Emergence of high-level colistin resistance mediated by multiple determinants, including mcr-1.1, mcr-8.2 and crrB mutations, combined with tigecycline resistance in an ST656 Klebsiella pneumoniae
Frontiers in Cellular and Infection Microbiology(2023)
摘要
Colistin and tigecycline are usually regarded as the last resort for multidrug-resistant Klebsiella pneumoniae infection treatment. Emergence of colistin and tigecycline resistance poses a global healthcare challenge and is associated with high mortality due to limited therapeutic options. Here, we report the ST656 extensively drug-resistant K. pneumoniae strain KP15-652, which was isolated from a patient’s urine in China. Antimicrobial susceptibility testing showed it to be resistant to tigecycline, amikacin, levofloxacin, ciprofloxacin, and high-level colistin resistance (> 2048 mg/L). Whole-genome sequencing revealed that it harbors one chromosome and seven plasmids, including four plasmids carrying multiple acquired resistance genes. Transformation/conjugation tests and plasmid curing assays confirmed that mcr-1.1, mcr-8.2 and crrB mutations are responsible for the high-level colistin resistance and that a series of efflux pump genes, such as tmexCD1-toprJ1, tet(A) and tet(M), contribute to tigecycline resistance. mcr-1.1 and tet(M) are located on an IncX1 plasmid, which has conjugation transfer potential. mcr-8.2 and tet(A) are located on a multireplicon IncR/IncN plasmid but unable to be transferred via conjugation. Moreover, another conjugable and fusion plasmid carries the tmexCD1-toprJ1 gene cluster, which may have arisen due to IS26-mediated replicative transposition based on 8-bp target-site duplications. Importantly, a complex class 1 integron carrying various resistance genes was detected on this fusion plasmid. In conclusion, it is possible that the high-level of colistin resistance is caused by the accumulated effect of several factors on the chromosome and mcr-carrying plasmids, combined with many other resistances, including tigecycline. Effective surveillance should be performed to prevent further dissemination.
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关键词
colistin,mcr,tigecycline,tmexCD1-toprJ1,co-integration
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