Analysis of the networks controlling the antimicrobial-peptide-dependent induction of Klebsiella pneumoniae virulence factors.

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dc.contributor.author Llobet, Enrique
dc.contributor.author Campos, Miguel A.
dc.contributor.author Giménez, Paloma
dc.contributor.author Moranta Mesquida, David
dc.contributor.author Bengoechea, José A.
dc.date.accessioned 2018-09-14T11:37:01Z
dc.identifier.uri http://hdl.handle.net/11201/147428
dc.description.abstract [eng] Antimicrobial peptides (APs) impose a threat to the survival of pathogens, and it is reasonable to postulate that bacteria have developed strategies to counteract them. Polymyxins are becoming the last resort to treat infections caused by multidrug-resistant Gram-negative bacteria and, similar to APs, they interact with the anionic lipopolysaccharide. Given that polymyxins and APs share the initial target, it is possible that bacterial defense mechanisms against polymyxins will be also effective against host APs. We sought to determine whether exposure to polymyxin will increase Klebsiella pneumoniae resistance to host APs. Indeed, exposure of K. pneumoniae to polymyxin induces cross-resistance not only to polymyxin itself but also to APs present in the airways. Polymyxin treatment upregulates the expression of the capsule polysaccharide operon and the loci required to modify the lipid A with aminoarabinose and palmitate with a concomitant increase in capsule and lipid A species containing such modifications. Moreover, these surface changes contribute to APs resistance and also to polymyxin-induced cross-resistance to APs. Bacterial loads of lipid A mutants in trachea and lungs of intranasally infected mice were lower than those of wild-type strain. PhoPQ, PmrAB, and the Rcs system govern polymyxin-induced transcriptional changes, and there is a cross talk between PhoPQ and the Rcs system. Our findings support the notion that Klebsiella activates a defense program against APs that is controlled by three signaling systems. Therapeutic strategies directed to prevent the activation of this program could be a new approach worth exploring to facilitate the clearance of the pathogen from the airways.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a: https://doi.org/10.1128/IAI.05226-11
dc.relation.ispartof Infection and Immunity, 2011, vol. 79, num. 9, p. 3718-3732
dc.rights (c) American Society for Microbiology, 2011
dc.subject.classification 579 - Microbiologia
dc.subject.other 579 - Microbiology
dc.title Analysis of the networks controlling the antimicrobial-peptide-dependent induction of Klebsiella pneumoniae virulence factors.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion
dc.date.updated 2018-09-14T11:37:01Z
dc.date.embargoEndDate info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.identifier.doi https://doi.org/10.1128/IAI.05226-11


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