Abstract
Vibrio cholerae, the etiological pathogen of cholera, employs its type VI secretion system (T6SS) as an effective weapon to survive in highly competitive communities. Antibacterial and anti-eukaryotic functions of the T6SS depend on its secreted effectors that target multiple cellular processes. However, the mechanisms that account for effector diversity and different effectiveness during interspecies competition remain elusive. Here we report that environmental cations and temperature play a key role in dictating cellular response and effector effectiveness during interspecies competition mediated by the T6SS of V. cholerae. We found that V. cholerae could employ its cell-wall-targeting effector TseH to outcompete the otherwise resistant Escherichia coli and the V. cholerae immunity deletion mutant ∆tsiH when Mg2+ or Ca2+ was supplemented. Transcriptome and genetic analyses demonstrate that the metal-sensing PhoPQ two-component system is important for Mg2+-dependent sensitivity. Competition analysis in infant mice shows that TseH was active under in vivo conditions. Using a panel of V. cholerae single-effector active mutants, we further show that E. coli also exhibited variable susceptibilities to other T6SS effectors depending on cations and temperatures, respectively. Lastly, V. cholerae effector VasX could sensitize Pseudomonas aeruginosa to its intrinsically resistant antibiotic irgasan in a temperature-dependent manner. Collectively, these findings suggest that abiotic factors, that V. cholerae frequently encounters in natural and host environments, could modulate cellular responses and dictate the competitive fitness conferred by the T6SS effectors in complex multispecies communities.
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Acknowledgements
This work was supported by funding from National Key R&D Program of China (2020YFA0907200), National Natural Science Foundation of China (31770082 and 32030001), Shenzhen Science and Technology Program (JCYJ20210324115611032 and KQTD20200909113758004), Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Canada Research Chair program. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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TD conceived the project. MT performed most of the experiment and data analysis. TP, ZW, and HL performed experiments. QX and YF performed animal infection. XW contributed to RNA-seq data analysis. MT prepared the first draft. TD contributed to the revision with assistance from MT and TP.
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Tang, MX., Pei, TT., Xiang, Q. et al. Abiotic factors modulate interspecies competition mediated by the type VI secretion system effectors in Vibrio cholerae. ISME J 16, 1765–1775 (2022). https://doi.org/10.1038/s41396-022-01228-5
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DOI: https://doi.org/10.1038/s41396-022-01228-5
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