Biology subjects

Fuentes-Hernandez, A.

Publications and source records attributed to Fuentes-Hernandez, A..

3 recordsLinked to original sources

bioRxiv2026

Fitness effects of antimicrobial resistance genes in changing environments

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.

microbiology↗

bioRxiv2025

Plasmids promote antimicrobial resistance through Insertion Sequence-mediated gene inactivation

Antimicrobial Resistance (AMR) is a major threat to public health. Plasmids are mobile genetic elements that can rapidly spread across bacterial populations, promoting the dissemination of AMR genes in clinical bacteria. In addition, plasmids are enriched in insertion sequences (IS), which are small transposable elements able to translocate between genetic locations. Importantly, IS transpositions commonly lead to gene inactivation, which can in turn promote AMR (e.g. through the modification of the antibiotic target). In this study, we combined experimental, bioinformatic and computational approaches to investigate the role of plasmids as catalysts of AMR through IS-mediated gene inactivation. Our results revealed that plasmid pOXA-48, which encodes two IS1 elements, increases the rate of resistance acquisition to multiple antibiotics in clinical strains of Klebsiella pneumoniae through IS1-mediated gene disruption. Moreover, a large screen of genome databases confirmed that the inactivation of genes through plasmid-encoded IS elements is an extended mechanism of AMR evolution. Finally, both our experiments and computational model revealed that conjugative plasmids can promote this route of AMR acquisition while invading complex bacterial communities. Overall, our study reveals that conjugative plasmids fuel AMR not only through the dissemination of resistance genes, but also through IS-mediated gene inactivation, promoting the evolution of multidrug resistance in bacteria.

microbiology↗

bioRxiv2022

Antibiotic heteroresistance generated by multi-copy plasmids

Heteroresistance - in which a clonal bacterial population contains a cell subpopulation with higher resistance to antibiotics than the main population - is a growing clinical problem that complicates susceptibility determination and threatens therapeutic success. Despite the high prevalence of heteroresistance in clinical settings, the underlying genetic mechanisms that stably maintain heterogeneous bacterial populations are poorly understood. Using fluorescence microscopy, single-cell microfluidics, and quantitative image analysis, we show that random replication and segregation of multicopy plasmids produce populations of bacterium Escherichia coli MG1655 in which cells with low-and high-plasmid copy numbers stably co-exist. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression, we show that copy number variability confers the bacterial population with transient resistance to a lethal concentration of a {beta} -lactam antibiotic. Moreover, this surviving, high plasmid copy minority is capable of regenerating a heterogeneous bacterial population with low and high plasmid copy numbers through segregational instability, rapidly alleviating the fitness burden of carrying large numbers of plasmids. Our results provide further support for the tenet that plasmids are more than simple vehicles for horizontal transmission of genetic information between cells, as they can also drive bacterial adaptation in dynamic environments by providing a platform for rapid amplification and attenuation of gene copy number that can accelerate the rate of resistance adaptation and can lead to treatment failure.

microbiology↗