Yin Wenjuan, Li Hui, Shen Yingbo, Liu Zhihai, Wang Shaolin, Shen Zhangqi, Zhang Rong, Walsh Timothy R, Shen Jianzhong, Wang Yang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China.
mBio. 2017 Jun 27;8(3):e00543-17. doi: 10.1128/mBio.00543-17.
The mobile colistin resistance gene has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of , and a second mobile colistin resistance gene, , have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine showed 45.0% and 47.0% nucleotide sequence identity to and , respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other species and in 10 species, respectively. pWJ1 was mobilized to an recipient by conjugation and contained a plasmid backbone similar to those of other -carrying plasmids, such as pHNSHP45-2 from the original -harboring strain. Moreover, a truncated transposon element, Tn, which was characterized only in , was located upstream of in pWJ1. This ΔTn- element was also identified in a shotgun genome sequence of a porcine isolate from Malaysia, a human isolate from Thailand, and a human serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene among and aeromonads; the latter may act as a potential reservoir for The emergence of the plasmid-mediated colistin resistance gene has attracted substantial attention worldwide. Here, we examined a colistin-resistant isolate that was negative for both and and discovered a novel mobile colistin resistance gene, The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from and species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of between and species, the wide spread of may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of genes in both the agricultural and health care sectors.
可移动的黏菌素耐药基因已引起全球关注,因为它预示着多黏菌素这一用于治疗由多重耐药革兰氏阴性菌引起的严重临床感染的最后一道抗生素防线被突破。迄今为止,在GenBank数据库中已报道或注释了六种略有不同的mcr-1变体,以及第二个可移动的黏菌素耐药基因mcr-2。在此,我们鉴定了第三个可移动的黏菌素耐药基因mcr-3。该基因与来自猪源大肠埃希菌的261-kb IncHI2型质粒pWJ1中的另外18个耐药决定簇共存,其核苷酸序列与mcr-1和mcr-2分别具有45.0%和47.0%的同一性,而MCR-3推导的氨基酸序列与在其他大肠埃希菌属物种和10个沙门氏菌属物种中发现的磷酸乙醇胺转移酶分别具有99.8%至100%和75.6%至94.8%的同一性。pWJ1通过接合转移至大肠杆菌受体菌,并且含有与其他携带mcr基因的质粒(如来自最初携带mcr-1的肺炎克雷伯菌菌株的pHNSHP45-2)相似的质粒骨架。此外,仅在mcr-1中鉴定到的截短转座子元件Tn6330位于pWJ1中mcr-3的上游。在来自马来西亚的猪源大肠埃希菌分离株、来自泰国的人源大肠埃希菌分离株和来自美国的人源鼠伤寒沙门氏菌分离株的鸟枪法基因组序列中也鉴定到了这个ΔTn6330元件。这些结果表明新型可移动黏菌素耐药基因mcr-3在大肠埃希菌属和气单胞菌属中广泛传播的可能性;后者可能是mcr-3的潜在储存库。质粒介导的黏菌素耐药基因mcr-1的出现已引起全球广泛关注。在此,我们检测了一株对mcr-1和mcr-2均呈阴性的黏菌素耐药大肠埃希菌分离株,并发现了一个新型可移动黏菌素耐药基因mcr-3。MCR-3的氨基酸序列与来自四大洲12个国家临床感染和环境样本中分离的大肠埃希菌属和沙门氏菌属物种的磷酸乙醇胺转移酶紧密比对。由于气单胞菌属在环境中无处不在,以及mcr基因在大肠埃希菌属和气单胞菌属物种之间可能发生转移,mcr-3的广泛传播可能被大大低估了。由于黏菌素过去和现在一直在兽医学中广泛使用,且在人类医学中的使用频率不断增加,持续监测耐黏菌素革兰氏阴性菌中的可移动黏菌素耐药决定簇对于了解和应对该基因在农业和医疗保健领域的传播至关重要。