Haemophilus influenzae is a gram-negative bacterium that causes infections such as otitis media, pneumonia, and meningitis and can especially affect at-risk populations, such as those with chronic lung disease and immunocompromised patients (1). During the past several years, vaccines for specific H. influenzae strains have reduced case numbers, but antibiotic resistant infections caused by other strains, especially nontypeable H. influenzae (NTHi), are becoming a concern (1, 2).
H. influenzae is adept at avoiding detection by the immune system by using sialic acids, a carbohydrate commonly found on most mammalian cell surfaces, on its own cell surface as a disguise (3). Unlike other H. influenzae strains that have a polysaccharide capsule, NTHi uses sialic acids attached to glycolipids on its outer membrane to disguise itself (3). NTHi's use of sialic acids during infections has been thoroughly researched. However, the regulatory mechanism of the sialic acid metabolism is yet to be determined in H. influenzae. Previous research demonstrates that the transcriptional regulators HiNanR and cAMP receptor protein (CRP) are involved in regulating the operons (3, 4). It is proposed that these two proteins can function together as a complex, altering transcription rates in response to the presence of sialic acids and changing glucose concentrations in the bacterium (3, 4).
My PhD project is based on investigating the regulation mechanism by which HiNanR and CRP interact with and regulate the genes, with a focus on structural biology and functional studies. The results could provide more insight into the mechanics of gene regulation during NTHi infections, and possibly uncover new drug targets for future antibiotics.