Antimicrobial resistance represents a major global health concern and environmental bacteria are considered a source of resistance genes. Carbapenems are often used as the last antibiotic option to treat multidrug-resistant bacteria. Metallo-β-lactamases (MBLs) are able to render resistance to almost all β-lactam antibiotics, including carbapenems. Unfortunately, there are no inhibitors against MBLs for clinical use. Subclass B2 MBLs are the only enzymes working as strict carbapenemases, under-represented, encoded in chromosome genes and only functional as mono-zinc enzymes. Despite current efforts in MBLs inhibitor development, B2 carbapenemase activity is especially difficult to suppress, even in vitro. In this study we characterized BioF, a novel subclass B2 MBL identified in a new environmental Pseudomonas sp. strain isolated from an on-farm biopurification system (BPS). Although bla_BioF is most likely a chromosomal gene, it is found in a genomic island and may represent a step previous to the horizontal transmission of B2 genes. The new B2 MBL is active as a mono-zinc enzyme and is a potent carbapenemase with incipient activity against some cephalosporins. BioF activity is not affected by excess zinc and is only inhibited at high metal chelator concentrations. The discovery and characterization of B2 MBL BioF as a potent carbapenemase in a BPS bacterial isolate emphasizes the importance of exploring antibiotic resistances existing in the environmental microbiota under the influence of human activities before they could emerge clinically.

中文翻译：

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BioF 是一种来自假单胞菌属的新型 B2 金属-β-内酰胺酶。从农场生物净化系统中分离出来

抗菌素耐药性代表了一个主要的全球健康问题，环境细菌被认为是耐药基因的来源。碳青霉烯类通常被用作治疗多重耐药细菌的最后抗生素选择。金属-β-内酰胺酶 (MBL) 能够对几乎所有 β-内酰胺类抗生素产生耐药性，包括碳青霉烯类。不幸的是，临床上没有针对 MBL 的抑制剂。B2 亚类 MBL 是唯一作为严格碳青霉烯酶发挥作用的酶，其代表性不足，编码在染色体基因中，仅作为单锌酶发挥作用。尽管目前正在努力开发 MBLs 抑制剂，但 B2 碳青霉烯酶活性特别难以抑制，即使在体外也是如此。在这项研究中，我们对 BioF 进行了表征，这是一种在新环境中发现的新型 B2 MBL 亚类。假单胞菌属 从农场生物纯化系统 (BPS) 中分离出的菌株。尽管bla _BioF很可能是染色体基因，但它存在于基因组岛中，可能代表 B2 基因水平传递之前的一步。新的 B2 MBL 作为单锌酶具有活性，是一种强效碳青霉烯酶，对某些头孢菌素具有初始活性。BioF 活性不受过量锌的影响，仅在高金属螯合剂浓度下受到抑制。B2 MBL BioF 作为 BPS 细菌分离物中的强效碳青霉烯酶的发现和表征强调了在人类活动影响下探索环境微生物群中存在的抗生素耐药性的重要性，然后才能出现在临床上。