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Background and Interests:
Haemophilus influenzae (Hi) is an opportunistic pathogen present in the nasopharynx of approximately 75 percent of healthy children and adults. Hi causes otitis media (OM), arthritis, otorrhea, sinusitis, epiglottitis, bronchitis, conjunctivitis, meningitis, and pneumonia. Furthermore, Hi is the first pathogen associated with chronic obstructive pulmonary disease and cystic fibrosis pneumonia. The socio and economic impacts of OM are enormous, and Hi is responsible for approximately one-third of all OM infections. OM is the most common reason for an ill child to visit a physician; it is also the primary diagnosis for which antibiotics are prescribed; and the most common reason that children undergo surgery with general anesthesia . The economic burden of OM is estimated at approximately 5 billion dollars a year. Today's routine immunization against the b-capsule form of Hi is very effective, but ineffective against the increasingly prevalent non-capsulated form. As a result, there is a tremendous need for the identification of targets for drug and vaccine development.
Our lab has identified and annotated a large polymorphic protein family in Hi with conserved Sel1-like repeats (SLR), which are modular repeats ideal for protein-protein interactions. Proteins from this family are predicted to be surface exposed and contain variable numbers of repeats per sequence, as well as different numbers of gene copies per strain suggesting it is an antigenetically variant protein under immune pressure. We have named this protein family variable Hi SLR (vHiSLR). In all vHiSLR genes, the N-terminal region consists of a signal peptide followed by two or more sel-1 like repeats and a C-terminal tail characterized by two equidistant cysteine residues. Furthermore, close orthologues in Legionella pneumophila and Helicobacter pylori have been shown to be secreted, immunogenic, and interact with the human host. The surface exposure of vHiSLR, architecture, putative antigenic nature and characteristics of orthologues of vHiSLR lead us to hypothesis that vHiSLR proteins are virulence factors that are exposed to the host, thus playing an important role in infection. |