Back to Search Start Over

Polymyxin Resistance of Pseudomonas aeruginosa phoQMutants Is Dependent on Additional Two-Component Regulatory Systems

Authors :
Gutu, Alina D.
Sgambati, Nicole
Strasbourger, Pnina
Brannon, Mark K.
Jacobs, Michael A.
Haugen, Eric
Kaul, Rajinder K.
Johansen, Helle Krogh
Høiby, Niels
Moskowitz, Samuel M.
Source :
Antimicrobial Agents and Chemotherapy; March 2013, Vol. 57 Issue: 5 p2204-2215, 12p
Publication Year :
2013

Abstract

ABSTRACTPseudomonas aeruginosacan develop resistance to polymyxin as a consequence of mutations in the PhoPQ regulatory system, mediated by covalent lipid A modification. Transposon mutagenesis of a polymyxin-resistant phoQmutant defined 41 novel loci required for resistance, including two regulatory systems, ColRS and CprRS. Deletion of the colRSgenes, individually or in tandem, abrogated the polymyxin resistance of a ΔphoQmutant, as did individual or tandem deletion of cprRS. Individual deletion of colRor colSin a ΔphoQmutant also suppressed 4-amino-l-arabinose addition to lipid A, consistent with the known role of this modification in polymyxin resistance. Surprisingly, tandem deletion of colRSor cprRSin the ΔphoQmutant or individual deletion of cprRor cprSfailed to suppress 4-amino-l-arabinose addition to lipid A, indicating that this modification alone is not sufficient for PhoPQ-mediated polymyxin resistance in P. aeruginosa. Episomal expression of colRSor cprRSin tandem or of cprRindividually complemented the Pm resistance phenotype in the ΔphoQmutant, while episomal expression of colR, colS, or cprSindividually did not. Highly polymyxin-resistant phoQmutants of P. aeruginosaisolated from polymyxin-treated cystic fibrosis patients harbored mutant alleles of colRSand cprS; when expressed in a ΔphoQbackground, these mutant alleles enhanced polymyxin resistance. These results define ColRS and CprRS as two-component systems regulating polymyxin resistance in P. aeruginosa, indicate that addition of 4-amino-l-arabinose to lipid A is not the only PhoPQ-regulated biochemical mechanism required for resistance, and demonstrate that colRSand cprSmutations can contribute to high-level clinical resistance.

Details

Language :
English
ISSN :
00664804 and 10986596
Volume :
57
Issue :
5
Database :
Supplemental Index
Journal :
Antimicrobial Agents and Chemotherapy
Publication Type :
Periodical
Accession number :
ejs30120781
Full Text :
https://doi.org/10.1128/AAC.02353-12