is a neutrophilic enteric pathogen that is extremely sensitive to acid. As passages through the host gastrointestinal tract it is exposed to a variety of environmental stresses including low pH and volatile fatty acids. Exposure to acidic environments induces expression of the acid tolerance response. A key component of the acid tolerance response is the system, which is encoded by and the operon. CadB is a lysine/cadaverine antiporter and CadA is a lysine decarboxylase and these function together to counter low intracellular and extracellular pH. CadC is a membrane-associated transcription factor that activates expression in response to acidic conditions. Herein we investigated the role of the LysR-type transcriptional regulator LeuO in the acid tolerance response. Transcriptional reporter assays revealed that expression repressed transcription, indicating that LeuO was a repressor. Consistent with this, expression was inversely linked to lysine decarboxylase production and overexpression resulted in increased sensitivity to organic acids. Overexpression of in a mutant potentiated killing by organic acids, suggesting that the function of in the acid tolerance response extended beyond its regulation of the system. Collectively, these studies have identified a new physiological role for LeuO in acid tolerance.


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