The vir Locus Affects the Response of Bordetella pertussis to Antibiotics: Phenotypic Tolerance and Control of Autolysis

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Abstract
Eradication of Bordetella pertussis from the respiratory tract occurs slowly even when bactericidal antibiotics are used. The rate of killing of B. pertussis was found to be proportional to growth rate: virulent, slowly growing strains were killed over days, while rapidly growing strains (either avirulent or virulent modulated by growth conditions to avirulent) were killed over hours. Minimum inhibitory concentrations and binding of antibiotics-to membrane targets were equivalent in virulent and avirulent cells, suggesting differences in antibiotic response might reflect differences in activities ofthe autolytic cascade. This was supported by the finding that cell wall degradation was 70% per day in avirulent strains. Penem antibiotics, known to rapidly kill even slowly growing bacteria, demonstrated a more-than-twofold greater rate of killing ofslowly growing virulent strains compared with ampicillin or erythromycin. This suggests the potential for improved therapeutic efficacy in vivo. Thus, the vir locus, which determines phase transition in B. pertussis, is apparently the first example of a sensortransducer system controlling phenotypic tolerance and antibiotic-induced autolytic activity.