10′(Z),13′(E)-Heptadecadienylhydroquinone Inhibits Swarming and Virulence Factors and Increases Polymyxin B Susceptibility in Proteus mirabilis

Ming-Che Liu, Shwu-Bin Lin, Hsiung-Fei Chien, Won-Bo Wang, Yu-Han Yuan, Po-Ren Hsueh, Shwu-Jen Liaw

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In this study, we demonstrated that 10′(Z), 13′(E)-heptadecadienylhydroquinone (HQ17-2), isolated from the lacquer tree, could decrease swarming motility and hemolysin activity but increase polymyxin B (PB) susceptibilityof Proteus mirabilis which is intrinsically highly-resistant to PB. The increased PB susceptibility induced by HQ17-2 was also observed in clinical isolates and biofilm-grown cells. HQ17-2 could inhibit swarming in the wild-type and rppA mutant but not in the rcsB mutant, indicating that HQ17-2 inhibits swarming through the RcsB-dependent pathway, a two-component signaling pathway negatively regulating swarming and virulence factor expression. The inhibition of hemolysin activity by HQ17-2 is also mediated through the RcsB-dependent pathway, because HQ17-2 could not inhibit hemolysin activity in the rcsB mutant. Moreover, the finding that HQ17-2 inhibits the expression of flhDC gene in the wild-type and rcsB-complemented strain but not in the rcsB mutant supports the notion. By contrast, HQ17-2 could increase PB susceptibility in the wild-type and rcsB mutant but not in the rppA mutant, indicating that HQ17-2 increases PB susceptibility through the RppA-dependent pathway, a signaling pathway positively regulating PB resistance. In addition, HQ17-2 could inhibit the promoter activities of rppA and pmrI, a gene positively regulated by RppA and involved in PB resistance, in the wild-type but not in the rppA mutant. The inhibition of rppA and pmrI expression caused lipopolysaccharide purified from HQ17-2-treated cells to have higher affinity for PB. Altogether, this study uncovers new biological effects of HQ17-2 and provides evidence for the potential of HQ17-2 in clinical applications. © 2012 Liu et al.
Original languageEnglish
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • 10',13' heptadecadienylhydroquinone
  • ampicillin
  • bacterial protein
  • ciprofloxacin
  • gentamicin
  • hemolysin
  • hydroquinone derivative
  • kanamycin
  • lipopolysaccharide
  • polymyxin B
  • protein rcsB
  • protein rppA
  • streptomycin
  • tetracycline
  • unclassified drug
  • virulence factor
  • 10'(Z),13'(E) heptadecadienylhydroquinone
  • 10'(Z),13'(E)-heptadecadienylhydroquinone
  • acyltransferase
  • antiinfective agent
  • chalcone synthase
  • RcsB protein, Bacteria
  • antibiotic resistance
  • antibiotic sensitivity
  • article
  • bacterial cell
  • bacterial gene
  • bacterial phenomena and functions
  • bacterial strain
  • bacterium isolate
  • bacterium mutant
  • binding affinity
  • biofilm
  • controlled study
  • flhDC gene
  • gene expression regulation
  • minimum inhibitory concentration
  • nonhuman
  • pmrl gene
  • promoter region
  • protein expression
  • Proteus mirabilis
  • rppA gene
  • signal transduction
  • swarming motility
  • wild type
  • drug effect
  • drug potentiation
  • genetics
  • metabolism
  • microbial sensitivity test
  • mutation
  • Acyltransferases
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Drug Synergism
  • Gene Expression Regulation, Bacterial
  • Hemolysin Proteins
  • Hydroquinones
  • Microbial Sensitivity Tests
  • Mutation
  • Polymyxin B
  • Promoter Regions, Genetic
  • Signal Transduction
  • Virulence Factors

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