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Hemolysin-coregulated protein 1 (Hcp1) is a hallmark structural component of the Type VI Secretion System (T6SS), a contractile nanomachine used by many Gram-negative bacteria to inject effector proteins into target cells (Mougous et al., Science, 2006). Hcp1 monomers assemble into hexameric rings that stack to form a rigid inner tube, which is propelled out of the cell by a contractile sheath to penetrate the membranes of prey bacteria or host eukaryotic cells (Pukatzki et al., PNAS, 2006). This system is essential for bacterial pathogenesis, inter-bacterial competition, and environmental survival in species such as Pseudomonas aeruginosa, Vibrio cholerae, and Burkholderia pseudomallei (Cascales and Cambillau, Phil. Trans. R. Soc. B, 2012). As a secreted protein and a key driver of virulence, Hcp1 is a significant target for the development of anti-infective strategies, including small-molecule inhibitors of T6SS assembly and vaccine candidates (UniProt KB: P0C6Q4). Furthermore, the detection of Hcp1 in patient samples like serum or sputum serves as a specific biomarker for active T6SS-mediated infection (Sana et al., J. Infect. Dis., 2016).
Inhibition of Type VI secretion system (T6SS) assembly by preventing Hcp1 polymerization or blocking the secretion tube conduit.
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