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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Gram-negative bacteria can deliver toxic proteins directly into neighboring cells with the Type VI secretion system (T6SS). The T6SS is a competition mechanism for inter-bacterial and host-microbe interactions used by bacteria including pathogens like Vibrio cholerae, which resides in aquatic environments and in the gut of cholera patients. The current pathoadaptive model based on patient-derived V. cholerae predicts the transcriptional control of the major T6SS locus requires either QstR or TfoY transcription regulators. In clinical strain C6706, quorum sensing and chitin upregulate QstR, and low c-di-GMP permit TfoY in V52. However, the mechanisms of QstR and TfoY activation are still unclear. Previously demonstrated environmental strains (ES1-24) exhibit constitutive T6SS without chitin induction, we sought to explore the sufficiency of current models. We found ΔqstR and ΔtfoY from 4 of the ESs, including ES2, had little or no effect on T6SS killing. To investigate how C6706, V52, and ES2 differ in T6SS activation, we aligned intergenic regions (IGRs) 5’ to the major T6SS locus and identified SNPs that distinguish the IGRs. We revealed a critical SNP responsible for T6SS control. A guanine (G) at this position was required for QstR dependence while a thymine (T) eliminated QstR dependence and permits constitutive T6SS activity. Genomic analysis reveals conservation at this position - a G in patient isolates and a T in environmental isolates. I hypothesize the specific SNP identified may allow V. cholerae to easily interconvert its T6SS regulation between a mode that is beneficial for interbacterial competition in natural habitats to one more tightly controlled with a human host setting. These findings also provide insights into how simple mutations in non-coding regions can rewire expression of genes under control of existing regulatory factors.
