Affiliation:
1. Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597
Abstract
ABSTRACT
BpeAB-OprB is a multidrug efflux pump of the bacterial pathogen
Burkholderia pseudomallei
and is responsible for conferring antimicrobial resistance to aminoglycosides and macrolides. Expression of
bpeAB-oprB
is inducible by its substrate erythromycin and upon entry into stationary phase. BpeR, a member of the TetR family, functions as a repressor of the
bpeAB-oprB
operon.
bpeR
expression was similarly induced at stationary phase but lagged behind the induction of
bpeAB-oprB
expression. The induction of
bpeAB-oprB
expression could be advanced to the early exponential phase by exogenous addition of the
B. pseudomallei
autoinducers
N
-octanoyl-homoserine lactone (C8HSL) and
N
-decanoyl-homoserine lactone (C10HSL), suggesting that the
bpeAB-oprB
operon may be quorum regulated. On the other hand, acyl-homoserine lactone (acyl-HSL) production was undetectable in the
bpeAB
-null mutant and strains which overexpress
bpeR
. The failure of these strains to produce acyl-HSLs seemed to be at the level of synthesis of acyl-HSLs, as growth-phase-dependent expression of the autoinducer synthase BpsI was abolished in the
bpeAB
-null mutant.
bpsI
expression remained growth phase dependent in the
bpeR
mutant which had functional BpeAB-OprB. BpeAB-OprB function is likewise necessary for optimal production of quorum-sensing-controlled virulence factors such as siderophore and phospholipase C and for biofilm formation. Cell invasion and cytotoxicity towards human lung epithelial (A549) and human macrophage (THP-1) cells were also significantly attenuated in both the
bpeAB
mutant and
bpeR-
overexpressing strains, thus suggesting the possibility of attenuating
B. pseudomallei
virulence using inhibitors of the BpeAB-OprB efflux pump.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
107 articles.
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