The rapid global dissemination of multidrug-resistant Acinetobacter baumannii poses a critical threat to public health, yet the role of the Type VI Secretion System (T6SS)-a contact-dependent interbacterial weapon-in shaping the antimicrobial resistome remains poorly understood. Here, we integrated clinical metagenomics and large-scale comparative genomics to investigate the association between T6SS completeness and resistome organization. T6SS status was not independently associated with overall antimicrobial resistance genes (ARGs) burden or alpha diversity after controlling for shared evolutionary history and genomic background. However, T6SS completeness was associated with distinct resistome composition across multiple lineages. T6SS-complete genomes were preferentially enriched in chromosomally associated resistance determinants, including intrinsic beta-lactamases and multidrug efflux systems, alongside tighter genomic co-localization between ARGs and mobile genetic elements (MGEs), consistent with localized chromosomal integration of resistance-associated mobile elements. This foundational prerequisite was supported by experimental validation of efficient T6SS-dependent interbacterial killing in a hyper-resistant lineage. Conversely, T6SS-incomplete genomes were significantly enriched in highly potent exogenously acquired ARGs, including blaNDM-1 and blaCTX-M, frequently alongside structurally uncoupled MGEs. Together, these findings are consistent with an evolutionary trade-off model in which T6SS-complete and T6SS-incomplete A. baumannii populations exhibit distinct resistance acquisition strategies and contrasting genomic contexts of horizontal gene transfer, thereby contributing to divergent resistome organization.
[1]First Hosp Jilin Univ, Ctr Pathogen Biol & Infect Dis, Dept Resp Med, State Key Lab Diag & Treatment Severe Zoonot Infec, Changchun, Peoples R China.
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