infection sites like the CF lung, are likely the in vivo environments where extracellular pathogens such as P. aeruginosa encounter cation limitation.
format	article
author	Heidi Mulcahy Laetitia Charron-Mazenod Shawn Lewenza
author_facet	Heidi Mulcahy Laetitia Charron-Mazenod Shawn Lewenza
author_sort	Heidi Mulcahy
title	Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.
title_short	Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.
title_full	Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.
title_fullStr	Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.
title_full_unstemmed	Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.
title_sort	extracellular dna chelates cations and induces antibiotic resistance in pseudomonas aeruginosa biofilms.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/7bd227505f904b609fe516d462bf6e5d
work_keys_str_mv	AT heidimulcahy extracellulardnachelatescationsandinducesantibioticresistanceinpseudomonasaeruginosabiofilms AT laetitiacharronmazenod extracellulardnachelatescationsandinducesantibioticresistanceinpseudomonasaeruginosabiofilms AT shawnlewenza extracellulardnachelatescationsandinducesantibioticresistanceinpseudomonasaeruginosabiofilms
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Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.

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