Abstract:
The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven by metallo-β-lactamases (MBLs), which can catalyse the hydrolysis of almost all clinically available β-lactams and are resistant to all the clinically utilized β-lactamase inhibitors. In this study, an uncharacterized MBL is identified in a multidrug resistant isolate of the opportunistic pathogen, Chryseobacterium indologenes. Sequence analysis predicts this MBL (CIM-1) to be a lipoprotein with an atypical lipobox. Characterization of CIM-1 reveals it to be a high-affinity carbapenemase with a broad spectrum of activity that includes all cephalosporins and carbapenems. Results also shown that CIM-1 is potentially a membrane-associated MBL with an uncharacterized lipobox. Using prediction tools, we also identify more potentially lipidated MBLs with non-canonical lipoboxes highlighting the necessity of further investigation of lipidated MBLs.
摘要:
医疗保健环境中耐碳青霉烯细菌的增加速率是一个需要紧急关注的问题。这种抗性是由金属-β-内酰胺酶(MBL)驱动的,它可以催化几乎所有临床上可用的β-内酰胺的水解,并且对所有临床上使用的β-内酰胺酶抑制剂具有抗性。在这项研究中,在机会病原体的多重耐药分离物中鉴定出一种未表征的MBL,吲哚金杆菌。序列分析预测该MBL(CIM-1)是具有非典型脂盒的脂蛋白。CIM-1的表征表明它是一种具有广谱活性的高亲和力碳青霉烯酶,包括所有头孢菌素和碳青霉烯类。结果还表明,CIM-1可能是具有未表征的脂质盒的膜相关MBL。使用预测工具,我们还发现了更多潜在的脂化MBLs与非规范脂质盒,突出了进一步研究脂化MBLs的必要性.