The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community. Currently, we have limited understanding of mechanisms of innate immune evasion used by S. aureus. To that end, we created an isogenic deletion mutant in strain MW2 (USA400) of the saeR/S 2-component gene regulatory system and studied its role in mouse models of pathogenesis and during human neutrophil interaction. In this study, we demonstrate that saeR/S plays a distinct role in S. aureus pathogenesis and is vital for virulence of MW2 in a mouse model of sepsis. Moreover, deletion of saeR/S significantly impaired survival of MW2 in human blood and after neutrophil phagocytosis. Microarray analysis revealed that SaeR/S of MW2 influences expression of a wide variety of genes with diverse biological functions. These data provide new insight into how virulence is regulated in S. aureus and associates a specific staphylococcal gene-regulatory system with invasive staphylococcal disease.
Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA. jovanka@montana.edu
Jovanka M
JM
Voyich
Cuong
C
Vuong
Mark
M
DeWald
Tyler K
TK
Nygaard
Stanislava
S
Kocianova
Shannon
S
Griffith
Jennifer
J
Jones
Courtney
C
Iverson
Daniel E
DE
Sturdevant
Kevin R
KR
Braughton
Adeline R
AR
Whitney
Michael
M
Otto
Frank R
FR
DeLeo
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D016296:Mutagenesis; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000382:microbiology; D017384:Sequence Deletion; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D014157:Transcription Factors; D014774:Virulence
D001426:Bacterial Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D011494:Protein Kinases; C527351:SaeS protein, Staphylococcus aureus