PMID- 22311926 OWN - NLM STAT- MEDLINE DCOM- 20120510 LR - 20211021 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 80 IP - 4 DP - 2012 Apr TI - Strain-specific regulatory role of eukaryote-like serine/threonine phosphatase in pneumococcal adherence. PG - 1361-72 LID - 10.1128/IAI.06311-11 [doi] AB - 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 (DeltaphpP) 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 DeltaphpP 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. FAU - Agarwal, Shivangi AU - Agarwal S AD - Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio, USA. FAU - Agarwal, Shivani AU - Agarwal S FAU - Pancholi, Preeti AU - Pancholi P FAU - Pancholi, Vijay AU - Pancholi V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120206 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Bacterial Proteins) RN - 0 (CbpA protein, bacteria) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) SB - IM MH - *Bacterial Adhesion MH - Bacterial Proteins/biosynthesis/genetics/*metabolism MH - Biofilms/growth & development MH - Cell Line MH - Gene Expression Regulation, Bacterial MH - Gene Knockout Techniques MH - Humans MH - Phosphoprotein Phosphatases/genetics/*metabolism MH - Signal Transduction MH - Streptococcus pneumoniae/*enzymology/genetics/pathogenicity/physiology PMC - PMC3318399 EDAT- 2012/02/09 06:00 MHDA- 2012/05/11 06:00 PMCR- 2012/10/01 CRDT- 2012/02/08 06:00 PHST- 2012/02/08 06:00 [entrez] PHST- 2012/02/09 06:00 [pubmed] PHST- 2012/05/11 06:00 [medline] PHST- 2012/10/01 00:00 [pmc-release] AID - IAI.06311-11 [pii] AID - 06311-11 [pii] AID - 10.1128/IAI.06311-11 [doi] PST - ppublish SO - Infect Immun. 2012 Apr;80(4):1361-72. doi: 10.1128/IAI.06311-11. Epub 2012 Feb 6.