Liu Haiyang, Liu Xiaochen, He Jintao, Zhang Linghong, Zhao Feng, Zhou Zhihui, Hua Xiaoting, Yu Yunsong
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou 310016, China.
Antibiotics (Basel). 2023 Feb 16;12(2):396. doi: 10.3390/antibiotics12020396.
Carbapenem-resistant (CRAB) isolates of global clone 1 (GC1) and global clone 2 (GC2) have been widely reported. Nevertheless, non-GC1 and non-GC2 CRAB strains have been studied less. In particular, no reports concerning sequence type 46 (ST46) CRAB strains have been described thus far. In this work, the genomic features and possible evolution mechanism of ST46 OXA-23-producing CRAB isolates from clinical specimens are reported for the first time. Antimicrobial susceptibility testing of three ST46 strains revealed identical resistance profiles (resistance to imipenem, meropenem, ciprofloxacin and the combination of cefoperazone/sulbactam at a 2:1 ratio). They were found to belong to ST46 and ST462 with capsular polysaccharide 28 (KL28) and lipooligosaccharide 1 (OCL1), respectively. Whole-genome sequencing (WGS) revealed that all contained one copy of chromosomal , which was located in a novel IS-based Tn composite transposon. In particular, another copy of the Tn composite transposon was identified in an Hgz_103-type plasmid with 9 bp target site duplications (TSDs, ACAACATGC) in the ZHOU strain. As the strains originated from two neighboring intensive care units (ICUs), ST46 OXA-23-producing CRAB strains may have evolved via transposition events or a p module. Based on the GenBank database, ST46 strains were collected from various sources; however, most were collected in Hangzhou (China) from 2014 to 2021. Pan-genome analysis revealed 3276 core genes, 0 soft-core genes, 768 shell genes and 443 cloud genes shared among all ST46 strains. In conclusion, the emergence of ST46 CRAB strains might present a new threat to healthcare settings; therefore, effective surveillance is required to prevent further dissemination.
全球克隆1（GC1）和全球克隆2（GC2）的耐碳青霉烯类（CRAB）分离株已被广泛报道。然而，非GC1和非GC2的CRAB菌株研究较少。特别是，迄今为止尚未有关于序列类型46（ST46）CRAB菌株的报道。在这项工作中，首次报道了来自临床标本的产OXA-23的ST46 CRAB分离株的基因组特征和可能的进化机制。对三株ST46菌株进行的药敏试验显示出相同的耐药谱（对亚胺培南、美罗培南、环丙沙星以及2:1比例的头孢哌酮/舒巴坦联合用药耐药）。发现它们分别属于带有荚膜多糖28（KL28）的ST46和带有脂寡糖1（OCL1）的ST462。全基因组测序（WGS）显示，所有菌株均含有一个位于新型基于插入序列的Tn复合转座子中的染色体拷贝。特别是，在周菌株的一个Hgz_103型质粒中鉴定出另一个Tn复合转座子拷贝，其具有9 bp的靶位点重复序列（TSD，ACAACATGC）。由于这些菌株源自两个相邻的重症监护病房（ICU），产OXA-23的ST46 CRAB菌株可能是通过转座事件或p模块进化而来。基于GenBank数据库，ST46菌株从各种来源收集；然而，大多数是2014年至2021年在中国杭州收集的。泛基因组分析显示，所有ST46菌株共有3276个核心基因、0个软核心基因、768个外壳基因和443个云基因。总之，ST46 CRAB菌株的出现可能对医疗机构构成新的威胁；因此，需要进行有效的监测以防止其进一步传播。
