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

doi:10.1371/journal.pone.0045563

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 journal › Article › peer-review

14 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 language	English
Journal	PLoS One
Volume	7
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0045563
Publication status	Published - 2012
Externally published	Yes

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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10.1371/journal.pone.0045563

http://www.scopus.com/inward/record.url?eid=2-s2.0-84866672762&partnerID=40&md5=2377980cc4a6a72a1cccc620b182c269

Cite this

@article{c75bb1dca95f4d749a3e9af47ade2879,

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. {\textcopyright} 2012 Liu et al.",

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",

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

note = "被引用次數：3 Export Date: 16 March 2016 通訊地址: Liaw, S.-J.; Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan; 電子郵件： sjliaw@ntu.edu.tw 化學物質/CAS: ampicillin, 69-52-3, 69-53-4, 7177-48-2, 74083-13-9, 94586-58-0; ciprofloxacin, 85721-33-1; gentamicin, 1392-48-9, 1403-66-3, 1405-41-0; kanamycin, 11025-66-4, 61230-38-4, 8063-07-8; polymyxin B, 1404-26-8, 1405-20-5; streptomycin, 57-92-1; tetracycline, 23843-90-5, 60-54-8, 64-75-5, 8021-86-1; acyltransferase, 9012-30-0, 9054-54-0; chalcone synthase, 56803-04-4; 10'(Z),13'(E)-heptadecadienylhydroquinone; Acyltransferases, 2.3.-; Anti-Bacterial Agents; Bacterial Proteins; Hemolysin Proteins; Hydroquinones; Polymyxin B, 1404-26-8; RcsB protein, Bacteria, 127737-30-8; Virulence Factors; flavanone synthetase, 2.3.1.74 製造商： Fluka, United States 參考文獻: Jacobsen, S.M., Stickler, D.J., Mobley, H.L., Shirtliff, M.E., Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis (2008) Clin Microbiol Rev, 21, pp. 26-59; Mobley, H.L., Chippendale, G.R., Swihart, K.G., Welch, R.A., Cytotoxicity of the HpmA hemolysin and urease of Proteus mirabilis and Proteus vulgaris against cultured human renal proximal tubular epithelial cells (1991) Infect Immun, 59, pp. 2036-2042; Allison, C., Coleman, N., Jones, P.L., Hughes, C., Ability of Proteus mirabilis to invade human urothelial cells is coupled to motility and swarming differentiation (1992) Infect Immun, 60, pp. 4740-4746; Liaw, S.J., Lai, H.C., Ho, S.W., Luh, K.T., Wang, W.B., Inhibition of virulence factor expression and swarming differentiation in Proteus mirabilis by p-nitrophenylglycerol (2000) J Med Microbiol, 49, pp. 725-731; Liaw, S.J., Lai, H.C., Ho, S.W., Luh, K.T., Wang, W.B., Characterisation of p-nitrophenylglycerol-resistant Proteus mirabilis super-swarming mutants (2001) J Med Microbiol, 50, pp. 1039-1048; Liaw, S.J., Lai, H.C., Wang, W.B., Modulation of swarming and virulence by fatty acids through the RsbA protein in Proteus mirabilis (2004) Infect Immun, 72, pp. 6836-6845; Fraser, G.M., Hughes, C., Swarming motility (1999) Curr Opin Microbiol, 2, pp. 630-635; Liaw, S.J., Lai, H.C., Ho, S.W., Luh, K.T., Wang, W.B., Role of RsmA in the regulation of swarming motility and virulence factor expression in Proteus mirabilis (2003) J Med Microbiol, 52, pp. 19-28; Morgenstein, R.M., Szostek, B., Rather, P.N., Regulation of gene expression during swarmer cell differentiation in Proteus mirabilis (2010) FEMS Microbiol Rev, 34, pp. 753-763; Belas, R., Schneider, R., Melch, M., Characterization of Proteus mirabilis precocious swarming mutants: identification of rsbA, encoding a regulator of swarming behavior (1998) J Bacteriol, 180, pp. 6126-6139; Wang, W.B., Lai, H.C., Hsueh, P.R., Chiou, R.Y., Lin, S.B., Inhibition of swarming and virulence factor expression in Proteus mirabilis by resveratrol (2006) J Med Microbiol, 55, pp. 1313-1321; Majdalani, N., Gottesman, S., The Rcs phosphorelay: a complex signal transduction system (2005) Annu Rev Microbiol, 59, pp. 379-405; Takeda, S., Fujisawa, Y., Matsubara, M., Aiba, H., Mizuno, T., A novel feature of the multistep phosphorelay in Escherichia coli: a revised model of the RcsC -> YojN -> RcsB signalling pathway implicated in capsular synthesis and swarming behaviour (2001) Mol Microbiol, 40, pp. 440-450; Clemmer, K.M., Rather, P.N., Regulation of flhDC expression in Proteus mirabilis (2007) Res Microbiol, 158, pp. 295-302; Francez-Charlot, A., Laugel, B., Van Gemert, A., Dubarry, N., Wiorowski, F., RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli (2003) Mol Microbiol, 49, pp. 823-832; Wang, Q., Zhao, Y., McClelland, M., Harshey, R.M., The RcsCDB signaling system and swarming motility in Salmonella enterica serovar Typhimurium: dual regulation of flagellar and SPI-2 virulence genes (2007) J Bacteriol, 189, pp. 8447-8457; Fraser, G.M., Claret, L., Furness, R., Gupta, S., Hughes, C., Swarming-coupled