Zhang Baoyue, Yu Bing, Zhou Wei, Wang Yue, Sun Ziyong, Wu Xiaojun, Chen Shiyun, Ni Ming, Hu Yangbo
CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Microbiol. 2021 Feb 15;12:619369. doi: 10.3389/fmicb.2021.619369. eCollection 2021.
Multidrug-resistant bacteria, including carbapenem-resistant (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as "the last treatment option." In this study, we isolated a clinical CRKP strain named as R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS family IS element into the colistin-resistance associated gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of IS containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of IS could be inserted into the gene to cause colistin-resistance, though the plasmid-derived IS without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive strain transferred with the IS element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the IS-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.
包括耐碳青霉烯类肺炎克雷伯菌（CRKP）在内的多重耐药菌，正成为全球日益严重的健康危机。对于CRKP而言，黏菌素被视为“最后的治疗选择”。在本研究中，我们分离出一株临床CRKP菌株，命名为R10 - 341。表型分析表明，该菌株可通过将一个IS家族的IS元件插入与黏菌素耐药相关的基因，从黏菌素敏感表型转变为耐药表型。为探究这种转变的机制，我们对黏菌素敏感的亲代菌株进行了全基因组测序分析，发现12个含有正向重复序列（DR）的IS拷贝位于染色体上，1个不含DR的拷贝位于多重耐药质粒pR10 - 341_2上。这两种类型的IS均可插入该基因导致黏菌素耐药，尽管来自质粒的不含DR的IS效率更高。重要的是，我们证明携带IS元件的黏菌素敏感菌株也获得了从黏菌素敏感转变为黏菌素耐药表型的能力。此外，我们证实含有IS的pR10 - 341_2质粒能够接合，这表明导致黏菌素耐药转变的能力可通过常见的接合作用进行转移。我们的研究结果为黏菌素耐药性检测和CRKP治疗带来了新的挑战。
