Maffo-Woulefack Robine, Ali Abbas Mohamad, Laroussi Haifa, Cappèle Julien, Romero-Saavedra Felipe, Ramia Nancy, Robert Emilie, Mathiot Sandrine, Soler Nicolas, Roussel Yvonne, Fronzes Rémi, Huebner Johannes, Didierjean Claude, Favier Frédérique, Leblond-Bourget Nathalie, Douzi Badreddine
Université de Lorraine, INRAE, DynAMic, F-54000 Nancy, France.
Université de Lorraine, CNRS, CRM2, F-54000 Nancy, France.
Sci Adv. 2025 Jan 24;11(4):eadq5975. doi: 10.1126/sciadv.adq5975. Epub 2025 Jan 22.
Bacterial type IV secretion systems (T4SSs) are widespread nanomachines specialized in the transport across the cell envelope of various types of molecules including mobile genetic elements during conjugation. Despite their prevalence in Gram-positive bacteria, including relevant pathogens, their assembly and functioning remain unknown. This study addresses these gaps by investigating VirB8 proteins, known to be central components of conjugative T4SSs in Gram-positive bacteria. However, the functional packing and precise role of VirB8 in T4SSs biology remain undefined. Our findings elucidate the nature of VirB8 proteins as cell wall components, where they multimerize and exhibit a conserved assembly pattern, distinct from VirB8 in Gram-negative bacteria. We also demonstrate that VirB8 proteins interact with other T4SS subunits and DNA, indicating their pivotal role in the building of the DNA translocation channel across the cell wall. We lastly propose a distinct architecture for conjugative T4SSs in Gram-positive bacteria compared to their Gram-negative counterparts, possibly attributed to the differences in the cell wall structure.
细菌IV型分泌系统（T4SSs）是广泛存在的纳米机器，专门用于在接合过程中跨细胞膜转运包括移动遗传元件在内的各种类型的分子。尽管它们在革兰氏阳性菌（包括相关病原体）中普遍存在，但其组装和功能仍不清楚。本研究通过研究VirB8蛋白来填补这些空白，已知VirB8蛋白是革兰氏阳性菌中接合性T4SSs的核心成分。然而，VirB8在T4SSs生物学中的功能组装和精确作用仍不明确。我们的研究结果阐明了VirB8蛋白作为细胞壁成分的性质，它们在细胞壁中多聚化并呈现出保守的组装模式，这与革兰氏阴性菌中的VirB8不同。我们还证明了VirB8蛋白与其他T4SS亚基和DNA相互作用，表明它们在构建跨细胞壁的DNA转运通道中起关键作用。最后，我们提出了革兰氏阳性菌中接合性T4SSs与革兰氏阴性菌不同的独特结构，这可能归因于细胞壁结构的差异。
