Abstract
Vibrio cholerae, the facultative pathogen responsible for cholera disease, continues to pose a global health burden. Its persistence can be attributed to a flexible genetic tool kit that allows for adaptation to different environments with distinct carbon sources, including the six-carbon sugar alcohol mannitol. V. cholerae takes up mannitol through the transporter protein MtlA, whose production is downregulated at the posttranscriptional level by MtlS, a cis antisense small RNA (sRNA) whose promoter lies within the mtlA open reading frame. Though it is known that mtlS expression is robust under growth conditions lacking mannitol, it has remained elusive as to what factors govern the steady-state levels of MtlS. Here, we show that manipulating mtlA transcription is sufficient to drive inverse changes in MtlS levels, likely through transcriptional interference. This work has uncovered a cis-acting sRNA whose expression pattern is predominantly controlled by transcription of the sRNA's target gene.IMPORTANCEVibrio cholerae is a bacterial pathogen that relies on genetic tools, such as regulatory RNAs, to adapt to changing extracellular conditions. While many studies have focused on how these regulatory RNAs function, fewer have focused on how they are themselves modulated. V. cholerae expresses the noncoding RNA MtlS, which can regulate mannitol transport and use, and here we demonstrate that MtlS levels are controlled by the level of transcription occurring in the antisense direction. Our findings provide a model of regulation describing how bacteria like V. cholerae can modulate the levels of an important regulatory RNA. Our work contributes to knowledge of how bacteria deploy regulatory RNAs as an adaptive mechanism to buffer against environmental flux.
Highlights
Vibrio cholerae, the facultative pathogen responsible for cholera disease, continues to pose a global health burden
Given that MtlS small RNA (sRNA) levels in V. cholerae are high under all tested growth conditions lacking mannitol but barely detectable when cells are grown in minimal medium supplemented with only mannitol, we speculated whether mannitol played a role in repressing MtlS levels
We provide evidence for a regulatory model detailing the expression pattern of MtlS, a cis antisense RNA from V. cholerae whose function as a repressor of mtlA has been well defined but whose origin of regulation has yet to be dissected
Summary
The facultative pathogen responsible for cholera disease, continues to pose a global health burden. A facultative pathogen, V. cholerae must adapt to environmental fluctuations both within and between its two primary habitats: the aquatic environment and the human small intestine [3] To buffer against such variation, which can include changes in nutrient availability, salinity, temperature, and acidity, V. cholerae exercises diverse regulatory mechanisms to alter its gene expression profile [4,5,6,7,8]. One such method of genetic regulation entails the production of regulatory small RNAs (sRNAs), short, usually noncoding RNAs that can activate and/or repress the expression of their target genes at the transcriptional and/or posttranscriptional level through an array of distinct mechanisms [9,10,11]. The importance and function of these antisense transcripts, including the cis-acting sRNAs, warrant attention
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