The type VI secretion system of Acinetobacter: mechanisms, biology and therapeutic potential

The Type VI secretion system (T6SS) is widely recognized as a contractile nanomachine that mediates interbacterial antagonism, yet its biological roles and evolutionary logic vary substantially across bacterial lineages. In this Review, we synthesize recent advances in the Acinetobacter T6SS field and propose a unifying perspective in which the system functions as a context-dependent fitness module rather than a constitutive virulence weapon. We highlight how Acinetobacter has rewired a single T6SS platform through non-canonical structural solutions, multilayered regulatory integration, and an unusually expansive effector repertoire. Beyond microbial competition, emerging clinical and experimental evidence links T6SS activity to host immune amplification, disease severity, and the dynamics of horizontal gene transfer and antibiotic resistance. By integrating structural biology, regulatory logic, effector function, and clinical observations, this Review reframes the Acinetobacter T6SS as an adaptable system that balances aggression, persistence, and metabolic cost in polymicrobial and host-associated environments. This perspective not only advances conceptual understanding of T6SS diversity but also highlights translational opportunities for diagnostics, vaccines, and anti-virulence strategies targeting multidrug-resistant Acinetobacter infections.