Genomic determinants across cross- and co-resistance events of the environmental resistome of Klebsiellapneumoniae.

The emergence and spread of multidrug resistance (MDR) in Klebsiella pneumoniae are significantly influenced by environmental factors; yet, little is known about the full range of resistance gene diversity in environmental settings. In the present study, we characterized the resistome and co- and cross-selection dynamics of publicly available environmental K. pneumoniae genomes. We identified metal/biocide-resistant genes (MRGs/BRGs) and antibiotic-resistance genes (ARGs) in K. pneumoniae isolates. We then assessed co-resistance (occurrence of ARG-MRG/BRG pairs on the same plasmid) and cross-resistance (single proteins providing both ARG and MRG/BRG activity) mechanisms among identified ARGs and MRGs/BRGs. Our analysis shows that nearly all Klebsiella pneumoniae isolates harbor antimicrobial resistance genes (ARGs) against multiple drug classes, including β-lactams, fluoroquinolones, aminoglycosides, carbapenems, macrolides, and cephalosporins. The genomes also contain metal- and biocide-resistance genes (MRGs/BRGs) associated with tolerance to heavy metals such as iron, silver, copper, nickel, mercury, and tungsten, as well as biocides including triclosan, cetrimide, and benzalkonium chloride. Cross-resistance analysis reveals the association of ARGs with MRGs/BRGs in more than 95 % of K. pneumoniae genomes. In contrast, co-resistance analysis showed the association of ARGs with MRGs/BRGs in very few K. pneumoniae genome. The present study shows that environmental K. pneumoniae is a variable source of resistance factors influenced by chemical and metal compounds. This study underscores the relevance of environmental isolates that harbor extensive resistance determinants, emphasizing the importance of coordinated efforts across environmental and clinical domains to manage the spread of multidrug-resistant K. pneumoniae.