title: MgrA activates expression of capsule genes, but not the α-toxin gene in experimental Staphylococcus aureus endocarditis.
abstract: BACKGROUND
  Staphylococcus aureus produces numerous virulence factors but little is known about their in vivo regulation during an infection.
  
  
  METHODS
  The production of capsule and α-toxin, and the expression of their respective genes, cap5 and hla, were analyzed by comparing CYL11481 (derivative of Newman) and its isogenic regulatory mutants in vitro. The temporal expression of cap5 and hla and the regulatory genes in vivo was carried out using a rat infective endocarditis model.
  
  
  RESULTS
  In vitro analyses showed that capsule was positively regulated by MgrA, Agr, Sae, ArlR, and ClpC, and negatively by CodY and SbcDC. The α-toxin was positively regulated by MgrA, Agr, Sae, ArlR, and SbcDC but negatively by ClpC and CodY. In vivo analyses showed that cap5 expression correlated best with mgrA expression, whereas hla expression correlated best with sae expression. Mutation in mgrA drastically reduced cap5 expression in vivo.
  
  
  CONCLUSIONS
  Our results suggest that, in vitro, Agr is the most important regulator for capsule and α-toxin production, as well as for cap5 transcription, but SaeR is the most critical for hla transcription. However, in vivo, MgrA is the major transcriptional regulator of capsule, but not α-toxin, whereas saeR expression correlates best with hla expression.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock.
authors.forename: Ravi Kr
authors.initials: RK
authors.lastname: Gupta
authors.forename: Jimena
authors.initials: J
authors.lastname: Alba
authors.forename: Yan Q
authors.initials: YQ
authors.lastname: Xiong
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017384:Sequence Deletion; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C107803:Cap5 protein, Staphylococcus; D006460:Hemolysin Proteins; D015534:Trans-Activators; D037521:Virulence Factors; C021091:staphylococcal alpha-toxin
keywords: Staphylococcus aureus; capsule; infective endocarditis model; mgrA; virulence; α-toxin
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