expression of the Proteus mirabilis hpmBA haemolysin operon (2002) Microbiology, 148, pp. 2191-2201; Hancock, R.E., Scott, M.G., The role of antimicrobial peptides in animal defenses (2000) Proc Natl Acad Sci U S A, 97, pp. 8856-8861; Belas, R., Manos, J., Suvanasuthi, R., Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides (2004) Infect Immun, 72, pp. 5159-5167; Phan, V., Belas, R., Gilmore, B.F., Ceri, H., ZapA, a virulence factor in a rat model of Proteus mirabilis-induced acute and chronic prostatitis (2008) Infect Immun, 76, pp. 4859-4864; Walker, K.E., Moghaddame-Jafari, S., Lockatell, C.V., Johnson, D., Belas, R., ZapA, the IgA-degrading metalloprotease of Proteus mirabilis, is a virulence factor expressed specifically in swarmer cells (1999) Mol Microbiol, 32, pp. 825-836; Peschel, A., How do bacteria resist human antimicrobial peptides (2002) Trends Microbiol, 10, pp. 179-186; Gunn, J.S., Lim, K.B., Krueger, J., Kim, K., Guo, L., PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance (1998) Mol Microbiol, 27, pp. 1171-1182; Gunn, J.S., Ryan, S.S., Van Velkinburgh, J.C., Ernst, R.K., Miller, S.I., Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar Typhimurium (2000) Infect Immun, 68, pp. 6139-6146; Wang, W.B., Chen, I.C., Jiang, S.S., Chen, H.R., Hsu, C.Y., Role of RppA in the regulation of polymyxin b susceptibility, swarming, and virulence factor expression in Proteus mirabilis (2008) Infect Immun, 76, pp. 2051-2062; Jiang, S.S., Liu, M.C., Teng, L.J., Wang, W.B., Hsueh, P.R., Proteus mirabilis pmrI, an RppA-regulated gene necessary for polymyxin B resistance, biofilm formation, and urothelial cell invasion (2010) Antimicrob Agents Chemother, 54, pp. 1564-1571; Nordlund, J.J., Grimes, P.E., Ortonne, J.P., The safety of hydroquinone (2006) J Eur Acad Dermatol Venereol, 20, pp. 781-787; Wu, P.L., Lin, S.B., Huang, C.P., Chiou, R.Y., Antioxidative and cytotoxic compounds extracted from the sap of Rhus succedanea (2002) J Nat Prod, 65, pp. 1719-1721; Chen, Y.R., Y-Y, R., Lin, T.Y., Huang, C.P., Tang, W.C., Identification of an Alkylhydroquinone from Rhus succedanea as an Inhibitor of Tyrosinase and Melanogenesis (2009) J Agric Food Chem, 57, pp. 2200-2205; Huang, C.P., Fang, W.H., Lin, L.I., Chiou, R.Y., Kan, L.S., Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning (2008) Toxicol Appl Pharmacol, 227, pp. 331-338; Qiu, J., Wang, D., Xiang, H., Feng, H., Jiang, Y., Subinhibitory concentrations of thymol reduce enterotoxins A and B and alpha-hemolysin production in Staphylococcus aureus isolates (2010) PLoS One, 5, pp. e9736; Gotoh, Y., Eguchi, Y., Watanabe, T., Okamoto, S., Doi, A., Two-component signal transduction as potential drug targets in pathogenic bacteria (2010) Curr Opin Microbiol, 13, pp. 232-239; Belas, R., Erskine, D., Flaherty, D., Transposon mutagenesis in Proteus mirabilis (1991) J Bacteriol, 173, pp. 6289-6293; Jiang, S.S., Lin, T.Y., Wang, W.B., Liu, M.C., Hsueh, P.R., Characterization of UDP-glucose dehydrogenase and UDP-glucose pyrophosphorylase mutants of Proteus mirabilis: defectiveness in polymyxin B resistance, swarming, and virulence (2010) Antimicrob Agents Chemother, 54, pp. 2000-2009; (2009) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, , Clinical and Laboratory Standards Institute, approved standard M07-A8 teC, Wayne, PA; Lee, S., Hinz, A., Bauerle, E., Angermeyer, A., Juhaszova, K., Targeting a bacterial stress response to enhance antibiotic action (2009) Proc Natl Acad Sci U S A, 106, pp. 14570-14575; Pescaretti, M.L., Lopez, F.E., Morero, R.D., Delgado, M.A., Transcriptional autoregulation of the RcsCDB phosphorelay system in Salmonella enterica serovar Typhimurium (2010) Microbiology, 156, pp. 3513-3521; Kim, W., Killam, T., Sood, V., Surette, M.G., Swarm-cell differentiation in Salmonella enterica serovar Typhimurium results in elevated resistance to multiple antibiotics (2003) J Bacteriol, 185, pp. 3111-3117; Parsek, M.R., Singh, P.K., Bacterial biofilms: an emerging link to disease pathogenesis (2003) Annu Rev Microbiol, 57, pp. 677-701; Morgenstein, R.M., Clemmer, K.M., Rather, P.N., Loss of the waaL O-antigen ligase prevents surface activation of the flagellar gene cascade in Proteus mirabilis (2010) J Bacteriol, 192, pp. 3213-3221; Pandey, D.K., Mishra, N., Singh, P., Relative phytotoxicity of hydroquinone on rice (Oryza sativa L.) and associated aquatic weed green musk chara (Chara zeylanica Willd.) (2005) Pestic Biochem Physiol, 83, pp. 82-96; Zhang, Y., Lucocq, J.M., Hayes, J.D., The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors (2009) Biochem J, 418, pp. 293-310; Maresh, J., Zhang, J., Tzeng, Y.L., Goodman, N.A., Lynn, D.G., Rational design of inhibitors of VirA-VirG two-component signal transduction (2007) Bioorg Med Chem Lett, 17, pp. 3281-3286",

