Sigma factor B and RsbU are required for virulence in Staphylococcus aureus-induced arthritis and sepsis.
The prototype Staphylococcus aureus strain 8325-4 produces high levels of hemolysins and proteases. Recently it has been shown that this property depends on a deficiency of sigma factor B (SigB) activity controlling the activation of regulatory genes such as agr and sarA. SigB deficiency is in turn due to a mutation in the rsbU gene, which is required for posttranslational activation of SigB. The rsbU defect of strain 8325-4 has recently been repaired, and we used this strain (SH1000), along with its isogenic sigB-negative mutant, to investigate the contributions of RsbU and SigB in a murine model of septic arthritis. Intravenous inoculation with the rsbU-repaired isogenic strain SH1000 resulted in significantly more severe arthritis, weight decrease, and mortality compared to those of the parental strain 8325-4 (rsbU-negative) or the isogenic sigB-negative mutant (MJH502). SH1000 also persisted more in kidneys and joints of infected mice. Our data strongly suggest that RsbU and SigB regulate important virulence factors, thereby contributing significantly to the outcome of staphylococcal infection.
Jonsson
Ing-Marie
IM
Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden. ing-marie.jonsson@rheuma.gu.se
Arvidson
Staffan
S
Foster
Simon
S
Tarkowski
Andrzej
A
D000818:Animals; D001168:Arthritis / Q000097:blood / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D001426:Bacterial Proteins / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000276:immunology / Q000382:microbiology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007668:Kidney / Q000382:microbiology; D007719:Knee Joint / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D012808:Sigma Factor / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000097:blood / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity*; D013997:Time Factors; D014774:Virulence
D001426:Bacterial Proteins; D015850:Interleukin-6; C079011:SigB protein, Bacteria; D012808:Sigma Factor