Böhm Maria-Elisabeth, Razavi Mohammad, Flach Carl-Fredrik, Larsson D G Joakim
Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden.
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Antibiotics (Basel). 2020 Mar 14;9(3):123. doi: 10.3390/antibiotics9030123.
AmpC-type β-lactamases severely impair treatment of many bacterial infections, due to their broad spectrum (they hydrolyze virtually all β-lactams, except fourth-generation cephalosporins and carbapenems) and the increasing incidence of plasmid-mediated versions. The original chromosomal AmpCs are often tightly regulated, and their expression is induced in response to exposure to β-lactams. Regulation of mobile expression is in many cases less controlled, giving rise to constitutively resistant strains with increased potential for development or acquisition of additional resistances. We present here the identification of two integron-encoded genes, and (integron-derived cephalosporinase), with less than 85% amino acid sequence identity to any previously annotated AmpC. While their resistance pattern identifies them as class C β-lactamases, their low isoelectric point (pI) values make differentiation from other β-lactamases by isoelectric focusing impossible. To the best of our knowledge, this is the first evidence of an gene cassette within a class 1 integron, providing a mobile context with profound potential for transfer and spread into clinics. It also allows bacteria to adapt expression levels, and thus reduce fitness costs, e.g., by cassette-reshuffling. Analyses of public metagenomes, including sewage metagenomes, show that the discovered are primarily found in Asian countries.
AmpC 型β-内酰胺酶严重影响许多细菌感染的治疗，这是由于其广谱性（它们几乎能水解所有β-内酰胺类药物，除了第四代头孢菌素和碳青霉烯类）以及质粒介导型的发病率不断上升。最初的染色体 AmpC 通常受到严格调控，其表达在接触β-内酰胺类药物时被诱导。在许多情况下，可移动表达的调控控制较少，从而产生组成型耐药菌株，其产生或获得其他耐药性的可能性增加。我们在此展示了两个整合子编码基因的鉴定，即 和 （整合子衍生的头孢菌素酶），它们与任何先前注释的 AmpC 的氨基酸序列同一性低于 85%。虽然它们的耐药模式将它们鉴定为 C 类β-内酰胺酶，但它们较低的等电点（pI）值使得通过等电聚焦与其他β-内酰胺酶区分开来变得不可能。据我们所知，这是 1 类整合子中存在 基因盒的首个证据，为其转移并传播到临床提供了具有深远潜力的可移动环境。它还使细菌能够调节表达水平，从而降低适应性成本，例如通过盒式重排。对包括污水宏基因组在内的公共宏基因组的分析表明，所发现的 主要存在于亚洲国家。
