Univ. Limoges, INSERM, CHU Limoges, RESINFIT, U1092, F-87000 Limoges, France.
Aix Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France.
Int J Antimicrob Agents. 2019 Apr;53(4):491-499. doi: 10.1016/j.ijantimicag.2018.11.012. Epub 2018 Nov 23.
Integrons recruit resistance genes through integrase-driven recombination events that are regulated by the bacterial SOS response and require the repressor LexA. Class 1 integrons genes are expressed from a common promoter, Pc, of which at least 5 predominant variants, classified from weak to strong, have been described. In Escherichia coli, there is an intertwined regulation between gene cassette expression and integrase activity: the stronger the promoter, the weaker the integrase. Class 1 integrons have been frequently described in Acinetobacter baumannii. However, Acinetobacter spp. lack the LexA repressor, suggesting that the integrase is constitutively expressed. We characterized the integron content of 83 clinical and environmental A. baumannii strains. We found a predominance of Pc variants described as strong in E. coli. The Pc expression level was 2- to 4-fold lower in A. baumannii than in E. coli, and the diversity of the gene cassette array was low. In A. baumannii, integrons with a PcS promoter might have been selected to enable sufficient resistance while avoiding the toxicity of a highly active integrase. Furthermore, a transcriptional interference between PcS and PintI1 (as shown in E. coli) may limit the expression of the integrase and thus counterbalance the lack of LexA-driven integrase repression to prevent the cost of the integrase.
整合子通过整合酶驱动的重组事件招募抗性基因,这些事件受到细菌 SOS 反应的调节,需要抑制因子 LexA。类 1 整合子基因由一个共同的启动子 Pc 表达,其中至少描述了 5 种主要的变体,从弱到强进行分类。在大肠杆菌中,基因盒表达和整合酶活性之间存在交织的调节:启动子越强,整合酶越弱。类 1 整合子在鲍曼不动杆菌中经常被描述。然而,不动杆菌属缺乏 LexA 抑制因子,这表明整合酶是组成型表达的。我们对 83 株临床和环境分离的鲍曼不动杆菌菌株的整合子进行了特征描述。我们发现,大肠杆菌中描述为强的 Pc 变体占主导地位。Pc 在鲍曼不动杆菌中的表达水平比在大肠杆菌中低 2-4 倍,而且基因盒阵列的多样性较低。在鲍曼不动杆菌中,具有 PcS 启动子的整合子可能被选择以提供足够的抗性,同时避免高活性整合酶的毒性。此外,PcS 和 PintI1 之间的转录干扰(如在大肠杆菌中所示)可能会限制整合酶的表达,从而平衡缺乏 LexA 驱动的整合酶抑制作用,以防止整合酶的成本。