title: 10'(Z),13'(E)-heptadecadienylhydroquinone inhibits swarming and virulence factors and increases polymyxin B susceptibility in Proteus mirabilis.
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.
authors.affiliation: Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Liu
authors.forename: Shwu-Bin
authors.initials: SB
authors.lastname: Lin
authors.forename: Hsiung-Fei
authors.initials: HF
authors.lastname: Chien
authors.forename: Won-Bo
authors.initials: WB
authors.lastname: Wang
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Yuan
authors.forename: Po-Ren
authors.initials: PR
authors.lastname: Hsueh
authors.forename: Shwu-Jen
authors.initials: SJ
authors.lastname: Liaw
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011112:Polymyxin B / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011513:Proteus mirabilis / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C471675:10'(Z),13'(E)-heptadecadienylhydroquinone; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D006873:Hydroquinones; D037521:Virulence Factors; C074889:RcsB protein, Bacteria; D000217:Acyltransferases; C020141:flavanone synthetase; D011112:Polymyxin B