Journal of Global Antimicrobial Resistance (Dec 2024)
Unravelling resistance in Burkholderia cenocepacia: Multi-omic insights into genetic and transcriptomic adaptations to sub-inhibitory antibiotic stress
Abstract
AIM: To elucidate the molecular mechanisms driving the resistance phenotype of (Burkholderia cenocepacia under sub-inhibitory antibiotic stress BACKGROUND: The Burkholderia cepacia complex (BCC) includes 20 species of non-fermenting gram-negative bacteria. BCC is a major hospital-associated pathogen, causing severe infections and exhibiting intrinsic antibiotic resistance. Understanding how Bcc adapts and responds to antibiotic therapy is crucial for shaping future therapeutic and stewardship strategies. METHODS: We methodically analysed ceftazidime-resistant and -sensitive (Burkholderia cenocepacia isolates. RNA expression profiles were examined under in vitro sub-inhibitory conditions. By integrating phenotypic, genomic, and transcriptomic assessments, we aimed to elucidate the key mechanisms driving the survival of resistant isolates under sub-inhibitory conditions. RESULT: The study highlights that ceftazidime-resistant (Burkholderia cenocepacia isolate possesses a greater total gene count but fewer resistance genes compared to the sensitive. Under sub-inhibitory conditions, the resistant isolate showed enhanced growth and upregulated genes involved in carbohydrate metabolism, stress response, and biofilm formation. Resistance mechanisms included significant upregulation of multidrug efflux pumps and virulence factors, highlighting increased survival and pathogenicity. Gene set enrichment and differential expression analyses further underscore the adaptive strategies and virulence enhancement of the resistant isolate under antibiotic stress. CONCLUSION: Study highlights genetic factors and sub-inhibitory antibiotic concentrations influence the resistance phenotype of (Burkholderia cenocepacia. The upregulation of multidrug efflux pumps and stress response genes underscores the pathogen's adaptive strategies. The study underscores the value of multi-omic integration in guiding the development of future treatment and management approaches
