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 different T6SSs. The H1-T6SS delivers toxins into aggressive bacteria in response to attacks mediated by 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 regulon, such as the mag operon, and GacA-independent factors, such as the outer membrane protein OprF, confer resistance to T6SS toxins. Specifically, MagD protects mainly against PG-targeting effectors, whereas OprF confers general protection against multiple effector types. We show that these mechanisms are crucial for resistance against T6SS attacks, as well as for resistance to certain antibiotics. Interestingly, some of these mechanisms also lead to higher antibiotic susceptibility, suggesting more complex links between general T6SS and antibiotic resistance.
[doi:10.25345/C5GT5FT1N]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: T6SS ; Infection ; Resistance ; DatasetType:Proteomics
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Principal Investigators: (in alphabetical order) |
Alexander Schmidt, Biozentrum, Universtiy of Basel, 4056 Basel, Switzerland, N/A |
| Submitting User: | trendsetter |
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