Mechanisms of P. aeruginosa resistance to Type VI Secretion System attacks

Abstract

The Type VI Secretion System (T6SS) is a molecular nanomachine that injects toxic effector proteins into the environment or neighbouring cells, playing an important role in interbacterial competition and host antagonism during infection. Pseudomonas aeruginosa encodes three T6SSs. The H1-T6SS delivers toxins in response to attacks mediated by the T6SS of aggressive bacteria, suggesting that P. aeruginosa can resist T6SS assaults. The mechanisms of resistance are poorly characterized. Here, we performed a CRISPRi screen to identify pathways involved in resistance to T6SS effectors of Acinetobacter baylyi and Vibrio cholerae. We show that members of the GacA/GacS regulon, such as the mag operon or aas, and GacA-independent factors, such as the outer membrane protein OprF, confer resistance to different types of T6SS toxins. Interestingly, some of these T6SS resistance mechanisms lead to higher antibiotic susceptibility, suggesting complex evolutionary links between T6SS and antibiotic resistance.