Killing of Gram-negative and Gram-positive bacteria by a bifunctional cell wall-targeting T6SS effector

Le, N.-H.; Pinedo, V.; Lopez, J.; Cava, F.; Feldman, M. F.

doi:10.1101/2021.03.04.433973

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bioRxiv · 10.1101/2021.03.04.433973

Killing of Gram-negative and Gram-positive bacteria by a bifunctional cell wall-targeting T6SS effector

Le, N.-H.·Pinedo, V.·Lopez, J.·Cava, F.·Feldman, M. F.

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Abstract

The type VI secretion system (T6SS) is a powerful tool deployed by Gram-negative bacteria to antagonize neighboring organisms. Here, we report that Acinetobacter baumannii ATCC 17978 (Ab17978) secretes D-lysine (D-Lys), increasing the extracellular pH and enhancing the peptidoglycanase activity of the T6SS effector Tse4. This synergistic effect of D-Lys on Tse4 activity enables Ab17978 to outcompete Gram-negative bacterial competitors, demonstrating that bacteria can modify their microenvironment to increase their fitness during bacterial warfare. Remarkably, this lethal combination also results in T6SS-mediated killing of Gram-positive bacteria. Further characterization revealed that Tse4 is a bifunctional enzyme consisting of both lytic transglycosylase and endopeptidase activities, thus representing a novel family of modularly organized T6SS PG degrading effectors with an unprecedented impact in antagonistic bacterial interactions. One sentence summaryBy modulating local environmental pH through D-Lys secretion, Acinetobacter baumannii enhances the activity of a bifunctional cell wall-targeting T6SS effector, increasing its killing activity against Gram-negative and -positive competitors.

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Le, N.-H., Pinedo, V., Lopez, J., Cava, F., Feldman, M. F.. 2021-03-04. Killing of Gram-negative and Gram-positive bacteria by a bifunctional cell wall-targeting T6SS effector. https://doi.org/10.1101/2021.03.04.433973

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