The P. aeruginosa effector Tse5 forms membrane pores disrupting the membrane potential of intoxicated bacteria

The Pseudomonas aeruginosa Type 6 secretion effector Tse5 forms pores in the cytoplasmic membrane when ectopically produced and hence has a bacteriolytic effect by depolarising the inner membrane potential. The type VI secretion system (T6SS) of Pseudomonas aeruginosa injects effector proteins into neighbouring competitors and host cells, providing a fitness advantage that allows this opportunistic nosocomial pathogen to persist and prevail during the onset of infections. However, despite the high clinical relevance of P. aeruginosa, the identity and mode of action of most P. aeruginosa T6SS-dependent effectors remain to be discovered. Here, we report the molecular mechanism of Tse5-CT, the toxic auto-proteolytic product of the P. aeruginosa T6SS exported effector Tse5. Our results demonstrate that Tse5-CT is a pore-forming toxin that can transport ions across the membrane, causing membrane depolarisation and bacterial death. The membrane potential regulates a wide range of essential cellular functions; therefore, membrane depolarisation is an efficient strategy to compete with other microorganisms in polymicrobial environments.

Automated summary

This study reveals the molecular mechanism of Tse5-CT, the toxic product of the Pseudomonas aeruginosa T6SS. Tse5-CT is a pore-forming toxin that depolarizes the bacterial membrane, leading to bacterial death. This finding highlights the importance of membrane depolarization as a competitive strategy in polymicrobial environments.