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    Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa

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    Author
    Calfee, M. Worth; Coleman, James P.; Pesci, Everett C.
    Abstract
    Pseudomonas aeruginosa is an opportunistic pathogen that controls numerous virulence factors through intercellular signals. This bacterium has two quorum-sensing systems (las and rhl), which act through the intercellular signals N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and N-butyryl-L-homoserine lactone (C4-HSL), respectively. P. aeruginosa also produces a third intercellular signal that is involved in virulence factor regulation. This signal, 2-heptyl-3-hydroxy-4-quinolone [referred to as the Pseudomonas quinolone signal (PQS)], is a secondary metabolite that is part of the P. aeruginosa quorum-sensing hierarchy. PQS can induce both lasB (encodes LasB elastase) and rhlI (encodes the C4-HSL synthase) in P. aeruginosa and is produced maximally during the late stationary phase of growth. Because PQS is an intercellular signal that is part of the quorum-sensing hierarchy and controls multiple virulence factors, we began basic studies designed to elucidate its biosynthetic pathway. First, we present data that strongly suggest that anthranilate is a precursor for PQS. P. aeruginosa converted radiolabeled anthranilate into radioactive PQS, which was bioactive. We also found that an anthranilate analog (methyl anthranilate) would inhibit the production of PQS. This analog was then shown to have a major negative effect on elastase production by P. aeruginosa. These data provide evidence that precursors of intercellular signals may provide viable targets for the development of therapeutic treatments that will reduce P. aeruginosa virulence. Originally published Proceedings of the National Academy of Sciences, Vol. 98, No. 20, Sep 2001
    URI
    http://hdl.handle.net/10342/3240
    Subject
     Pseudomonas quinolone signal; Anthranilate; Intercellular signals 
    Date
    2001-09-25
    Citation:
    APA:
    Calfee, M. Worth, & Coleman, James P., & Pesci, Everett C.. (September 2001). Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences, (98:20), p.11633-11637. Retrieved from http://hdl.handle.net/10342/3240

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Calfee, M. Worth, and Coleman, James P., and Pesci, Everett C.. "Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa". Proceedings of the National Academy of Sciences. 98:20. (11633-11637.), September 2001. March 03, 2021. http://hdl.handle.net/10342/3240.
    Chicago:
    Calfee, M. Worth and Coleman, James P. and Pesci, Everett C., "Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa," Proceedings of the National Academy of Sciences 98, no. 20 (September 2001), http://hdl.handle.net/10342/3240 (accessed March 03, 2021).
    AMA:
    Calfee, M. Worth, Coleman, James P., Pesci, Everett C.. Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences. September 2001; 98(20) 11633-11637. http://hdl.handle.net/10342/3240. Accessed March 03, 2021.
    Collections
    • Microbiology and Immunology
    Publisher
    East Carolina University

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