Adaptation to anaerobiosis in H influenzae pathogenesis

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DESCRIPTION (provided by applicant): Haemophilus influenzae is a common asymptomatic colonizer of the upper respiratory tract, yet also causes a range of invasive diseases such as otitis media, a middle ear infection that produces acute pain, distress and temporary or permanent hearing loss in children. The presence of obligate anaerobic species with H. influenzae in the middle ear fluid and the nasopharynx of otitis media patients indicates that H. influenzae encounters low oxygen conditions in vivo. H. influenzae possesses redox-responsive systems found in several other bacterial pathogens. The participation of these redox-responsive systems in altering global gene expression in response to oxygen deprivation will be investigated by characterizing the expression profiles of the nitrate and nitrite reductases. Preliminary data indicate that nitrate and nitrite reductase expression in H. influenzae is mediated by environmental signals, such as substrate availability and environmental oxygen levels. Additionally, the in vitro characterization of the nitrate and nitrite reductase expression profiles permits the development of the reductase-encoding genes as reporters for the physiological state of H. influenzae during infant rat infection. Therefore, the importance of this study is to not only yield insight into the regulatory processes of redox sensing in H. influenzae, but also to characterize the physiological state of this bacterium within host niches.