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.

doi:10.64898/2026.03.06.710025

bioRxiv · 10.64898/2026.03.06.710025

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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Abstract

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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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.. 2026-03-06. Fitness effects of antimicrobial resistance genes in changing environments. https://doi.org/10.64898/2026.03.06.710025

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