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Identification of a Molecular Latch that Regulates Staphylococcal Virulence.

ABSTRACT: Virulence induction in the Staphylococcus aureus is under the control of a quorum sensing (QS) circuit encoded by the accessory gene regulator (agr) locus. Allelic variation within agr produces four QS specificity groups, each producing a unique secreted autoinducer peptide (AIP) and receptor histidine kinase (RHK), AgrC. Cognate AIP-AgrC interactions activate virulence through a two-component signaling cascade, whereas non-cognate pairs are generally inhibitory. Here we pinpoint a key hydrogen-bonding interaction within AgrC that acts as a switch to convert helical motions propagating from the receptor sensor domain into changes in inter-domain association within the kinase module. AgrC mutants lacking this interaction are constitutively active in vitro and in vivo, the latter leading to a pronounced attenuation of S. aureus biofilm formation. Thus, our work sheds light on the regulation of this biomedically important RHK.

SUBMITTER: Xie Q

PROVIDER: S-EPMC6506218 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Identification of a Molecular Latch that Regulates Staphylococcal Virulence.

Xie Qian Q Zhao Aishan A Jeffrey Philip D PD Kim Minyoung Kevin MK Bassler Bonnie L BL Stone Howard A HA Novick Richard P RP Muir Tom W TW

Cell chemical biology 20190214 4

Virulence induction in the Staphylococcus aureus is under the control of a quorum sensing (QS) circuit encoded by the accessory gene regulator (agr) locus. Allelic variation within agr produces four QS specificity groups, each producing a unique secreted autoinducer peptide (AIP) and receptor histidine kinase (RHK), AgrC. Cognate AIP-AgrC interactions activate virulence through a two-component signaling cascade, whereas non-cognate pairs are generally inhibitory. Here we pinpoint a key hydrogen- ...[more]

PMID: 30773482

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