title: Role of Mga in group A streptococcal infection at the skin epithelium.
abstract: Group A streptococci (GAS) primarily cause infection at epithelial tissue sites of its human host. The role of the transcriptional regulator Mga in a humanized mouse model for superficial skin infection was investigated. Inactivation of mga in a skin strain (Alab49) led to loss of virulence. The Deltamga mutant displayed >100-fold decrease in emm (pam) transcript levels, and loss of bacterial-bound plasmin activity. A slight decrease in speB transcription, accompanied by a partial decrease in cysteine protease activity but no change in PrtF2 degradation, was also observed. Mga had no effect on transcription of nra, Nra-regulated pilus genes (cpa, fctA) or other FCT-region genes (msmR, prtF2). Combined with findings on other Alab49 mutants, data show that several essential virulence genes are regulated by Mga or Nra, but not both, implying that any coordinated response during skin infection likely operates at a higher level of transcriptional control. Mga was required for bacterial autoaggregation and biofilm-like growth on an abiotic surface; however, aggregation and biofilm formation have only partial overlap with the skin virulence phenotype. Findings on numerous phenotypes for 7 mutants constructed on the same genetic background yield a detailed, integrated model for GAS pathogenesis at the skin.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: Sergio
authors.initials: S
authors.lastname: Lizano
authors.forename: Sukalyani
authors.initials: S
authors.lastname: Banik
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Debra E
authors.initials: DE
authors.lastname: Bessen
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D004848:Epithelium / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D016513:Mice, SCID; D013207:Staphylococcal Skin Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C068267:mry protein, Streptococcus pyogenes