year = "2012",

doi = "10.1371/journal.pone.0045563",

language = "English",

volume = "7",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

TY - JOUR

T1 - 10′(Z),13′(E)-Heptadecadienylhydroquinone Inhibits Swarming and Virulence Factors and Increases Polymyxin B Susceptibility in Proteus mirabilis

AU - Liu, Ming-Che

AU - Lin, Shwu-Bin

AU - Chien, Hsiung-Fei

AU - Wang, Won-Bo

AU - Yuan, Yu-Han

AU - Hsueh, Po-Ren

AU - Liaw, Shwu-Jen

N1 - 被引用次數：3 Export Date: 16 March 2016 通訊地址: Liaw, S.-J.; Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan; 電子郵件： sjliaw@ntu.edu.tw 化學物質/CAS: ampicillin, 69-52-3, 69-53-4, 7177-48-2, 74083-13-9, 94586-58-0; ciprofloxacin, 85721-33-1; gentamicin, 1392-48-9, 1403-66-3, 1405-41-0; kanamycin, 11025-66-4, 61230-38-4, 8063-07-8; polymyxin B, 1404-26-8, 1405-20-5; streptomycin, 57-92-1; tetracycline, 23843-90-5, 60-54-8, 64-75-5, 8021-86-1; acyltransferase, 9012-30-0, 9054-54-0; chalcone synthase, 56803-04-4; 10'(Z),13'(E)-heptadecadienylhydroquinone; Acyltransferases, 2.3.-; Anti-Bacterial Agents; Bacterial Proteins; Hemolysin Proteins; Hydroquinones; Polymyxin B, 1404-26-8; RcsB protein, Bacteria, 127737-30-8; Virulence Factors; flavanone synthetase, 2.3.1.74 製造商： Fluka, United States 參考文獻: Jacobsen, S.M., Stickler, D.J., Mobley, H.L., Shirtliff, M.E., Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis (2008) Clin Microbiol Rev, 21, pp. 26-59; Mobley, H.L., Chippendale, G.R., Swihart, K.G., Welch, R.A., Cytotoxicity of the HpmA hemolysin and urease of Proteus mirabilis and Proteus vulgaris against cultured human renal proximal tubular epithelial cells (1991) Infect Immun, 59, pp. 2036-2042; Allison, C., Coleman, N., Jones, P.L., Hughes, C., Ability of Proteus mirabilis to invade human urothelial cells is coupled to motility and swarming differentiation (1992) Infect Immun, 60, pp. 4740-4746; Liaw, S.J., Lai, H.C., Ho, S.W., Luh, K.T., Wang, W.B., Inhibition of virulence factor expression and swarming differentiation in Proteus mirabilis by p-nitrophenylglycerol (2000) J Med Microbiol, 49, pp. 725-731; Liaw, S.J., Lai, H.C., Ho, S.W., Luh, K.T., Wang, W.B., Characterisation of p-nitrophenylglycerol-resistant Proteus mirabilis super-swarming mutants (2001) J Med Microbiol, 50, pp. 1039-1048; Liaw, S.J., Lai, H.C., Wang, W.B., Modulation of swarming and virulence by fatty acids through the RsbA protein in Proteus mirabilis (2004) Infect Immun, 72, pp. 6836-6845; Fraser, G.M., Hughes, C., Swarming motility (1999) Curr Opin Microbiol, 2, pp. 630-635; Liaw, S.J., Lai, H.C., Ho, S.W., Luh, K.T., Wang, W.B., Role of RsmA in the regulation of swarming motility and virulence factor expression in Proteus mirabilis (2003) J Med Microbiol, 52, pp. 19-28; Morgenstein, R.M., Szostek, B., Rather, P.N., Regulation of gene expression during swarmer cell differentiation in Proteus mirabilis (2010) FEMS Microbiol Rev, 34, pp. 753-763; Belas, R., Schneider, R., Melch, M., Characterization of Proteus mirabilis precocious swarming mutants: identification of rsbA, encoding a