The Breadth and Molecular Basis of Hcp-Driven Type VI Secretion System Effector Delivery
Sophie A. Howard, R. Christopher D. Furniss, Dora Bonini, Himani Amin, Patricia Paracuellos, David Zlotkin, Tiago R. D. Costa, Asaf Levy, Despoina A. I. Mavridou, Alain Filloux
Abstract
The type VI secretion system (T6SS) is an effective weapon used by bacteria to outgrow or kill competitors. It can be used by endogenous commensal microbiota to prevent invasion by pathogens or by pathogens to overcome resident flora and successfully colonize a host or a specific environmental niche. The T6SS is a key contributor to this continuous arms race between organisms as it delivers a multitude of toxins directed at essential processes, such as nucleic acid synthesis and replication, cell wall and membrane integrity, protein synthesis, or cofactor abundance. Many T6SS toxins with unknown function remain to be discovered, whose yet-uncharacterized targets could be exploited for antimicrobial drug design. The systematic search for these toxins is not facilitated by the presence of readily recognizable T6SS motifs, and unbiased screening approaches are thus required. Here, we successfully used a known shuttle for cargo T6SS effectors, Hcp, as bait to identify uncharacterized toxins.