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.
Voyich
Jovanka M
JM
Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA. jovanka@montana.edu
Vuong
Cuong
C
DeWald
Mark
M
Nygaard
Tyler K
TK
Kocianova
Stanislava
S
Griffith
Shannon
S
Jones
Jennifer
J
Iverson
Courtney
C
Sturdevant
Daniel E
DE
Braughton
Kevin R
KR
Whitney
Adeline R
AR
Otto
Michael
M
DeLeo
Frank R
FR
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