Evolution of Plasmid-Mediated Antibiotic Resistance in the Clinical Context

• Published in: Trends in microbiology (Regular ed.) Vol. 26; no. 12; pp. 978 - 985
• Main Author: San Millan, Alvaro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2018
• Subjects: antibiotic resistance; clinical microbiology; evolutionary biology; gut microbiome; horizontal gene transfer; plasmid; plasmid; gut microbiome; evolutionary biology; clinical microbiology; antibiotic resistance; horizontal gene transfer
• ISSN: 0966-842X; 1878-4380
• DOI: 10.1016/j.tim.2018.06.007

Antibiotic-resistant infections are an urgent problem in clinical settings because they sharply increase mortality risk in critically ill patients. The horizontal spread of antibiotic resistance genes among bacteria is driven by bacterial plasmids, promoting the evolution of resistance. Crucially, particular associations exist between resistance plasmids and bacterial clones that become especially successful in clinical settings. However, the factors underlying the success of these associations remain unknown. Recent in vitro evidence reveals (i) that plasmids produce fitness costs in bacteria, and (ii) that these costs are alleviated over time through compensatory mutations. I argue that plasmid-imposed costs and subsequent compensatory adaptation may determine the success of associations between plasmids and bacteria in clinical settings, shaping the in vivo evolution of antibiotic resistance.
Antibiotic resistance (AR) in bacteria is one of the biggest threats currently facing humanity, and plasmids play an essential role in the dissemination of AR among clinically important pathogens.
Certain associations between AR plasmids and pathogenic bacterial clones are extremely prevalent.
In the absence of selection for plasmid-encoded traits, most plasmids reduce bacterial fitness. Recent in vitro findings demonstrate that this cost is alleviated by compensatory evolution. These evolutionary dynamics (cost versus compensation) determine the fate of the plasmid-carrying clone in the bacterial population.
The involvement of plasmid costs and compensatory evolution in the rise and spread of successful plasmid–bacterium associations in clinical contexts remains unexplored.