Fitness effects of antimicrobial resistance genes in changing environments
Hipolito, A.; Garcia-Pastor, L.; von Strempel, A.; Weiss, A. S.; Sastre-Dominguez, J.; Vergara, E.; Alvarez, J.; Fuentes-Hernandez, A.; Pena-Miller, R.; San Millan, A.; Stecher, B. S.; Escudero, J. A.
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The evolutionary success of antimicrobial resistance (AMR) genes is generally seen as a trade-off between their function in the presence and their cost in the absence of antibiotics. Mobile integrons are genetic elements that recruit and disseminate dozens of AMR genes among Gram-negative pathogens. Here, we have measured the fitness effects of 136 integron genes conferring resistance against several antibiotic families. We have found a significant proportion having neutral and positive effects in the absence of antibiotics. We confirmed this using a mouse model, where we also observed cases of changes in the sign of fitness effects. This led us to unveil that oxygen availability modulates the cost of AMR genes. Using a stochastic model, we show that fluctuating aerobic/anaerobic conditions can rescue AMR genes in the absence of selective pressure. Here we provide a comprehensive analysis of the cost of AMR at the gene level challenging the traditional fitness-resistance trade-off hypothesis.
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