title: Role of hypermutability on bacterial fitness and emergence of resistance in experimental osteomyelitis due to Staphylococcus aureus.
abstract: This study was designed to investigate the role of hypermutability of Staphylococcus aureus on bacterial fitness and antibiotic resistance in a model of chronic bone infection. An isogenic pair of strains, S. aureus RN4220 and its mutator counterpart inactivated in the mutL gene were used in a rat model of osteomyelitis of the tibia. The effect of the mutator phenotype in the emergence of antibiotic resistance was assessed in rats infected by each strain separately and treated with rifampicin for 5 days. No difference between the two strains was found in bacterial growth in vitro and in bacterial survival in the animal model, indicating no fitness defect in the mutator strain. In competition studies performed in rats coinfected with the two strains at a same ratio and sacrificed at different times from day 3 to day 42 postinoculation, the mutator strain was clearly disadvantaged because it was found in all rats and at all study times at lower counts (P<0.05 from day 14 to day 42). Two of the 16 rats infected by the mutator strain and none of the 14 rats infected by the wild-type strain had acquired rifampicin-resistant mutants (P=0.4). Data suggest that the S. aureus mutator phenotype was associated with a decreased bacterial fitness in vivo and did not confer significant advantage in the acquisition of antibiotic resistance in a model of chronic bone infection.
authors: EA 3964, Faculté de Médecine, Université Paris 7 Denis Diderot, Paris, Cedex, France.
authors: Claire
authors: C
authors: Daurel
authors: Anne-Laure
authors: AL
authors: Prunier
authors: Françoise
authors: F
authors: Chau
authors: Louis
authors: L
authors: Garry
authors: Roland
authors: R
authors: Leclercq
authors: Bruno
authors: B
authors: Fantin
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001842:Bone and Bones / Q000382:microbiology; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional; D010019:Osteomyelitis / Q000188:drug therapy / Q000382:microbiology*; D051381:Rats; D012293:Rifampin / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D016019:Survival Analysis
chemical_list: D001426:Bacterial Proteins; D000251:Adenosine Triphosphatases; D012293:Rifampin