The biological cost of resistance to antibiotics

University dissertation from Uppsala : Acta Universitatis Upsaliensis

Abstract: The rate of development and stability of antibiotic resistance are determined by several factors including (i) the mutation rate, (ii) the fitness costs of resistance, and (iii) the ability of bacteria to genetically compensate for such costs.. This study has focused on the experimental measurement of these parameters in antibiotic-resistant S. typhimurium and S. aureus strains during growth within and outside the host.Most of the S. typhimurium and S. aureus strains that are antibiotic resistant by virtue of chromosomally encoded target alterations were avirulent compared to sensitive bacteria. During growth in an antibiotic-free environment, the avirulent resistant bacteria could rapidly accumulate compensatory mutations that restored fitness without concomitant loss of resistance. Different fitness-compensating mutations were shown to be selected in S. typhimurium and S. aureus depending on whether the bacteria evolved within or outside the host. This difference was either caused by a growth condition-specific formation or selection of the compensated mutants. The bacterial mutation frequency appeared to be higher for bacteria grown in mice than bacteria grown in laboratory medium.Because of compensatory evolution and the maintenance of resistance in thecompensated clones, a reduction in the use of antibiotics might not result in the disappearance of the resistant bacteria already present in human and environmental reservoirs.

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