Losa-Mediavilla, C. | bioRxiv Science

bioRxiv2026

Genetic context drives evolution of divergent antibiotic survival phenotypes in Staphylococcus epidermidis

Effective treatment of infections is a global challenge, complicated by bacterias capacity to endure antibiotics. Survival under drug pressure is often driven by interactions between genetic factors rather than single genes. To investigate the genomics underlying antibiotic survival, we analysed Staphylococcus epidermidis isolates from clinical infections and carriage using high-throughput phenotyping, population genomics, and directed evolution. We observed widespread multidrug resistance, with strong links between specific genomic elements and resistance. All isolates harbouring mecA were resistant to oxacillin, though minimum inhibitory concentrations varied significantly, suggesting modulation by additional genetic factors. Directed evolution revealed potentiating mutations that enhanced oxacillin resistance in mecA+ strains. In mecA-isolates, however, evolution of mutations in the same genes conferred increased survival to oxacillin through antibiotic tolerance. These findings show that antibiotic resistance and tolerance can be genetically connected yet phenotypically distinct, and suggest a complex epistatic genetic landscape that shapes antibiotic survival phenotypes in S. epidermidis.

microbiology↗

bioRxiv2024

Assessing the role of bacterial innate and adaptive immunity as barriers to conjugative plasmids

Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (RM) (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that RM and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the adaptive advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist for a certain period in the bacterial population, RM and CRISPR-Cas pose a substantial burden for such plasmids, which can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face substantial reduction in prevalence or even extinction.

microbiology↗