Pharmacodynamics, population dynamics, and the evolution of persistence in Staphylococcus aureus

PLoS Genetics
Paul J T Johnson, Bruce R Levin

Abstract

When growing populations of bacteria are confronted with bactericidal antibiotics, the vast majority of cells are killed, but subpopulations of genetically susceptible but phenotypically resistant bacteria survive. In accord with the prevailing view, these "persisters" are non- or slowly dividing cells randomly generated from the dominant population. Antibiotics enrich populations for pre-existing persisters but play no role in their generation. The results of recent studies with Escherichia coli suggest that at least one antibiotic, ciprofloxacin, can contribute to the generation of persisters. To more generally elucidate the role of antibiotics in the generation of and selection for persisters and the nature of persistence in general, we use mathematical models and experiments with Staphylococcus aureus (Newman) and the antibiotics ciprofloxacin, gentamicin, vancomycin, and oxacillin. Our results indicate that the level of persistence varies among these drugs and their concentrations, and there is considerable variation in this level among independent cultures and mixtures of independent cultures. A model that assumes that the rate of production of persisters is low and persisters grow slowly in the presence of antibiotics ca...Continue Reading

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Related Concepts

Antibiotics
Biological Evolution
Neomalthusianism
Selection, Genetic
Staphylococcal Infections
Staphylococcus aureus
Antibiotic Resistance, Bacterial
Bactericide, NOS
Cell Division
Ciprofloxacin

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