Bernut Audrey, Belon Claudine, Soscia Chantal, Bleves Sophie, Blanc-Potard Anne-Béatrice
Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier (DIMNP CNRS-UMR5235), Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
CNRS & Aix-Marseille University, Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), IMM, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
Microb Cell. 2015 Aug 13;2(9):353-355. doi: 10.15698/mic2015.09.227.
is an extracellular pathogen known to impair host phagocytic functions. However, our recent results identify MgtC as a novel actor in virulence, which plays a role in an intramacrophage phase of this pathogen. In agreement with its intracellular function, gene expression is strongly induced when the bacteria reside within macrophages. MgtC was previously known as a horizontally-acquired virulence factor important for multiplication inside macrophages in several intracellular bacterial pathogens. MgtC thus provides a singular example of a virulence determinant that subverts macrophages both in intracellular and extracellular pathogens. Moreover, we demonstrate that MgtC is required for optimal growth in Mg deprived medium, a property shared by MgtC factors from intracellular pathogens and, under Mg limitation, MgtC prevents biofilm formation. We propose that MgtC has a similar function in intracellular and extracellular pathogens, which contributes to macrophage resistance and fine-tune adaptation to the host in relation to the different bacterial lifestyles. MgtC thus appears as an attractive target for antivirulence strategies and our work provides a natural peptide as MgtC antagonist, which paves the way for the development of MgtC inhibitors.
是一种已知会损害宿主吞噬功能的细胞外病原体。然而,我们最近的研究结果表明,MgtC是毒力方面的一个新角色,它在这种病原体的巨噬细胞内阶段发挥作用。与其细胞内功能一致,当细菌存在于巨噬细胞内时,基因表达会被强烈诱导。MgtC以前被认为是一种水平获得的毒力因子,对几种细胞内细菌病原体在巨噬细胞内的增殖很重要。因此,MgtC提供了一个独特的例子,说明一种毒力决定因素在细胞内和细胞外病原体中都会破坏巨噬细胞。此外,我们证明MgtC是在缺镁培养基中实现最佳生长所必需的,这是细胞内病原体的MgtC因子共有的特性,并且在镁限制条件下,MgtC可防止生物膜形成。我们提出,MgtC在细胞内和细胞外病原体中具有相似的功能,这有助于巨噬细胞抵抗,并根据不同的细菌生活方式对宿主进行微调适应。因此,MgtC似乎是抗毒力策略的一个有吸引力的靶点,我们的工作提供了一种天然肽作为MgtC拮抗剂,为开发MgtC抑制剂铺平了道路。