College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510641, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
Genomics Proteomics Bioinformatics. 2022 Dec;20(6):1168-1179. doi: 10.1016/j.gpb.2022.11.006. Epub 2022 Dec 5.
Emergence of the colistin resistance gene, mcr-1, has attracted worldwide attention. Despite the prevalence of mcr-1-positive Escherichia coli (MCRPEC) strains in human carriage showing a significant decrease between 2016 and 2019, genetic differences in MCRPEC strains remain largely unknown. We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019. We identified three major differences in MCRPEC strains between these two time points. First, the insertion sequence ISApl1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019. Second, the antibiotic resistance genes (ARGs), aac(3)-IVa and bla, emerged and coexisted with mcr-1 in 2019. Third, MCRPEC strains in 2019 contained more virulence genes, resulting in an increased proportion of extraintestinal pathogenic E. coli (ExPEC) strains (36.1%) in MCRPEC strains in 2019 compared to that in 2016 (10.5%), implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria. Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019, MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes, which may pose a potential public health threat.
粘菌素耐药基因 mcr-1 的出现引起了全球关注。尽管 2016 年至 2019 年间，人携带的 mcr-1 阳性大肠杆菌（MCRPEC）菌株的流行率显著下降，但 MCRPEC 菌株的遗传差异在很大程度上仍不清楚。因此，我们对 2016 年和 2019 年健康人体粪便样本中的 MCRPEC 菌株进行了比较基因组学研究。我们发现这两个时间点的 MCRPEC 菌株有三个主要差异。首先，2019 年 MCRPEC 菌株中插入序列 ISApl1 经常缺失，携带 mcr-1 的 IncI2 质粒的比例增加。其次，2019 年出现了抗生素耐药基因（ARGs）aac(3)-IVa 和 bla，与 mcr-1 共存。第三，2019 年 MCRPEC 菌株携带更多的毒力基因，导致 2019 年 MCRPEC 菌株中外周型肠致病性大肠杆菌（ExPEC）菌株的比例（36.1%）高于 2016 年（10.5%），这意味着这些菌株可以通过与其他共生菌竞争来占据肠道生态位。我们的研究结果表明，尽管 2016 年至 2019 年，人携带的 MCRPEC 菌株的流行率显著下降，但 MCRPEC 对其他临床上重要的 ARGs 的耐药性增加，并且携带更多的毒力基因，这可能对公共卫生构成潜在威胁。
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