H2S, a Bacterial Defense Mechanism against the Host Immune Response

ABSTRACT

The biological mediator hydrogen sulfide (H ₂S) 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 H ₂S provides resistance against the immune response, using two bacterial species that are common sources of nosocomial infections, Escherichia coli and Staphylococcus aureus. Elevations in H ₂S levels increased the resistance of both species to immune-mediated killing. Clearances of infections with wild-type and genetically H ₂S-deficient E. coli and S. aureus were compared in vitro and in mouse models of abdominal sepsis and burn wound infection. Also, inhibitors of H ₂S-producing enzymes were used to assess bacterial killing by leukocytes. We found that inhibition of bacterial H ₂S 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 H ₂S as a bacterial defense mechanism against the host response and implicate bacterial H ₂S inhibition as a potential therapeutic intervention in the prevention or treatment of infections.