scholarly journals Control of Quorum Sensing by a Burkholderia pseudomallei Multidrug Efflux Pump

2007 ◽  
Vol 189 (11) ◽  
pp. 4320-4324 ◽  
Author(s):  
Ying Ying Chan ◽  
Hao Sheng Bian ◽  
Theresa May Chin Tan ◽  
Margrith E. Mattmann ◽  
Grant D. Geske ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Pseudomallei ◽  
Efflux Pump ◽  
Homoserine Lactone ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Homoserine Lactones ◽  
Extracellular Secretion ◽  
Sensing Systems ◽  
Acyl Homoserine Lactones

ABSTRACT The Burkholderia pseudomallei KHW quorum-sensing systems produced N-octanoyl-homoserine lactone, N-decanoyl-homoserine lactone, N-(3-hydroxy)-octanoyl-homoserine lactone, N-(3-hydroxy)-decanoyl-homoserine lactone, N-(3-oxo)-decanoyl-homoserine lactone, and N-(3-oxo)-tetradecanoyl-homoserine lactone. The extracellular secretion of these acyl-homoserine lactones is dependent absolutely on the function of the B. pseudomallei BpeAB-OprB efflux pump.

scholarly journals The BpeAB-OprB Efflux Pump of Burkholderia pseudomallei 1026b Does Not Play a Role in Quorum Sensing, Virulence Factor Production, or Extrusion of Aminoglycosides but Is a Broad-Spectrum Drug Efflux System

2010 ◽  
Vol 54 (8) ◽  
pp. 3113-3120 ◽  
Author(s):  
Takehiko Mima ◽  
Herbert P. Schweizer
Keyword(s):  
Quorum Sensing ◽  
Virulence Factor ◽  
Burkholderia Pseudomallei ◽  
Efflux Pump ◽  
Homoserine Lactone ◽  
Genetically Engineered ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Aminoglycoside Resistance

ABSTRACT Most Burkholderia pseudomallei strains are intrinsically aminoglycoside resistant, mainly due to AmrAB-OprA-mediated efflux. Rare naturally occurring or genetically engineered mutants lacking this pump are aminoglycoside susceptible despite the fact that they also encode and express BpeAB-OprB, which was reported to mediate efflux of aminoglycosides in the Singapore strain KHW. To reassess the role of BpeAB-OprB in B. pseudomallei aminoglycoside resistance, we used mutants overexpressing or lacking this pump in either AmrAB-OprA-proficient or -deficient strain 1026b backgrounds. Our data show that BpeAB-OprB does not mediate efflux of aminoglycosides but is a multidrug efflux system which extrudes macrolides, fluoroquinolones, tetracyclines, acriflavine, and, to a lesser extent, chloramphenicol. Phylogenetically, BpeAB-OprB is closely related to Pseudomonas aeruginosa MexAB-OprM, which has a similar substrate spectrum. AmrAB-OprA is most closely related to MexXY, the only P. aeruginosa efflux pump known to extrude aminoglycosides. Since BpeAB-OprB in strain KHW was also implicated in playing a major role in export of acylated homoserine lactone (AHL) quorum-sensing molecules and in expression of diverse virulence factors, we explored whether this was also true in the strain 1026b background. The results showed that BpeAB-OprB was not required for AHL export, and mutants lacking this efflux system exhibited normal swimming motility and siderophore production, which were severely impaired in KHW bpeAB-oprB mutants. Biofilm formation was impaired in 1026b Δ(amrRAB-oprA) and Δ(amrRAB-oprA) Δ(bpeAB-oprB) mutants. At present, we do not know why our BpeAB-OprB susceptibility and virulence factor expression results with 1026b and its derivatives are different from those previously published for Singapore strain KHW.

scholarly journals The Burkholderia pseudomallei BpeAB-OprB Efflux Pump: Expression and Impact on Quorum Sensing and Virulence

