Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance. Issue 8 (August 2018)

• Record Type: Journal Article
• Authors: Durão, Paulo; Balbontín, Roberto; Gordo, Isabel
• Is Part Of: Trends in microbiology. Volume 26:Issue 8(2018)
• Page Start: 677
• Page End: 691
• Publication Date: 2018-08
• Subjects: antibiotic -- evolution -- fitness costs -- compensation -- epistasis -- multidrug resistance; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2018.01.005
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : Antibiotics target essential cellular functions but bacteria can become resistant by acquiring either exogenous resistance genes or chromosomal mutations. Resistance mutations typically occur in genes encoding essential functions; these mutations are therefore generally detrimental in the absence of drugs. However, bacteria can reduce this handicap by acquiring additional mutations, known as compensatory mutations. Genetic interactions (epistasis) either with the background or between resistances (in multiresistant bacteria) dramatically affect the fitness cost of antibiotic resistance and its compensation, therefore shaping dissemination of antibiotic resistance mutations. This Review summarizes current knowledge on the evolutionary mechanisms influencing maintenance of resistance mediated by chromosomal mutations, focusing on their fitness cost, compensatory evolution, epistasis, and the effect of the environment on these processes. Highlights: Most antibiotic resistance mutations reduce bacterial fitness in the absence of the antibiotic, but some are not costly, or can even be advantageous in certain environments, including infection-related conditions. Acquiring a new resistance can alleviate the cost of a pre-existing one, thus favouring the emergence of multidrug-resistant bacteria. The compensatory evolution of multidrug-resistant bacteria is distinct from that of single-resistant bacteria, since the proteins mediating functional interactions between those affected by resistance mutations become new targets for their compensation.