TY - JOUR
T1 - A new class of type VI secretion system effectors can carry two toxic domains and are recognized through the WHIX motif for export
AU - Fridman, Chaya Mushka
AU - Keppel, Kinga
AU - Rudenko, Vladislav
AU - Altuna-Alvarez, Jon
AU - Albesa-Jové, David
AU - Bosis, Eran
AU - Salomon, Dor
N1 - Publisher Copyright:
© 2025 Fridman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2025/3
Y1 - 2025/3
N2 - Gram-negative bacteria employ the type VI secretion system (T6SS) to deliver toxic effectors into neighboring cells and outcompete rivals. Although many effectors have been identified, their secretion mechanism often remains unknown. Here, we describe WHIX, a domain sufficient to mediate the secretion of effectors via the T6SS. Remarkably, we find WHIX in T6SS effectors that contain a single toxic domain, as well as in effectors that contain two distinct toxic domains fused to either side of WHIX. We demonstrate that the latter, which we name double-blade effectors, require two cognate immunity proteins to antagonize their toxicity. Furthermore, we show that WHIX can be used as a chassis for T6SS-mediated secretion of multiple domains. Our findings reveal a new class of polymorphic T6SS cargo effectors with a unique secretion domain that can deploy two toxic domains in one shot, possibly reducing recipients’ ability to defend themselves.
AB - Gram-negative bacteria employ the type VI secretion system (T6SS) to deliver toxic effectors into neighboring cells and outcompete rivals. Although many effectors have been identified, their secretion mechanism often remains unknown. Here, we describe WHIX, a domain sufficient to mediate the secretion of effectors via the T6SS. Remarkably, we find WHIX in T6SS effectors that contain a single toxic domain, as well as in effectors that contain two distinct toxic domains fused to either side of WHIX. We demonstrate that the latter, which we name double-blade effectors, require two cognate immunity proteins to antagonize their toxicity. Furthermore, we show that WHIX can be used as a chassis for T6SS-mediated secretion of multiple domains. Our findings reveal a new class of polymorphic T6SS cargo effectors with a unique secretion domain that can deploy two toxic domains in one shot, possibly reducing recipients’ ability to defend themselves.
UR - https://www.scopus.com/pages/publications/105000315942
U2 - 10.1371/journal.pbio.3003053
DO - 10.1371/journal.pbio.3003053
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C2 - 40096082
AN - SCOPUS:105000315942
SN - 1544-9173
VL - 23
JO - PLoS Biology
JF - PLoS Biology
IS - 3 March
M1 - e3003053
ER -