An intramembrane sensory circuit monitors sortase A–mediated processing of streptococcal adhesins

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Science Signaling  07 May 2019:
Vol. 12, Issue 580, eaas9941
DOI: 10.1126/scisignal.aas9941

Quality control in bacterial adhesion

Adhesins mediate bacterial adhesion and are often required for host colonization. As adhesins of the LPXTG family are exported and covalently linked to the cell wall, the LPXTG motif is cleaved, producing a C-terminal peptide (C-pep) that remains embedded in the cell membrane. Hall et al. found that the presence of C-peps from the LPXTG adhesins of Streptococcus gordonii, which are found in oral microbial biofilms and can cause infective endocarditis after entering the bloodstream, inhibited the expression of alternative adhesins through a two-component system (TCS). In the absence of C-peps from LPXTG adhesins, the TCS stimulated the expression of alternative adhesins that supported biofilm formation. This intramembrane quality control mechanism ensures that S. gordonii can form biofilms under various environmental conditions.


Bacterial adhesins mediate adhesion to substrates and biofilm formation. Adhesins of the LPXTG family are posttranslationally processed by the cell membrane–localized peptidase sortase A, which cleaves the LPXTG motif. This generates a short C-terminal peptide (C-pep) that remains in the cell membrane, whereas the mature adhesin is incorporated into the cell wall. Genes encoding adhesins of the oral bacterium Streptococcus gordonii were differentially expressed depending on whether the bacteria were isolated from saliva or dental plaque and appeared to be coordinately regulated. Deletion of sspA and sspB (sspAB), both of which encode LPXTG-containing adhesins, unexpectedly enhanced adhesion and biofilm formation. C-peps produced from a model LPXTG-containing adhesin localized to the cell membrane and bound to and inhibited the intramembrane sensor histidine kinase SGO_1180, thus preventing activation of the cognate response regulator SGO_1181. The absence of SspAB C-peps induced the expression of the scaCBA operon encoding the lipoprotein adhesin ScaA, which was sufficient to preserve and even enhance biofilm formation. This C-pep–driven regulatory circuit also exists in pathogenic streptococci and is likely conserved among Gram-positive bacteria. This quality control mechanism ensures that the bacteria can form biofilms under diverse environmental conditions and may play a role in optimizing adhesion and biofilm formation.

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