title: 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 α-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that the stk deletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Bugrysheva
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Froehlich
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Freiberg
authors.forename: June R
authors.initials: JR
authors.lastname: Scott
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004361:Drug Tolerance; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009220:Myositis / Q000382:microbiology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010406:Penicillins / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010406:Penicillins; D037521:Virulence Factors; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases