Structural ccharacterization of the conjugative Type IV Secretion System pilus tip complex

Bacterial conjugation is the primary cause of the spread of antibiotic resistance genes, significantly contributing to the global antibiotic resistance crisis. This DNA transfer process is mediated by the Type IV Secretion System (T4SS), a large molecular machinery. A crucial component of this system is the conjugative pilus, a long extracellular filament that establishes the initial contact between donor and recipient cells, enabling DNA transfer. Despite its vital roles in host-cell recognition and penetration, the molecular details of the pilus tip remain poorly understood. Our project aims to unravel the molecular mechanisms underlying the interaction between the pilus tip and the recipient cell during bacterial conjugation. Using advanced structural approaches, including cryo- electron microscopy (cryo-EM), we aim to resolve the native structure of the pilus tip both in its resting state and during interaction with the recipient cell.