2011
DOI: 10.1128/iai.05360-11
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Serine/Threonine Protein Kinase Stk Is Required for Virulence, Stress Response, and Penicillin Tolerance in Streptococcus pyogenes

Abstract: Genes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogen Streptococcus pyogenes (group A streptococcus [GAS]). We report that in GAS, stk is required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of ␣-glucans, and fatty acid biosynthesis, as well as gene… Show more

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Cited by 43 publications
(53 citation statements)
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“…Our study showing increased fatty acid biosynthesis in the M1⌬STP mutant is in agreement with the recently demonstrated role of SP-STK in positively regulating fatty acid biosynthesis (42). This highlights another level of cognate regulation mediated by this SP-STK/STP couple in controlling metabolic processes within GAS and is speculated to be manifested by SP-STK-mediated phosphorylation of the fabT repressor.…”
Section: Discussionsupporting
confidence: 77%
“…Our study showing increased fatty acid biosynthesis in the M1⌬STP mutant is in agreement with the recently demonstrated role of SP-STK in positively regulating fatty acid biosynthesis (42). This highlights another level of cognate regulation mediated by this SP-STK/STP couple in controlling metabolic processes within GAS and is speculated to be manifested by SP-STK-mediated phosphorylation of the fabT repressor.…”
Section: Discussionsupporting
confidence: 77%
“…Interestingly, two independent PBr mutations altered the same serine residue at position 84 of FabT (S84L), a potential target of the Stk/Stp serine/threonine kinase/phosphatase of S. pyogenes (56,57). Stk regulation of FabT alters membrane fatty acid composition (56) and contributes to resistance to several types of stress (57), further implicating a link between FabT, stress response, and ExPortal integrity.…”
Section: Discussionmentioning
confidence: 99%
“…4 However, most subsequent studies have focused on these signaling cascades as being indispensable for virulence in a variety of human pathogens. [5][6][7][8][9][10][11][12][13][14][15] The 'genomic age' has revealed a considerable expansion of the eSTK protein family and the presence of their cognate eSTPs in most prokaryotic Phylums, which include important Gram-negative human pathogens such as Pseudomonas aeruginosa, 9,16 and many Gram-positives such as Enterococcus faecalis, 17 Staphylococcus aureus, 12,14,[18][19][20] Mycobacterium tuberculosis, 6,21,22 Streptococcus pneumoniae, 7,23,24 Streptococcus agalactiae 8 and Streptococcus pyogenes. 10,25 This discovery led to the realization that unlike TCS histidine kinases, which almost exclusively target a single response regulator partner, eSTK substrates are instead quite pleiotropic in nature.…”
Section: Eukaryotic-like Serine-threonine Kinases (Estks) and Phosphamentioning
confidence: 99%
“…GAS, GBS and S. pneumoniae each possess only a single predicted PASTA domain-containing eSTK/eSTP pair, called Stk1 in GAS/GBS and StkP in S. pneumoniae, all of which are required for infection 7,8,13,25 (reviewed by Burnside and Rajagopal in ref. 133 ).…”
Section: Streptococcimentioning
confidence: 99%