In humans, the
free radical nitric oxide (NO) is a concentration-dependent multifunctional signaling or toxic molecule that modulates various physiological and
pathological processes, and innate immunity against
bacterial infections. Because the expression of bacterial genes encoding
nitrite reductase (AniA) and NO
reductase (NorB) is highly upregulated in biofilms in vitro, it is important to investigate whether bacterial NO-metabolism might subvert host NO signaling and play pathogenic roles during
infection. The Moraxella catarrhalis AniA and NorB directly function in production and reduction of NO. Using M. catarrhalis-human bronchial epithelial cell (HBEC) co-cultures, we recently reported AniA/
nitrite-dependent cytotoxic effects on HBECs, including altered
protein profiles of HBECs and induced HBEC apoptosis, suggesting bacterial
nitrite reduction likely dysregulates host cell gene expression. To further clarify whether
nitrite reduction-derived NO or
nitrite-dependent stimulation of bacterial growth was responsible for adverse effects on HBECs, we monitored bacterial
nitrite reduction, levels of NO in co-cultures and resulted dynamic effects on HBEC proliferation and bacterial viability. This study demonstrated that M. catarrhalis
nitrite reduction-derived NO was responsible for observed adverse effects on HBECs at mid-to-late stages of
infection. More importantly, our data showed that while
nitrite promoted bacterial growth and biofilm formation at early hours of
infection,
nitrite reduction-derived NO was toxic towards M. catarrhalis in maturing biofilms, suggesting
nitrite reduction-derived NO might be a possible dualistic mechanism by which M. catarrhalis promotes diseases and spontaneous resolutions.