Affiliation:
1. Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523-1682
2. Faculty of Health, Leeds Metropolitan University, Leeds LS1 3HE, United Kingdom
Abstract
ABSTRACT
Pseudomonas aeruginosa
achieves high-level (MIC > 1 mg/ml) triclosan resistance either by constitutive expression of MexAB-OprM, an efflux pump of the resistance nodulation cell division (RND) family, or expression of MexCD-OprJ, MexEF-OprN, and MexJK-OpmH in regulatory mutants. A triclosan-resistant target enzyme and perhaps other mechanisms probably act synergistically with efflux. To probe this notion, we exposed the susceptible Δ(
mexAB-oprM
) Δ(
mexCD-oprJ
) Δ(
mexEF-oprN
) Δ(
mexJK
) Δ(
mexXY
) strain PAO509 to increasing triclosan concentrations and derived a resistant strain, PAO509.5. This mutant overexpressed the PA0156-PA0157-PA0158 pump, which only effluxed triclosan, but not closely related compounds, antibiotics, and divalent cations, and was therefore renamed TriABC. Constitutive expression of the
triABC
operon was due to a single promoter-up mutation. Deletion of two adjacent genes,
pcaR
and
PA0159
, encoding transcriptional regulators had no effect on expression of this operon. TriABC is the only
P. aeruginosa
RND pump which contains two membrane fusion proteins, TriA and TriB, and both are required for efflux pump function. Probably owing to tight transcriptional coupling of the
triABC
genes, complementation of individual mutations was only partially achievable. Full complementation was only observed when a complete
triABC
operon was provided in
trans
, either in single or multiple copies. TriABC associated with OpmH, but not OprM, for assembly of a functional triclosan efflux pump. TriABC is the fifth RND pump in
P. aeruginosa
shown to efficiently efflux triclosan, supporting the notion that efflux is the primary mechanism responsible for this bacterium's high intrinsic and acquired triclosan resistance.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
121 articles.
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