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HpaR, a MarR family transcriptional regulator, was first identified in  Escherichia coli  W for its regulation of the  hpa-meta  operon. Little else is known regarding its functionality. Here, we report that in  Yersinia pseudotuberculosis , HpaR negatively regulates the  hpa-meta  operon similar to in  E. coli  W. To investigate additional functions of HpaR, RNA sequencing was performed for both the wild-type and the Δ hpaR  mutant, which revealed that the type VI secretion system (T6SS) was positively regulated by HpaR. T6SS4 is important for bacteria resisting environmental stress, especially oxidative stress. We demonstrate that HpaR facilitates bacteria resist oxidative stress by upregulating the expression of T6SS4 in  Y .  pseudotuberculosis . HpaR is also involved in biofilm formation, antibiotic resistance, adhesion to eukaryotic cells, and virulence in mice. These results greatly expand our knowledge of the functionality of HpaR and reveal a new pathway that regulates T6SS4.

frontiers in microbiology

HpaR, the Repressor of Aromatic Compound Metabolism, Positively Regulates the Expression of T6SS4 to Resist Oxidative Stress in Yersinia pseudotuberculosis