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The objective of this study was to determine if heterologous cyclic dipeptides could repress <jats:italic>V. cholerae<\/jats:italic> virulence factor production. To that end, three synthetic cyclic dipeptides that differed in their side chains from cFP were assayed for virulence inhibitory activity in <jats:italic>V. cholerae<\/jats:italic>. The results revealed that cyclo(valine\u2013valine) (cVV) inhibited virulence factor production by a ToxR-dependent process that resulted in the repression of the virulence regulator <jats:italic>aphA<\/jats:italic>. cVV-dependent repression of <jats:italic>aphA<\/jats:italic> was found to be independent of known <jats:italic>aphA<\/jats:italic> regulatory genes. The results demonstrated that <jats:italic>V. cholerae<\/jats:italic> was able to respond to exogenous cyclic dipeptides and implicated the hydrophobic amino acid side chains on both arms of the cyclo dipeptide scaffold as structural requirements for inhibitory activity. The results further suggest that cyclic dipeptides have potential as therapeutics for cholera treatment.<\/jats:p>","DOI":"10.1099\/mic.0.077297-0","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T04:07:06Z","timestamp":1395202026000},"page":"1054-1062","source":"Crossref","is-referenced-by-count":7,"title":["Cyclo(valine\u2013valine) inhibits Vibrio cholerae virulence gene expression"],"prefix":"10.1099","volume":"160","author":[{"given":"Amit","family":"Vikram","sequence":"first","affiliation":[{"name":"University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa M.","family":"Ante","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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