2020
DOI: 10.1371/journal.ppat.1008867
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Cytotoxic alkyl-quinolones mediate surface-induced virulence in Pseudomonas aeruginosa

Abstract: Surface attachment, an early step in the colonization of multiple host environments, activates the virulence of the human pathogen P. aeruginosa. However, the downstream toxins that mediate surface-dependent P. aeruginosa virulence remain unclear, as do the signaling pathways that lead to their activation. Here, we demonstrate that alkyl-quinolone (AQ) secondary metabolites are rapidly induced upon surface association and act directly on host cells to cause cytotoxicity. Surface-induced AQ cytotoxicity is inde… Show more

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Cited by 18 publications
(26 citation statements)
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“…OMVs facilitate the delivery of several virulence factors simultaneously, directly into the cytoplasm of host cells [41,42]. Such virulence factors include alkaline phosphatase, haemolytic phospholipase C, the toxin Cif, and cytotoxic alkyl quinolones [41,46]. Likewise, alkyl quinolones acting as QS molecules are also trafficked between bacteria in OMVs [47,48].…”
Section: Virulence Factors In Pseudomonas Aeruginosamentioning
confidence: 99%
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“…OMVs facilitate the delivery of several virulence factors simultaneously, directly into the cytoplasm of host cells [41,42]. Such virulence factors include alkaline phosphatase, haemolytic phospholipase C, the toxin Cif, and cytotoxic alkyl quinolones [41,46]. Likewise, alkyl quinolones acting as QS molecules are also trafficked between bacteria in OMVs [47,48].…”
Section: Virulence Factors In Pseudomonas Aeruginosamentioning
confidence: 99%
“…The mechanism by which surface-attached cells induce virulence towards host cells is thought to be multifactorial [46,64]. LasR is an important regulator of surface-attached virulence: upon surface attachment, lasR expression is up-regulated and the induction of LasR targets in response to the las QSSM, 3oC12-HSL, is stronger than in planktonic bacteria [65].…”
Section: The Importance Of Surface Attachmentmentioning
confidence: 99%
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“…10 Although the exact roles of MAQs in the Burkholderia cepacia complex still need to be investigated, the homologous AQs of P. aeruginosa indicate possible roles in suppressing the host immune response, mediating the killing of host cells and modulating interspecies and interkingdom interactions. [22][23][24]…”
Section: †)mentioning
confidence: 99%
“…2a). We synthesized several a-chloroketones (1-4) using the Houben-Hoesch reaction (Scheme 1) and combined them with commercially available compounds (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) to generate a small library (Fig. 2b).…”
mentioning
confidence: 99%