AI Insight
This study investigates the paradoxical observation that bacteria with more restriction-modification (RM) defense systems also tend to carry more mobile genetic elements, including antimicrobial resistance genes (ARGs). Using mathematical modeling and analysis of over 40,000 bacterial genomes, researchers found that eco-evolutionary feedbacks create positive associations between RM systems and horizontal gene transfer within species when RM diversity is low, while negative associations emerge across species when RM diversity is high. The findings reveal that increased exposure to mobile genetic elements drives stronger selection for RM systems, explaining why these defense mechanisms and resistance genes co-occur.
Why it matters
Understanding the relationship between bacterial defense systems and antimicrobial resistance gene acquisition could improve surveillance strategies by identifying bacterial strains at higher risk of acquiring new drug resistance through horizontal gene transfer. This knowledge may help predict and potentially prevent the spread of antibiotic resistance in pathogenic bacteria.
Understand the Science
by Joseph Westley, Paritosh Bedekar, Elizabeth Pursey, Mark D. Szczelkun, Mario Recker, Stineke van Houte, Edze R. Westra
Bacterial pathogens commonly become drug resistant via horizontal acquisition of antimicrobial resistance genes (ARGs), which are often encoded on mobile genetic elements (MGEs). Although bacterial defence systems are typically considered barriers to horizontal gene transfer (HGT), previous studies revealed that bacteria with more restriction-modification (RM) systems (the most abundant bacterial defences) frequently carry more MGEs. It was suggested that this counterintuitive relationship might result from stronger selection for RM systems when exposure to costly MGEs increases. Here, we test this hypothesis using a combination of modeling and bioinformatics analysis of >40,000 bacterial genomes to better understand how eco-evolutionary feedbacks between selection for RM and acquisition of MGEs shape bacterial genome evolution. Our model predicts negative associations between HGT and RM, but only if RM diversity is high. By contrast, at low RM diversity, eco-evolutionary feedbacks drive the emergence of positive associations between HGT and RM. Consistent with these predictions, we identified negative relationships between acquired ARG counts and RM counts across species but positive relationships within individual species. Collectively, our work helps to understand how RM systems shape patterns of HGT of ARGs, which may offer opportunities for targeted surveillance of strains at higher risk of horizontally acquiring novel drug resistance alleles.