INRAE, Université de Tours, ISP, Nouzilly, France.
INSERM, Université de Limoges, CHU de Limoges, RESINFIT, Limoges, France.
Microbiol Spectr. 2023 Feb 14;11(1):e0220122. doi: 10.1128/spectrum.02201-22. Epub 2022 Dec 6.
The broad-host-range IncC plasmid family and the integrative mobilizable genomic island 1 (SGI1) and its derivatives enable the spread of medically important antibiotic resistance genes among Gram-negative pathogens. Although several aspects of the complex functional interactions between IncC plasmids and SGI1 have been recently deciphered regarding their conjugative transfer and incompatibility, the biological signal resulting in the hijacking of the conjugative plasmid by the integrative mobilizable element remains unknown. Here, we demonstrate that the conjugative entry of IncC/IncA plasmids is detected at an early stage by SGI1 through the transient activation of the SOS response, which induces the expression of the SGI1 master activators SgaDC, shown to play a crucial role in the complex biology between SGI1 and IncC plasmids. Besides, we developed an original tripartite conjugation approach to directly monitor SGI1 mobilization in a time-dependent manner following conjugative entry of IncC plasmids. Finally, we propose an updated biological model of the conjugative mobilization of the chromosomal resistance element SGI1 by IncC plasmids. Antimicrobial resistance has become a major public health issue, particularly with the increase of multidrug resistance (MDR) in both animal and human pathogenic bacteria and with the emergence of resistance to medically important antibiotics. The spread between bacteria of successful mobile genetic elements, such as conjugative plasmids and integrative elements conferring multidrug resistance, is the main driving force in the dissemination of acquired antibiotic resistances among Gram-negative bacteria. Broad-host-range IncC plasmids and their integrative mobilizable SGI1 counterparts contribute to the spread of critically important resistance genes (e.g., extended-spectrum β-lactamases [ESBLs] and carbapenemases). A better knowledge of the complex biology of these broad-host-range mobile elements will help us to understand the dissemination of antimicrobial resistance genes that occurred across borders.
广泛宿主范围的 IncC 质粒家族和整合可移动基因组岛 1（SGI1）及其衍生物使重要的医学抗生素抗性基因在革兰氏阴性病原体中传播。尽管最近已经解析了 IncC 质粒和 SGI1 之间复杂的功能相互作用的几个方面，包括它们的共轭转移和不兼容性，但导致整合可移动元件劫持共轭质粒的生物学信号仍然未知。在这里，我们证明 IncC/IncA 质粒的共轭进入被 SGI1 通过 SOS 反应的短暂激活早期检测到，这诱导了 SGI1 主激活子 SgaDC 的表达，表明其在 SGI1 和 IncC 质粒之间的复杂生物学中发挥关键作用。此外，我们开发了一种原始的三方共轭方法，以直接监测 IncC 质粒共轭进入后 SGI1 的时间依赖性动员。最后，我们提出了一个更新的生物模型，用于 IncC 质粒通过染色体抗性元件 SGI1 的共轭动员。 抗生素耐药性已成为一个主要的公共卫生问题，特别是在动物和人类病原菌中多药耐药（MDR）的增加以及对重要医学抗生素的耐药性的出现。成功的可移动遗传元件（如共轭质粒和赋予多药耐药性的整合元件）在细菌之间的传播是革兰氏阴性菌中获得性抗生素耐药性传播的主要驱动力。广泛宿主范围的 IncC 质粒及其整合可移动的 SGI1 对应物有助于传播重要的抗性基因（例如，扩展谱β-内酰胺酶[ESBLs]和碳青霉烯酶）。更好地了解这些广泛宿主范围的移动元件的复杂生物学将有助于我们理解跨越边界的抗菌药物耐药基因的传播。