regulator of swarming behavior (1998) J Bacteriol, 180, pp. 6126-6139; Wang, W.B., Lai, H.C., Hsueh, P.R., Chiou, R.Y., Lin, S.B., Inhibition of swarming and virulence factor expression in Proteus mirabilis by resveratrol (2006) J Med Microbiol, 55, pp. 1313-1321; Majdalani, N., Gottesman, S., The Rcs phosphorelay: a complex signal transduction system (2005) Annu Rev Microbiol, 59, pp. 379-405; Takeda, S., Fujisawa, Y., Matsubara, M., Aiba, H., Mizuno, T., A novel feature of the multistep phosphorelay in Escherichia coli: a revised model of the RcsC -> YojN -> RcsB signalling pathway implicated in capsular synthesis and swarming behaviour (2001) Mol Microbiol, 40, pp. 440-450; Clemmer, K.M., Rather, P.N., Regulation of flhDC expression in Proteus mirabilis (2007) Res Microbiol, 158, pp. 295-302; Francez-Charlot, A., Laugel, B., Van Gemert, A., Dubarry, N., Wiorowski, F., RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli (2003) Mol Microbiol, 49, pp. 823-832; Wang, Q., Zhao, Y., McClelland, M., Harshey, R.M., The RcsCDB signaling system and swarming motility in Salmonella enterica serovar Typhimurium: dual regulation of flagellar and SPI-2 virulence genes (2007) J Bacteriol, 189, pp. 8447-8457; Fraser, G.M., Claret, L., Furness, R., Gupta, S., Hughes, C., Swarming-coupled expression of the Proteus mirabilis hpmBA haemolysin operon (2002) Microbiology, 148, pp. 2191-2201; Hancock, R.E., Scott, M.G., The role of antimicrobial peptides in animal defenses (2000) Proc Natl Acad Sci U S A, 97, pp. 8856-8861; Belas, R., Manos, J., Suvanasuthi, R., Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides (2004) Infect Immun, 72, pp. 5159-5167; Phan, V., Belas, R., Gilmore, B.F., Ceri, H., ZapA, a virulence factor in a rat model of Proteus mirabilis-induced acute and chronic prostatitis (2008) Infect Immun, 76, pp. 4859-4864; Walker, K.E., Moghaddame-Jafari, S., Lockatell, C.V., Johnson, D., Belas, R., ZapA, the IgA-degrading metalloprotease of Proteus mirabilis, is a virulence factor expressed specifically in swarmer cells (1999) Mol Microbiol, 32, pp. 825-836; Peschel, A., How do bacteria resist human antimicrobial peptides (2002) Trends Microbiol, 10, pp. 179-186; Gunn, J.S., Lim, K.B., Krueger, J., Kim, K., Guo, L., PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance (1998) Mol Microbiol, 27, pp. 1171-1182; Gunn, J.S., Ryan, S.S., Van Velkinburgh, J.C., Ernst, R.K., Miller, S.I., Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar Typhimurium (2000) Infect Immun, 68, pp. 6139-6146; Wang, W.B., Chen, I.C., Jiang, S.S., Chen, H.R., Hsu, C.Y., Role of RppA in the regulation of polymyxin b susceptibility, swarming, and virulence factor expression in Proteus mirabilis (2008) Infect Immun, 76, pp. 2051-2062; Jiang, S.S., Liu, M.C., Teng, L.J., Wang, W.B., Hsueh, P.R., Proteus mirabilis pmrI, an RppA-regulated gene necessary for polymyxin B resistance, biofilm formation, and urothelial cell invasion (2010) Antimicrob Agents Chemother, 54, pp. 1564-1571; Nordlund, J.J., Grimes, P.E., Ortonne, J.P., The