[ Seminar ] The cost of antibiotic resistance in Escherichia coli

Title: The cost of antibiotic resistance in Escherichia coli

Speaker: Roberto Balbontín

Affiliation: Evolutionary Biology LaboratoryInstituto Gulbenkian de Ciência, Oeiras

Abstract:
Bacteria can become resistant to antibiotics by mutation of their 
protein targets, which are typically involved in essential 
physiological processes. Consequently, resistance mutations can cause 
a fitness cost in the absence of antibiotics, which is key for their 
maintenance and dissemination in bacterial populations. The cost of 
resistance mutations is influenced by the environment, and by genetic 
interactions with the background genome and/or other resistances 
(epistasis). Moreover, the cost can be alleviated by the acquisition 
of additional mutations that compensate for its deleterious effects. 
Recently, our lab described the existence of pervasive epistatic 
interactions among streptomycin (StrR) and Rifampicin (RifR) 
resistance mutations in Escherichia coli. By studying compensatory 
evolution of single and double StrR and RifR strains, we observed that 
compensatory evolution occurs faster in double resistant bacteria than 
in single resistant clones, and identified mutations that specifically 
compensate for the epistasis between resistances. Interestingly, 
compensation suggested that uncoupling between transcription and 
translation contributes to the costs of StrR and RifR resistances. We 
then analyzed downstream consequences of the uncoupling potentially 
causing the fitness cost of antibiotic resistance in a set of single 
and double resistant mutants. This revealed previously unknown 
processes responsible for the cost of resistance mutations, and 
provided a novel antimicrobial target, which we were able to validate 
using a repurposed drug. In summary, our results unveil major 
processes causing the fitness cost of resistance mutations and provide 
a novel target for antimicrobial therapies selective against resistant 
bacteria.