A glutathione-based system for defense against carbonyl stress in Haemophilus influenzae

Abstract

BACKGROUND adhC from Haemophilus influenzae encodes a glutathione-dependent alcohol dehydrogenase that has previously been shown to be required for protection against killing by S-nitrosoglutathione (GSNO). This group of enzymes is known in other systems to be able to utilize substrates that form adducts with glutathione, such as aldehydes. RESULTS Here, we show that expression of adhC is maximally induced under conditions of high oxygen tension as well as specifically with glucose as a carbon source. adhC could also be induced in response to formaldehyde but not GSNO. An adhC mutant was more susceptible than wild-type Haemophilus influenzae Rd KW20 to killing by various short chain aliphatic aldehydes, all of which can be generated endogenously during cell metabolism but are also produced by the host as part of the innate immune response. CONCLUSIONS These results indicate that AdhC plays a role in defense against endogenously generated reactive carbonyl electrophiles in Haemophilus influenzae and may also play a role in defense against the host innate immune system.