HcpR mediates protection against nitrosative stress in Clostridioides difficile

Nitrosative stress is one of the key stressors that pathogenic bacteria, including Clostridioides difficile, encounter in the host. HcpR is a transcriptional regulator that has been shown to mediate protection against nitrosative stress in bacteria. However, its role in nitrosative stress defense among clinically important anaerobic pathogens like C. difficile is largely unexplored. In this study, we demonstrated that hcpR plays a key role in enabling C. difficile to survive against various reactive nitrogen species responsible for nitrosative stress. Through transcriptomic analysis, we show that hcpR controls other regulon in response to nitrosative stress. The study also reveals that, in addition to defense against nitrosative stress, hcpR also influences C. difficile toxin production, one of the main virulence factors of the pathogen.