|Title||Identification of a Molecular Latch that Regulates Staphylococcal Virulence.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Xie, Q, Zhao, A, Jeffrey, PD, Kim, MKevin, Bassler, BL, Stone, HA, Novick, RP, Muir, TW|
|Journal||Cell Chem Biol|
|Date Published||2019 Jan 31|
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.
|Alternate Journal||Cell Chem Biol|