2005 ◽  
Vol 187 (14) ◽  
pp. 4707-4719 ◽  
Author(s):  
Ying Ying Chan ◽  
Kim Lee Chua
Keyword(s):  
Quorum Sensing ◽  
Stationary Phase ◽  
Growth Phase ◽  
Burkholderia Pseudomallei ◽  
Efflux Pump ◽  
Bacterial Pathogen ◽  
Homoserine Lactone ◽  
Human Macrophage ◽  
Null Mutant ◽  
Multidrug Efflux Pump

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.

scholarly journals Control of Biofilm Formation in Healthcare: Recent Advances Exploiting Quorum-Sensing Interference Strategies and Multidrug Efflux Pump Inhibitors

Materials ◽  
2018 ◽  
Vol 11 (9) ◽  
pp. 1676 ◽  
Author(s):  
Bindu Subhadra ◽  
Dong Kim ◽  
Kyungho Woo ◽  
Surya Surendran ◽  
Chul Choi
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Financial Burden ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Persistent Infections ◽  
Healthcare Settings ◽  
Recent Advances ◽  
Multidrug Efflux Pumps

Biofilm formation in healthcare is an issue of considerable concern, as it results in increased morbidity and mortality, imposing a significant financial burden on the healthcare system. Biofilms are highly resistant to conventional antimicrobial therapies and lead to persistent infections. Hence, there is a high demand for novel strategies other than conventional antibiotic therapies to control biofilm-based infections. There are two approaches which have been employed so far to control biofilm formation in healthcare settings: one is the development of biofilm inhibitors based on the understanding of the molecular mechanism of biofilm formation, and the other is to modify the biomaterials which are used in medical devices to prevent biofilm formation. This review will focus on the recent advances in anti-biofilm approaches by interrupting the quorum-sensing cellular communication system and the multidrug efflux pumps which play an important role in biofilm formation. Research efforts directed towards these promising strategies could eventually lead to the development of better anti-biofilm therapies than the conventional treatments.

scholarly journals Burkholderia pseudomallei, B. thailandensis, and B. ambifaria Produce 4-Hydroxy-2-Alkylquinoline Analogues with a Methyl Group at the 3 Position That Is Required for Quorum-Sensing Regulation

2008 ◽  
Vol 190 (15) ◽  
pp. 5339-5352 ◽  
Author(s):  
Ludovic Vial ◽  
François Lépine ◽  
Sylvain Milot ◽  
Marie-Christine Groleau ◽  
Valérie Dekimpe ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
Burkholderia Pseudomallei ◽  
Alkyl Chain ◽  
Quinoline Ring ◽  
Liquid Chromatography Mass Spectrometry ◽  
Methyl Group ◽  
Homoserine Lactones ◽  
Acyl Homoserine Lactones ◽  
Oxide Group

ABSTRACT 4-Hydroxy-2-alkylquinolines (HAQs), especially 3,4-dihydroxy-2-heptylquinoline (Pseudomonas quinolone signal) and its precursor, 4-hydroxy-2-heptylquinoline, are attracting much attention, mainly because of their role as signaling molecules in Pseudomonas aeruginosa. The pqsABCDE operon is centrally involved in their biosynthesis. The presence of a homologous operon in Burkholderia pseudomallei and B. thailandensis was recently reported. Thus, we have investigated the abilities of 11 Burkholderia species to produce HAQ-like molecules by liquid chromatography/mass spectrometry. We have identified 29 different HAQ derivatives produced by the only three Burkholderia species where a pqsABCDE homologue was found among available sequenced Burkholderia species genomes, including B. ambifaria, a member of the Burkholderia cepacia complex. In contrast with those of P. aeruginosa, Burkholderia HAQs typically bear a methyl group, hence their designation as 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs). We identified three families of HMAQs with a saturated or unsaturated alkyl chain at the 2′ position, in contrast with the 1′ position of P. aeruginosa, including one with an N-oxide group. Furthermore, the operon in these species contains two more genes downstream of the pqsE homologue, resulting in the hmqABCDEFG operon. While the inactivation of hmqA inhibits the production of HMAQs, the methylation of the quinoline ring requires a putative methyltransferase encoded by hmqG. Interestingly, hmqA or hmqG mutations increase the production of acyl homoserine lactones and, consequently, phenotypes under the control of quorum sensing in B. ambifaria: antifungal activity, siderophore production, and proteolytic activity. These results indicate that only HAQs bearing a methyl group (HMAQs) are involved in quorum-sensing regulation.

