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Gene-in-gene coding generates dual-isoform Fha condensates to control type VI secretion system assembly
Journal article   Open access   Peer reviewed

Gene-in-gene coding generates dual-isoform Fha condensates to control type VI secretion system assembly

Tong-Tong Pei, Qiao-Yu Chen, Xing-Yu Wang, Amy Ma, Jia-Xin Liang, Zi-Yan Ye, Yu-Zhao Liu, Jing-Tong Su, Xiaoye Liang, Ying An, …
Nature communications, Forthcoming
26 May 2026
DOI: https://doi.org/10.1038/s41467-026-73608-w
PMID: 42191729
url
https://doi.org/10.1038/s41467-026-73608-wView
Published, Version of Record (VoR) Open

Abstract

While eukaryotes employ alternative splicing to diversify protein functions, analogous strategies in bacteria remain underexplored. Here we identify a conserved intragenic coding mechanism in Vibrio cholerae that generates two isoforms of the essential scaffold Fha and show that these isoforms cooperate through liquid-liquid phase separation to promote the assembly of the type VI secretion system (T6SS). The full-length isoform, Fha , seeds assembly by engaging the membrane complex, whereas an internally translated isoform, Fha , enhances secretion efficiency by strengthening specific interactions with baseplate components. This isoform partitioning is ecologically critical; a mutant producing only Fha is impaired in bacterial competition, susceptible to eukaryotic predation, and defective in host colonization. Both isoforms form condensates, and a single residue change within a C-terminal helix abolishes condensate formation and significantly reduces T6SS activities. The internal translation and condensate-forming residues are strictly conserved across >10,000 V. cholerae isolates and active in diverse Vibrio species. These findings define a translational-biophysical mechanism that tunes a widespread contractile protein nanomachine for ecological success.

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