Abstract:
Carbapenem resistance\'s global proliferation poses a significant public health challenge. The primary resistance mechanism is carbapenemase production. In this study, we discovered a novel carbapenemase, RATA, located on the chromosome of Riemerella anatipestifer isolates. This enzyme shares ≤52 % amino acid sequence identity with other known β-lactamases. Antimicrobial susceptibility tests and kinetic assays demonstrated that RATA could hydrolyze not only penicillins and extended-spectrum cephalosporins but also monobactams, cephamycins, and carbapenems. Furthermore, its activity was readily inhibited by β-lactamase inhibitors. Bioinformatic analysis revealed 46 blaRATA-like genes encoding 27 variants in the NCBI database, involving 21 different species, including pathogens, host-associated bacteria, and environmental isolates. Notably, blaRATA-positive strains were globally distributed and primarily collected from marine environments. Concurrently, taxonomic analysis and GC content analysis indicated that blaRATA orthologue genes were predominantly located on the chromosomes of Flavobacteriaceae and shared a similar GC content as Flavobacteriaceae. Although no explicit mobile genetic elements were identified by genetic environment analysis, blaRATA-2 possessed the ability of horizontal transfer in R. anatipestifer via natural transformation. This work\'s data suggest that RATA is a new chromosome-encoded class A carbapenemase, and Flavobacteriaceae from marine environments could be the primary reservoir of the blaRATA gene.
摘要:
碳青霉烯类耐药的全球扩散构成了重大的公共卫生挑战。主要的抗性机制是碳青霉烯酶的产生。在这项研究中,我们发现了一种新的碳青霉烯酶,RATA,位于鼠尾草Riemerella分离株的染色体上。该酶与其他已知的β-内酰胺酶具有≤52%的氨基酸序列同一性。抗菌药物敏感性试验和动力学试验表明,RATA不仅可以水解青霉素和广谱头孢菌素,还可以水解单巴坦类药物。头霉素,和碳青霉烯类.此外,其活性容易被β-内酰胺酶抑制剂抑制。生物信息学分析显示,在NCBI数据库中,有46个blaRATA样基因编码27个变异体,涉及21个不同的物种,包括病原体,宿主相关细菌,和环境隔离物。值得注意的是,blaRATA阳性菌株分布在全球,主要从海洋环境中收集。同时,分类学分析和GC含量分析表明,blaRATA直向同源基因主要位于黄杆菌科的染色体上,并且具有与黄杆菌科相似的GC含量。虽然遗传环境分析没有发现明确的可移动遗传元件,blaRATA-2具有通过自然转化在R.anatipestifer中水平转移的能力。这项工作的数据表明,RATA是一种新的染色体编码的A类碳青霉烯酶,来自海洋环境的黄杆菌科可能是blaRATA基因的主要储层。