safety of hydroquinone (2006) J Eur Acad Dermatol Venereol, 20, pp. 781-787; Wu, P.L., Lin, S.B., Huang, C.P., Chiou, R.Y., Antioxidative and cytotoxic compounds extracted from the sap of Rhus succedanea (2002) J Nat Prod, 65, pp. 1719-1721; Chen, Y.R., Y-Y, R., Lin, T.Y., Huang, C.P., Tang, W.C., Identification of an Alkylhydroquinone from Rhus succedanea as an Inhibitor of Tyrosinase and Melanogenesis (2009) J Agric Food Chem, 57, pp. 2200-2205; Huang, C.P., Fang, W.H., Lin, L.I., Chiou, R.Y., Kan, L.S., Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning (2008) Toxicol Appl Pharmacol, 227, pp. 331-338; Qiu, J., Wang, D., Xiang, H., Feng, H., Jiang, Y., Subinhibitory concentrations of thymol reduce enterotoxins A and B and alpha-hemolysin production in Staphylococcus aureus isolates (2010) PLoS One, 5, pp. e9736; Gotoh, Y., Eguchi, Y., Watanabe, T., Okamoto, S., Doi, A., Two-component signal transduction as potential drug targets in pathogenic bacteria (2010) Curr Opin Microbiol, 13, pp. 232-239; Belas, R., Erskine, D., Flaherty, D., Transposon mutagenesis in Proteus mirabilis (1991) J Bacteriol, 173, pp. 6289-6293; Jiang, S.S., Lin, T.Y., Wang, W.B., Liu, M.C., Hsueh, P.R., Characterization of UDP-glucose dehydrogenase and UDP-glucose pyrophosphorylase mutants of Proteus mirabilis: defectiveness in polymyxin B resistance, swarming, and virulence (2010) Antimicrob Agents Chemother, 54, pp. 2000-2009; (2009) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, , Clinical and Laboratory Standards Institute, approved standard M07-A8 teC, Wayne, PA; Lee, S., Hinz, A., Bauerle, E., Angermeyer, A., Juhaszova, K., Targeting a bacterial stress response to enhance antibiotic action (2009) Proc Natl Acad Sci U S A, 106, pp. 14570-14575; Pescaretti, M.L., Lopez, F.E., Morero, R.D., Delgado, M.A., Transcriptional autoregulation of the RcsCDB phosphorelay system in Salmonella enterica serovar Typhimurium (2010) Microbiology, 156, pp. 3513-3521; Kim, W., Killam, T., Sood, V., Surette, M.G., Swarm-cell differentiation in Salmonella enterica serovar Typhimurium results in elevated resistance to multiple antibiotics (2003) J Bacteriol, 185, pp. 3111-3117; Parsek, M.R., Singh, P.K., Bacterial biofilms: an emerging link to disease pathogenesis (2003) Annu Rev Microbiol, 57, pp. 677-701; Morgenstein, R.M., Clemmer, K.M., Rather, P.N., Loss of the waaL O-antigen ligase prevents surface activation of the flagellar gene cascade in Proteus mirabilis (2010) J Bacteriol, 192, pp. 3213-3221; Pandey, D.K., Mishra, N., Singh, P., Relative phytotoxicity of hydroquinone on rice (Oryza sativa L.) and associated aquatic weed green musk chara (Chara zeylanica Willd.) (2005) Pestic Biochem Physiol, 83, pp. 82-96; Zhang, Y., Lucocq, J.M., Hayes, J.D., The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors (2009) Biochem J, 418, pp. 293-310; Maresh, J., Zhang, J., Tzeng, Y.L., Goodman, N.A., Lynn, D.G., Rational design of inhibitors of VirA-VirG two-component signal transduction (2007) Bioorg Med Chem Lett, 17, pp. 3281-3286

