AUTHOR=Wang Yanfei , Zhou Junxin , Liu Haiyang , Wang Qian , Zhang Ping , Zhu Jingyi , Zhao Dongdong , Wu Xueqing , Yu Yunsong , Jiang Yan 

TITLE=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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1122532

DOI=10.3389/fcimb.2023.1122532

ISSN=2235-2988

ABSTRACT=<p>Colistin and tigecycline are usually regarded as the last resort for multidrug-resistant <italic>Klebsiella pneumoniae</italic> 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 <italic>K. pneumoniae</italic> 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 (&gt; 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 <italic>mcr-1.1</italic>, <italic>mcr-8.2</italic> and <italic>crrB</italic> mutations are responsible for the high-level colistin resistance and that a series of efflux pump genes, such as <italic>tmexCD1-toprJ1</italic>, <italic>tet</italic>(A) and <italic>tet</italic>(M), contribute to tigecycline resistance. <italic>mcr-1.1</italic> and <italic>tet</italic>(M) are located on an IncX1 plasmid, which has conjugation transfer potential. <italic>mcr-8.2</italic> and <italic>tet</italic>(A) are located on a multireplicon IncR/IncN plasmid but unable to be transferred <italic>via</italic> conjugation. Moreover, another conjugable and fusion plasmid carries the <italic>tmexCD1-toprJ1</italic> gene cluster, which may have arisen due to IS<italic>26</italic>-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 <italic>mcr</italic>-carrying plasmids, combined with many other resistances, including tigecycline. Effective surveillance should be performed to prevent further dissemination.</p>