Onderzoek naar genetische determinanten van persistentie in natuurlijke Escherichia coli isolaten met behulp van een genoomwijde associatiestudie

Bacterial adaptability enables survival across diverse environments, owning to evolutionary strategies, genetic flexibility, and robust survival mechanisms. Persistence, a transient, non-heritable state where subpopulations of bacteria endure antibiotic exposure without genetic resistance, presents significant public health challenges by contributing to chronic infections, treatment failures, and antibiotic resistance. This study investigated the genetic basis of bacterial persistence in 244 diverse Escherichia coli strains using a microbial genome-wide association study approach (GWAS). By quantifying persister levels against antibiotics (amikacin and ofloxacin), significant phenotypic variability was observed among strains. GWAS analysis identified several persistence-associated genetic variants, including known genes and novel candidates. Functional validation using gene deletion mutants revealed that these genes significantly influence persister survival. A detailed exploration of the hchA gene highlighted its role in mitigating reactive oxygen species (ROS) accumulation and protein aggregation during antibiotic stress, mechanisms critical for persister recovery. Strains lacking hchA exhibited heightened ROS damage and impaired persistence, emphasizing HchA's role in cellular resilience. These findings enhance our understanding of bacterial persistence mechanisms and identify novel targets for therapeutic intervention against antibiotic-tolerant infections.