title: Role of the accessory gene regulator (agr) in pathogenesis of staphylococcal osteomyelitis.
abstract: To examine the role of the accessory gene regulator (agr) in staphylococcal osteomyelitis, we compared a Staphylococcus aureus osteomyelitis isolate (UAMS-1) with a derivative of the same strain (UAMS-4) carrying an inactivated agr locus. Virulence was assessed with a rabbit model of acute, exogenous osteomyelitis. Bacteria were delivered by microinjection into the midradial region of the forelimb. After 4 weeks, UAMS-1 was identified in the bone of 12 of 13 rabbits infected with > or = 2 x 10(6) CFU and 5 of 6 infected with < or = 2 x 10(5) CFU. In contrast, UAMS-4 was found in 6 of 13 infected with the higher dose and 1 of 6 infected with the lower dose. Additionally, on the basis of a five-point scale assessing radiographic evidence of disease, rabbits infected with UAMS-1 had average scores of 2.64 +/- 0.30 (high dose) and 1.43 +/- 0.39 (low dose) while rabbits infected with UAMS-4 had average scores of 0.95 +/- 0.23 (high dose) and 0.63 +/- 0.20 (low dose). Uninfected controls had an average score of 0.53 +/- 0.08. The results obtained with UAMS-1 were significantly different from those obtained with UAMS-4 at both doses (P < or = 0.047). The results obtained with UAMS-4 were not significantly different from those obtained with the controls at either dose of UAMS-4 (P > or = 0.150). On the basis of a similar five-point scale assessing histopathological evidence of disease, rabbits infected with UAMS-1 had average scores of 2.31 +/- 0.22 (high dose) and 1.96 +/- 0.36 (low dose) while rabbits infected with UAMS-4 had average scores of 1.58 +/- 0.29 (high dose) and 0.83 +/- 0.32 (low dose). Controls had an average score of 0.33 +/- 0.05. The results obtained with UAMS-1 were significantly different from those obtained with UAMS-4 at both doses (P < or = 0.040). However, the results obtained with UAMS-4 were significantly different from the controls only at the high dose of UAMS-4 (P = 0.025). We conclude that mutation of agr reduces the incidence and severity of disease but does not eliminate the ability to colonize bone and cause histopathological evidence of osteomyelitis.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Gillaspy
authors.forename: S G
authors.initials: SG
authors.lastname: Hickmon
authors.forename: R A
authors.initials: RA
authors.lastname: Skinner
authors.forename: J R
authors.initials: JR
authors.lastname: Thomas
authors.forename: C L
authors.initials: CL
authors.lastname: Nelson
authors.forename: M S
authors.initials: MS
authors.lastname: Smeltzer
mesh_terms: D000818:Animals; D005798:Genes, Bacterial; D005809:Genes, Regulator; D006801:Humans; D008297:Male; D010019:Osteomyelitis / Q000209:etiology*; D011817:Rabbits; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000209:etiology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence