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The antivirulence activity of PAβN was found to be dependent on the ToxR periplasmic sensing domain (PPD), suggesting that a feedback mechanism was involved in its activity. Collectively, the data indicated that PAβN inhibited V. cholerae virulence factor production by activating a ToxR-dependent metabolic feedback mechanism to repress the expression of the ToxR virulence regulon. This suggests that efflux pump inhibitors could be used as antivirulence therapeutics for the treatment of cholera and perhaps that of other Gram-negative pat