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The S treptococcus pyogenes orphan protein tyrosine phosphatase, SP‐PTP , possesses dual specificity and essential virulence regulatory functions
Author(s) -
Kant Sashi,
Agarwal Shivani,
Pancholi Preeti,
Pancholi Vijay
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13047
Subject(s) - biology , phosphorylation , protein tyrosine phosphatase , phosphatase , mutant , virulence , tyrosine phosphorylation , tyrosine , gene , protein phosphatase 2 , microbiology and biotechnology , biochemistry
Summary G roup A S treptococcus ( GAS ) is a human pathogen that causes high morbidity and mortality. GAS lacks a gene encoding tyrosine kinase but contains one encoding tyrosine phosphatase ( SP‐PTP ). Thus, GAS is thought to lack tyrosine phosphorylation, and the physiological significance of SP‐PTP is, therefore, questionable. Here, we demonstrate that SP‐PTP possesses dual phosphatase specificity for T yr‐ and S er/ T hr‐phosphorylated GAS proteins, such as S er/ T hr kinase ( SP‐STK ) and the SP‐STK ‐phosphorylated CovR and WalR proteins. Phenotypic analysis of GAS mutants lacking SP‐PTP revealed that the phosphatase activity per se positively regulates growth, cell division and the ability to adhere to and invade host cells. Furthermore, A549 human lung cells infected with GAS mutants lacking SP‐PTP displayed increased S er‐/ T hr‐/ T yr‐phosphorylation. SP‐PTP also differentially regulates the expression of ∼50% of the total GAS genes, including several virulence genes potentially through the two‐component regulators, CovR , WalR and PTS / HPr regulation of M ga. Although these mutants exhibit attenuated virulence, a GAS mutant overexpressing SP‐PTP is hypervirulent. Our study provides the first definitive evidence for the presence and importance of Tyr‐phosphorylation in GAS and the relevance of SP‐PTP as an important therapeutic target.