Genome-wide analysis of Burkholderia for the management of antimicrobial-resistant in cystic fibrosis patients.

Abstract

Burkholderia is a significant pathogen that causes disease burden across the globe. In particular, Burkholderia cenocepacia and Burkholderia multivorans are the predominant isolates that infect people with cystic fibrosis (CF) and cause hospital-acquired infections. Understanding antimicrobial resistance and virulent factors among these species is of great significance for addressing this growing resistance burden. Initially, we retrieved 75 complete genome sequences of B. cenocepacia and B. multivorans from NCBI database and analysed them for antimicrobial resistance (AMR) and virulent factors. This yielded 368 antimicrobial resistance genes and 202 virulent factors after removing the duplicates. Further, a comprehensive interaction network was constructed using STRING, which was visualized and analysed using Cytoscape. Through cytoHubba and MCODE analysis, eight key hub genes FliF, FliG, FliM, FliS, FlgB, FlgC, FlgD and FlgK were identified. Additionally, a non-homology analysis was conducted to ensure that the key nodes do not exhibit similarity with the human genome and gut microbiota. Functional enrichment analysis revealed their significant role in the flagellar assembly pathway, particularly in bacterial motility, colonization and biofilm formation. Notably, seven hub genes were enriched in bacterial-type flagellum-dependent cell motility pathway and cellular localization. It is worth noting that 17,967 phytochemicals were exploited to identify the potent hit compounds against each of the identified hub genes. Interestingly, the hit molecules were found to form several key interactions with the targets, indicating their potential as promising therapeutic agents for combating AMR. Overall, the identified hub genes and their potent inhibitors present compelling targets for novel antimicrobial therapies in CF, underscoring the need for future experimental validation.