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Persistence of a Staphylococcus aureus small-colony variant under antibiotic pressure in vivo
Eric Brouillette1, Alejandro Martinez, Bobbi J Boyll
1Centre d'Etude et de Valorisation de la Diversité Microbienne (CEVDM), Département de biologie, Université de Sherbrooke, Sherbrooke, Que., Canada J1K 2R1.
Abstract:
Staphylococcus aureus small-colony variants (SCVs) have been implicated in chronic and persistent infections. Bovine mastitis induced by S. aureus is an example of an infection difficult to eradicate by conventional antimicrobial therapies. In this study, the ability to colonize mouse mammary glands and persist under antibiotic treatment was assessed for S. aureus Newbould and an isogenic hemB mutant, which exhibited the classical SCV phenotype. The hemB mutant showed a markedly reduced capacity to colonize tissues. However, although the hemB mutant was as susceptible as S. aureus Newbould to cephapirin in vitro, it was over a 100 times more persistent than the parental strain in the mammary glands when 1 or 2 mg kg(-1) doses were administrated. These results suggest that, although the hemB mutant has a reduced ability to colonize mammary glands, the SCV phenotype may account for the persistence of S. aureus under antibiotic pressure in vivo.
Insights
Staphylococcus aureus small-colony variants (SCVs) show reduced colonization but increased persistence in mouse mammary glands during antibiotic treatment. The SCV phenotype may explain persistent S. aureus infections despite antimicrobial therapy.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Staphylococcus aureus small-colony variants (SCVs) are linked to persistent infections.
- Bovine mastitis caused by S. aureus is challenging to treat with standard antibiotics.
Purpose of the Study:
- To evaluate the colonization and persistence of S. aureus Newbould and its hemB mutant (SCV phenotype) in mouse mammary glands under antibiotic pressure.
- To understand the role of the SCV phenotype in S. aureus persistence during antimicrobial therapy.
Main Methods:
- Comparison of S. aureus Newbould and an isogenic hemB mutant (SCV) in a mouse mammary gland colonization model.
- Assessment of bacterial persistence following administration of cephapirin at 1 or 2 mg kg(-1).
- In vitro susceptibility testing of both strains to cephapirin.
Main Results:
- The hemB mutant exhibited significantly reduced tissue colonization compared to the parental strain.
- In vitro, the hemB mutant showed similar susceptibility to cephapirin as S. aureus Newbould.
- Despite reduced colonization, the hemB mutant was over 100 times more persistent in mammary glands than the parental strain under antibiotic treatment.
Conclusions:
- The SCV phenotype in S. aureus, while impairing initial colonization, enhances bacterial persistence in mammary glands during antibiotic treatment.
- The SCV phenotype may be a key factor in the in vivo persistence of S. aureus under antimicrobial pressure.
- These findings offer insights into the mechanisms behind chronic and difficult-to-eradicate S. aureus infections.
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