HS, a Bacterial Defense Mechanism against the Host Immune Response.

The biological mediator hydrogen sulfide (HS) is produced by bacteria and has been shown to be cytoprotective against oxidative stress and to increase the sensitivity of various bacteria to a range of antibiotic drugs. Here we evaluated whether bacterial HS provides resistance against the immune response, using two bacterial species that are common sources of nosocomial infections, and Elevations in HS levels increased the resistance of both species to immune-mediated killing. Clearances of infections with wild-type and genetically HS-deficient and were compared and in mouse models of abdominal sepsis and burn wound infection. Also, inhibitors of HS-producing enzymes were used to assess bacterial killing by leukocytes. We found that inhibition of bacterial HS production can increase the susceptibility of both bacterial species to rapid killing by immune cells and can improve bacterial clearance after severe burn, an injury that increases susceptibility to opportunistic infections. These findings support the role of HS as a bacterial defense mechanism against the host response and implicate bacterial HS inhibition as a potential therapeutic intervention in the prevention or treatment of infections.