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - 10',13' heptadecadienylhydroquinone

KW - ampicillin

KW - bacterial protein

KW - ciprofloxacin

KW - gentamicin

KW - hemolysin

KW - hydroquinone derivative

KW - kanamycin

KW - lipopolysaccharide

KW - polymyxin B

KW - protein rcsB

KW - protein rppA

KW - streptomycin

KW - tetracycline

KW - unclassified drug

KW - virulence factor

KW - 10'(Z),13'(E) heptadecadienylhydroquinone

KW - 10'(Z),13'(E)-heptadecadienylhydroquinone

KW - acyltransferase

KW - antiinfective agent

KW - chalcone synthase

KW - RcsB protein, Bacteria

KW - antibiotic resistance

KW - antibiotic sensitivity

KW - article

KW - bacterial cell

KW - bacterial gene

KW - bacterial phenomena and functions

KW - bacterial strain

KW - bacterium isolate

KW - bacterium mutant

KW - binding affinity

KW - biofilm

KW - controlled study

KW - flhDC gene

KW - gene expression regulation

KW - minimum inhibitory concentration

KW - nonhuman

KW - pmrl gene

KW - promoter region

KW - protein expression

KW - Proteus mirabilis

KW - rppA gene

KW - signal transduction

KW - swarming motility

KW - wild type

KW - drug effect

KW - drug potentiation

KW - genetics

KW - metabolism

KW - microbial sensitivity test

KW - mutation

KW - Acyltransferases

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Drug Synergism

KW - Gene Expression Regulation, Bacterial

KW - Hemolysin Proteins

KW - Hydroquinones

KW - Microbial Sensitivity Tests

KW - Mutation

KW - Polymyxin B

KW - Promoter Regions, Genetic

KW - Signal Transduction

KW - Virulence Factors

U2 - 10.1371/journal.pone.0045563

DO - 10.1371/journal.pone.0045563

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

ER -

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

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