Whole-Genome Insights Into Tigecycline-Resistant <i>Klebsiella</i> Spp. Harboring Colistin Resistance Gene From Food Animals in Türkiye

Antimicrobial-resistant (AMR) <i>Klebsiella</i> spp., the common agents of nosocomial infections, are on the rise and becoming increasingly dangerous, with tigecycline-resistant strains posing a serious clinical threat. This study aimed to characterize isolated tigecycline-resistant strains from Türkiye by using whole-genome sequencing (WGS). The genomes of 40 strains, recovered from turkey caecum samples (<i>n</i> = 23, <i>K. pneumoniae</i>), chicken caecum samples (<i>n</i> = 8, <i>K. pneumoniae</i>; <i>n</i> = 2, <i>K. oxytoca</i>), and chicken meat samples (<i>n</i> = 7, <i>K. pneumoniae</i>), were determined. Additionally, Oxford Nanopore Sequencing was conducted on subsets (<i>mcr</i>-8-positive, <i>n</i> = 9) to characterize the plasmids responsible for colistin resistance spread. Sequence analysis revealed that all <i>K. pneumoniae</i> harbored the <i>tet</i>(A) gene without detectable mutations, whereas several alterations were detected in the <i>ramR</i> gene. Additionally, other tetracycline-encoding genes were also detected in few isolates, including <i>tet</i>(B), <i>tet</i>(D), <i>tet</i>(J), and <i>tet</i>(M). Genomic analysis revealed various AMR genes, including the plasmid-mediated colistin resistance gene <i>mcr</i>-8, for which hybrid assemblies confirmed the localization on IncF group plasmids associated with IS<i>903B</i>. Conjugation assay showed the transferability of <i>mcr</i>-8 in isolates (8/9) to <i>Escherichia coli</i> recipient strains. WGS analysis also revealed 11 different sequence types (STs), with ST37 appearing as the predominant lineage among both tigecycline- and colistin-resistant isolates. Phylogenetic comparison with previously sequenced isolates showed close genetic relatedness between certain isolates and international clones. To our knowledge, this is the first report of <i>mcr</i>-8 in <i>Klebsiella</i> strains from food animals in Türkiye, highlighting a potential risk for transmission of last-resort antimicrobial resistance genes to humans. Hence, continuous genomic surveillance is urgently needed to monitor the spread of these resistance determinants within the One Health perspective.