scholarly journals Overexpression of the MexEF-OprN Multidrug Efflux System Affects Cell-to-Cell Signaling in Pseudomonas aeruginosa

2001 ◽  
Vol 183 (18) ◽  
pp. 5213-5222 ◽  
Author(s):  
Thilo Köhler ◽  
Christian van Delden ◽  
Lasta Kocjancic Curty ◽  
Mehri Michea Hamzehpour ◽  
Jean-Claude Pechere
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Homoserine Lactone ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Sensing Systems ◽  
In The Wild ◽  
Type Mutant ◽  
Regulator Genes

ABSTRACT Intrinsic and acquired antibiotic resistance of the nosocomial pathogen Pseudomonas aeruginosa is mediated mainly by the expression of several efflux pumps of broad substrate specificity. Here we report that nfxC type mutants, overexpressing the MexEF-OprN efflux system, produce lower levels of extracellular virulence factors than the susceptible wild type. These include pyocyanin, elastase, and rhamnolipids, three factors controlled by the las and rhl quorum-sensing systems of P. aeruginosa. In agreement with these observations are the decreased transcription of the elastase genelasB and the rhamnosyltransferase genesrhlAB measured in nfxC type mutants. Expression of the lasR and rhlR regulator genes was not affected in the nfxC type mutant. In contrast, transcription of the C4-homoserine lactone (C4-HSL) autoinducer synthase gene rhlI was reduced by 50% in the nfxC type mutant relative to that in the wild type. This correlates with a similar decrease in C4-HSL levels detected in supernatants of the nfxC type mutant. Transcription of an rhlAB-lacZ fusion could be partially restored by the addition of synthetic C4-HSL andPseudomonas quinolone signal (PQS). It is proposed that the MexEF-OprN efflux pump affects intracellular PQS levels.

scholarly journals raiIR Genes Are Part of a Quorum-Sensing Network Controlled by cinI and cinR in Rhizobium leguminosarum

2002 ◽  
Vol 184 (6) ◽  
pp. 1597-1606 ◽  
Author(s):  
F. Wisniewski-Dyé ◽  
J. Jones ◽  
S. R. Chhabra ◽  
J. A. Downie
Keyword(s):  
Quorum Sensing ◽  
Rhizobium Leguminosarum ◽  
Homoserine Lactone ◽  
Major Product ◽  
Homoserine Lactones ◽  
Indigenous Plasmid ◽  
Sensing Systems ◽  
Regulatory Systems ◽  
Normal Expression ◽  
Low Levels

