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

The Type VI Secretion Systems (T6SSs) is a molecular nanomachine that injects toxic effector proteins into the environment or neighbouring cells, and thus plays an important role in interbacterial competition and host antagonism during infection. Pseudomonas aeruginosa is an opportunistic bacterial pathogen that encodes three different T6SS. The H1-T6SS delivers toxins into aggressive bacteria in response to attacks mediated by the their own T6SS. This suggests that P. aeruginosa has the ability to survive T6SS assaults. However, the resistance mechanisms are poorly characterized. In this work, 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 TCS regulon, such as the mag operon, and GacA-independent factors, such as the outer membrane protein OprF, confer resistance to T6SS toxins. We show that outer membrane anchoring to the peptidoglycan is crucial for resistance against T6SS attacks, as well as for resistance to different antibiotics, suggesting a link between general T6SS resistance and antibiotic resistance.