Type IV secretion systems: from structures to mechanisms

Bacterial conjugation is the fundamental process of unidirectional transfer of DNA from a "donor" cell to a "recipient" cell. It is the primary means by which antibiotic resistance genes spread among bacterial populations. Conjugation is mediated by a large molecular machinery termed Type IV secretion system (T4SS), embedded within the donor cell wall. In addition, some bacteria utilise T4SS to inject effector proteins into eukaryotic cells, modulating host functions to their advantage. In this review, we highlight how recent structural studies have substantially advanced our understanding of T4SS molecular mechanisms. We detail these mechanisms across four main sub-processes: assembly of the machinery, pilus biogenesis, donor-recipient cell contact, and substrate recruitment and secretion. By understanding the intricate workings of T4SS, we can gain valuable insights into bacterial evolution, virulence, and horizontal gene transfer, offering potential avenues for developing novel antibacterial strategies.