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A Type VII-secreted toxin enables inter-mycobacterial competition

Lookup NU author(s): Dr Sam BenedictORCiD, Dr Kieran BowranORCiD, Eunice Lee, Jean-Lou ReyreORCiD, Dr Nicole Mietrach, Dr Elizabeth ChanORCiD, Dr Emmanuele SeveriORCiD, Ellie Boardman, Manuel BanzhafORCiD, Dr Elisabeth LoweORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© The Author(s) 2026.Most bacteria have evolved mechanisms to compete with other bacteria, often through the specialised secretion of proteinaceous toxins. However, mycobacteria have not previously been reported to engage in this form of competition. The thick and unusual mycobacterial cell wall, comprised of peptidoglycan, arabinogalactan and mycolic acids, is generally thought to be highly protective to these bacteria. Here, we show that some mycobacteria can use endo-D-arabinanases of the GH183 family for inter-bacterial competition. These microorganisms secrete an endo-D-arabinanase effector via the type VII secretion system (T7SS) that cleaves the arabinogalactan layer of the mycobacterial cell envelope. We describe the molecular basis for this activity using structural biology and biochemistry, and identify a protein family that protects the bacterium from the activity of this toxin. The widespread presence of genes potentially encoding similar T7SS-secreted toxins in the Mycobacteriales suggests extensive inter-mycobacterial competition.


Publication metadata

Author(s): Benedict ST, Bowran K, Lee EKE, Reyre J-L, Ahmad H, Franklin A, Mietrach NA, Han C-R, Chan JM, Layton AJ, Severi E, Boardman ER, Anochshenko K, Goudge G, Caulton SG, Lowary TL, Lovering AL, Banzhaf M, Lowe EC, Palmer T, Moynihan PJ

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2026

Volume: 17

Issue: 1

Print publication date: 06/08/2026

Online publication date: 23/06/2026

Acceptance date: 03/06/2026

Date deposited: 18/08/2026

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-026-74429-7

DOI: 10.1038/s41467-026-74429-7

Data Access Statement: Thecrystallographic data generated in this study have been deposited in the PDB under accession codes 9MXM, 9MYT, and 9MZ5. DNA sequencing results are deposited in the European Nucleotide Archive under project PRJEB85598. All AlphaFold 3 models are available in Supplementary Data 1. The remaining data generated in this study are provided in the Supplementary Information and Source Data file. Source data are provided with this paper. The R script used for fluorescence data analysis is available as Sup plementary Software 1 and at GitHub (https://github.com/ Hudaahmadd/Fluorescence-Analysis)

PubMed id: 42336839


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Funding

Funder referenceFunder name
BB/S010122/1
BB/X006298/1
BB/X00841X/1
BB/X016749/1
BBSRC
Darwin Trust of Edinburgh
European Research Council under the Synergy Grant CombaT7 (project ID: 101167433).
Springboard award (SBF005/1112)
Wellcome Trust 226644/Z/22/Z
UKRI Future Leaders Fellowship (MR/V027204/1)
Wellcome Trust 224151/Z/21/Z

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