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

• Published in: PloS one Vol. 7; no. 9; p. e45563
• Main Authors: Liu, Ming-Che, Lin, Shwu-Bin, Chien, Hsiung-Fei, Wang, Won-Bo, Yuan, Yu-Han, Hsueh, Po-Ren, Liaw, Shwu-Jen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.09.2012; Public Library of Science (PLoS)
• Subjects: Acyltransferases - genetics; Anti-Bacterial Agents - pharmacology; Antigens; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilms; Biological effects; Biology; Biotechnology; Cancer; Clinical isolates; Cosmetics; Cytotoxicity; Drug Synergism; Gene expression; Gene Expression Regulation, Bacterial; Genes; Hemolysin Proteins - metabolism; Hospitals; Hydroquinones - pharmacology; Inhibition; Kinases; Laboratories; Lipopolysaccharides; Microbial Sensitivity Tests; Mutants; Mutation; Pathogenesis; Poisons; Polymyxin B; Polymyxin B - pharmacology; Promoter Regions, Genetic - drug effects; Proteins; Proteus mirabilis - drug effects; Proteus mirabilis - genetics; Proteus mirabilis - metabolism; Salmonella; Salmonella Typhimurium; Signal Transduction; Signaling; Swarming; Therapeutic applications; Urogenital system; Virulence; Virulence factors; Virulence Factors - genetics; Virulence Factors - metabolism; China; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045563

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.