Strain-specific regulatory role of eukaryote-like serine/threonine phosphatase in pneumococcal adherence.
Streptococcus pneumoniae exploits a battery of virulence factors to colonize the host. Although the eukaryote-like Ser/Thr kinase of S. pneumoniae (StkP) has been implicated in physiology and virulence, the role of its cotranscribing phosphatase (PhpP) has remained elusive. The construction of nonpolar markerless phpP knockout mutants (ΔphpP) in two pathogenic strains, D39 (type 2) and 6A-EF3114 (type 6A), indicated that PhpP is not indispensable for pneumococcal survival. Further, PhpP also participates in the regulation of cell wall biosynthesis/division, adherence, and biofilm formation in a strain-specific manner. Additionally, we provide hitherto-unknown in vitro and in vivo evidence of a physiologically relevant biochemical link between the StkP/PhpP-mediated cognate regulation and the two-component regulatory system TCS06 (RR06/HK06) that regulates the expression of the gene encoding an important pneumococcal surface adhesin, CbpA, which was found to be significantly upregulated in ΔphpP mutants. In particular, StkP (threonine)-phosphorylated RR06 bound to the cbpA promoter with high efficiency even in the absence of the HK06-responsive and catalytically active aspartate 51 residue. Together, our findings unravel the significant contributions of PhpP in pneumococcal physiology and adherence.
Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Shivangi
S
Agarwal
Shivani
S
Agarwal
Preeti
P
Pancholi
Vijay
V
Pancholi
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology
D001426:Bacterial Proteins; C490083:CbpA protein, bacteria; D010749:Phosphoprotein Phosphatases