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Article: Suppression of Staphylococcus aureus virulence by a small-molecule compound

TitleSuppression of Staphylococcus aureus virulence by a small-molecule compound
Authors
Issue Date2018
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2018, v. 115 n. 31, p. 8003-8008 How to Cite?
AbstractEmerging antibiotic resistance among bacterial pathogens has necessitated the development of alternative approaches to combat drug-resistance-associated infection. The abolition of Staphylococcus aureus virulence by targeting multiple-virulence gene products represents a promising strategy for exploration. A multiplex promoter reporter platform using gfp-luxABCDE dual-reporter plasmids with selected promoters from S. aureus-virulence-associated genes was used to identify compounds that modulate the expression of virulence factors. One small-molecule compound, M21, was identified from a chemical library to reverse virulent S. aureus into its nonvirulent state. M21 is a noncompetitive inhibitor of ClpP and alters α-toxin expression in a ClpP-dependent manner. A mouse model of infection indicated that M21 could attenuate S. aureus virulence. This nonantibiotic compound has been shown to suppress the expression of multiple unrelated virulence factors in S. aureus, suggesting that targeting a master regulator of virulence is an effective way to control virulence. Our results illustrate the power of chemical genetics in the modulation of virulence gene expression in pathogenic bacteria.
Persistent Identifierhttp://hdl.handle.net/10722/259395
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorGao, P-
dc.contributor.authorHo, PL-
dc.contributor.authorYan, B-
dc.contributor.authorSze, KH-
dc.contributor.authorDavies, J-
dc.contributor.authorKao, RYT-
dc.date.accessioned2018-09-03T04:06:43Z-
dc.date.available2018-09-03T04:06:43Z-
dc.date.issued2018-
dc.identifier.citationProceedings of the National Academy of Sciences, 2018, v. 115 n. 31, p. 8003-8008-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/259395-
dc.description.abstractEmerging antibiotic resistance among bacterial pathogens has necessitated the development of alternative approaches to combat drug-resistance-associated infection. The abolition of Staphylococcus aureus virulence by targeting multiple-virulence gene products represents a promising strategy for exploration. A multiplex promoter reporter platform using gfp-luxABCDE dual-reporter plasmids with selected promoters from S. aureus-virulence-associated genes was used to identify compounds that modulate the expression of virulence factors. One small-molecule compound, M21, was identified from a chemical library to reverse virulent S. aureus into its nonvirulent state. M21 is a noncompetitive inhibitor of ClpP and alters α-toxin expression in a ClpP-dependent manner. A mouse model of infection indicated that M21 could attenuate S. aureus virulence. This nonantibiotic compound has been shown to suppress the expression of multiple unrelated virulence factors in S. aureus, suggesting that targeting a master regulator of virulence is an effective way to control virulence. Our results illustrate the power of chemical genetics in the modulation of virulence gene expression in pathogenic bacteria.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.titleSuppression of Staphylococcus aureus virulence by a small-molecule compound-
dc.typeArticle-
dc.identifier.emailGao, P: gaopeng@hku.hk-
dc.identifier.emailHo, PL: plho@hku.hk-
dc.identifier.emailYan, B: ybp1205@hku.hk-
dc.identifier.emailSze, KH: khsze@hku.hk-
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hk-
dc.identifier.authorityHo, PL=rp00406-
dc.identifier.authoritySze, KH=rp00785-
dc.identifier.authorityKao, RYT=rp00481-
dc.identifier.doi10.1073/pnas.1720520115-
dc.identifier.pmcidPMC6077739-
dc.identifier.hkuros287778-
dc.identifier.volume115-
dc.identifier.issue31-
dc.identifier.spage8003-
dc.identifier.epage8008-
dc.publisher.placeUnited States-

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