ABSTRACT Analysis of N-acyl-l-homoserine lactones (AHLs) produced by Rhizobium leguminosarum bv. viciae indicated that there may be a network of quorum-sensing regulatory systems producing multiple AHLs in this species. Using a strain lacking a symbiosis plasmid, which carries some of the quorum-sensing genes, we isolated mutations in two genes (raiI and raiR) that are required for production of AHLs. The raiIR genes are located adjacent to dad genes (involved in d-alanine catabolism) on a large indigenous plasmid. RaiR is predicted to be a typical LuxR-type quorum-sensing regulator and is required for raiI expression. The raiR gene was expressed at a low level, possibly from a constitutive promoter, and its expression was increased under the influence of the upstream raiI promoter. Using gene fusions and analysis of AHLs produced, we showed that expression of raiI is strongly reduced in strains carrying mutations in cinI or cinR, genes which determine a higher-level quorum-sensing system that is required for normal expression of raiIR. The product of CinI, N-(3-hydroxy-7-cis tetradecenoyl) homoserine lactone, can induce raiR-dependent raiI expression, although higher levels of expression are induced by other AHLs. Expression of raiI in a strain of Agrobacterium that makes no AHLs resulted in the identification of N-(3-hydroxyoctanoyl)-l-homoserine lactone (3OH,C8-HSL) as the major product of RaiI, although other AHLs that comigrate with N-hexanoyl-, N-heptanoyl-, and N-octanoyl-homoserine lactones were also made at low levels. The raiI gene was strongly induced by 3OH,C8-HSL (the product of RaiI) but could also be induced by other AHLs, suggesting that the raiI promoter can be activated by other quorum-sensing systems within a network of regulation which also involves AHLs determined by genes on the symbiotic plasmid. Thus, the raiIR and cinIR genes are part of a complex regulatory network that influences AHL biosynthesis in R. leguminosarum.

scholarly journals N-Octanoylhomoserine lactone signalling mediated by the BpsI–BpsR quorum sensing system plays a major role in biofilm formation of Burkholderia pseudomallei

Microbiology ◽  
2011 ◽  
Vol 157 (4) ◽  
pp. 1176-1186 ◽  
Author(s):  
Akshamal Mihiranga Gamage ◽  
Guanghou Shui ◽  
Markus R. Wenk ◽  
Kim Lee Chua
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Burkholderia Pseudomallei ◽  
Homoserine Lactone ◽  
Tandem Ms ◽  
Wild Type ◽  
Acylhomoserine Lactone ◽  
Sensing System ◽  
Sensing Systems ◽  
Quorum Sensing System

The genome of Burkholderia pseudomallei encodes three acylhomoserine lactone (AHL) quorum sensing systems, each comprising an AHL synthase and a signal receptor/regulator. The BpsI–BpsR system produces N-octanoylhomoserine lactone (C8HL) and is positively auto-regulated by its AHL product. The products of the remaining two systems have not been identified. In this study, tandem MS was used to identify and quantify the AHL species produced by three clinical B. pseudomallei isolates – KHW, K96243 and H11 – three isogenic KHW mutants that each contain a null mutation in an AHL synthase gene, and recombinant Escherichia coli heterologously expressing each of the three B. pseudomallei AHL synthase genes. BpsI synthesized predominantly C8HL, which accounted for more than 95 % of the extracellular AHLs produced in stationary-phase KHW cultures. The major products of BpsI2 and BpsI3 were N-(3-hydroxy-octanoyl)homoserine lactone (OHC8HL) and N-(3-hydroxy-decanoyl)homoserine lactone, respectively, and their corresponding transcriptional regulators, BpsR2 and BpsR3, were capable of driving reporter gene expression in the presence of these cognate lactones. Formation of biofilm by B. pseudomallei KHW was severely impaired in mutants lacking either BpsI or BpsR but could be restored to near wild-type levels by exogenous C8HL. BpsI2 was not required, and BpsI3 was partially required for biofilm formation. Unlike the bpsI mutant, biofilm formation in the bpsI3 mutant could not be restored to wild-type levels in the presence of OHC8HL, the product of BpsI3. C8HL and OHC8HL had opposite effects on biofilm formation; exogenous C8HL enhanced biofilm formation in both the bpsI3 mutant and wild-type KHW while exogenous OHC8HL suppressed the formation of biofilm in the same strains. We propose that exogenous OHC8HL antagonizes biofilm formation in B. pseudomallei, possibly by competing with endogenous C8HL for binding to BpsR.

scholarly journals Control of the AcrAB multidrug efflux pump by quorum-sensing regulator SdiA

