Haemophilus influenzae strains possess variations in the global transcriptional profile in response to oxygen levels and this influences sensitivity to environmental stresses.

An alcohol dehydrogenase, AdhC, is required for Haemophilus influenzae Rd KW20 growth with high oxygen. AdhC protects against both exogenous and metabolically generated, endogenous reactive aldehydes. However, adhC in the strain 86-028NP is a pseudogene. Unlike the Rd KW20 adhC mutant, 86-028NP does grow with high oxygen. This suggests the differences between Rd KW20 and 86-028NP include broader pathways, such as for the maintenance of redox and metabolism that avoids the toxicity related to oxygen. We hypothesized that these differences affect their resistance to relevant toxic chemicals, including reactive aldehydes. Across a range of oxygen concentrations, despite the growth profiles of Rd KW20 and 86-028NP being similar, there was a significant variation in their sensitivity to reactive aldehydes. 86-028NP is more sensitive to methylglyoxal, formaldehyde and glycolaldehyde under high oxygen than low oxygen as well as compared to Rd KW20. Also, as oxygen levels changed the whole genome gene expression profiles of Rd KW20 and 86-028NP revealed distinctions in their transcriptomes (the iron, FNR and ArcAB regulons). These were indicative of a difference in their intracellular redox properties and we show it is this that underpins their survival against reactive aldehydes.