title: Ribonucleotide reductase class III, an essential enzyme for the anaerobic growth of Staphylococcus aureus, is a virulence determinant in septic arthritis.
abstract: Staphylococcus aureus is the most common cause of joint infections. It also contributes to several other diseases such as pneumonia, osteomyelitis, endocarditis, and sepsis. Bearing in mind that S. aureus becomes rapidly resistant to new antibiotics, many studies survey the virulence factors, with the aim to find alternative prophylaxis/treatment regimens. One potential virulence factor is the bacterial ability to survive at different oxygen tensions. S. aureus expresses ribonucleotide reductases (RNRs), which help it to grow under both aerobic and anaerobic conditions, by reducing ribonucleotides to deoxyribonucleotides. In this study, we investigated the role of RNR class III, which is required for anaerobic growth, as a virulence determinant in the pathogenesis of staphylococcal arthritis. The wild-type S. aureus strain and its isogenic mutant nrdDG mutant were inoculated intravenously into mice. Mice inoculated with the wild-type strain displayed significantly more severe arthritis, with significantly more synovitis and destruction of the bone and cartilage versus mutant strain inoculated mice. Further, the persistence of bacteria in the kidneys was significantly more pronounced in the group inoculated with the wild-type strain. Together these results indicate that RNR class III is an important virulence factor for the establishment of septic arthritis.
authors.affiliation: Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10A, S-413 46 Göteborg, Sweden.
authors.forename: Ebru
authors.initials: E
authors.lastname: Kirdis
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kubica
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.forename: Mahmud
authors.initials: M
authors.lastname: Masalha
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tarkowski
mesh_terms: D000332:Aerobiosis; D000818:Animals; D001170:Arthritis, Infectious / Q000382:microbiology* / Q000473:pathology; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000382:microbiology; D051379:Mice; D012264:Ribonucleotide Reductases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
chemical_list: D012264:Ribonucleotide Reductases