2002 ◽  
Vol 43 (3) ◽  
pp. 677-685 ◽  
Author(s):  
Sonia Rahmati ◽  
Shirley Yang ◽  
Amy L. Davidson ◽  
E. Lynn Zechiedrich
Keyword(s):  
Quorum Sensing ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump

scholarly journals Long-Chain Acyl-Homoserine Lactone Quorum-Sensing Regulation of Rhodobacter capsulatus Gene Transfer Agent Production

2002 ◽  
Vol 184 (23) ◽  
pp. 6515-6521 ◽  
Author(s):  
Amy L. Schaefer ◽  
Terumi A. Taylor ◽  
J. Thomas Beatty ◽  
E. P. Greenberg
Keyword(s):  
Gene Transfer ◽  
Quorum Sensing ◽  
Rhodobacter Capsulatus ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Homoserine Lactones ◽  
Acyl Homoserine Lactones ◽  
Chain Acyl ◽  
Gene Transfer Agent ◽  
Long Chain

ABSTRACT Many proteobacteria use acyl-homoserine lactones as quorum-sensing signals. Traditionally, biological detection systems have been used to identify bacteria that produce acyl-homoserine lactones, although the specificities of these detection systems can limit discovery. We used a sensitive approach that did not require a bioassay to detect production of long-acyl-chain homoserine lactone production by Rhodobacter capsulatus and Paracoccus denitrificans. These long-chain acyl-homoserine lactones are not readily detected by standard bioassays. The most abundant acyl-homoserine lactone was N-hexadecanoyl-homoserine lactone. The long-chain acyl-homoserine lactones were concentrated in cells but were also found in the culture fluid. An R. capsulatus gene responsible for long-chain acyl-homoserine lactone synthesis was identified. A mutation in this gene, which we named gtaI, resulted in decreased production of the R. capsulatus gene transfer agent, and gene transfer agent production was restored by exogenous addition of N-hexadecanoyl-homoserine lactone. Thus, long-chain acyl-homoserine lactones serve as quorum-sensing signals to enhance genetic exchange in R. capsulatus.

scholarly journals Candida albicans Zn Cluster Transcription Factors Tac1 and Znc1 Are Activated by Farnesol To Upregulate a Transcriptional Program Including the Multidrug Efflux Pump CDR1

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Zhongle Liu ◽  
John M. Rossi ◽  
Lawrence C. Myers
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Quorum Sensing ◽  
Efflux Pump ◽  
Close Relative ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Content Type ◽  
Dna Binding Specificity ◽  
Hyphal Formation

ABSTRACT Farnesol, a quorum-sensing molecule, inhibits Candida albicans hyphal formation, affects its biofilm formation and dispersal, and impacts its stress response. Several aspects of farnesol's mechanism of action remain incompletely uncharacterized. Among these are a thorough accounting of the cellular receptors and transporters for farnesol. This work suggests these processes are linked through the Zn cluster transcription factors Tac1 and Znc1 and their induction of the multidrug efflux pump Cdr1. Specifically, we have demonstrated that Tac1 and Znc1 are functionally activated by farnesol through a mechanism that mimics other means of hyperactivation of Zn cluster transcription factors. This is consistent with our observation that many genes acutely induced by farnesol are dependent on TAC1, ZNC1, or both. A related molecule, 1-dodecanol, invokes a similar TAC1-ZNC1 response, while several other proposed C. albicans quorum-sensing molecules do not. Tac1 and Znc1 both bind to and upregulate the CDR1 promoter in response to farnesol. Differences in inducer and DNA binding specificity lead to Tac1 and Znc1 having overlapping, but nonidentical, regulons. Induction of genes by farnesol via Tac1 and Znc1 was inversely related to the level of CDR1 present in the cell, suggesting a model in which induction of CDR1 by Tac1 and Znc1 leads to an increase in farnesol efflux. Consistent with this premise, our results show that CDR1 expression, and its regulation by TAC1 and ZNC1, facilitates growth in the presence of high farnesol concentrations in C. albicans and in certain strains of its close relative, C. dubliniensis.

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