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

Nguyen Hung Le, Victor Pinedo, Juvenal Lopez, Felipe Cava, Mario F. Feldman

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 out-compete 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 family of modularly organized T6SS peptidoglycan-degrading effectors with an unprecedented impact in antagonistic bacterial interactions.

Original languageEnglish
Article numbere2106555118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number40
DOIs
StatePublished - Oct 5 2021

Keywords

  • Effector
  • Microenvironment
  • Peptidoglycan
  • T6SS

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