My laboratory is now leveraging our success with the studies of transporters in Haemophilus influenzae to attack a critically important ABC transporter from non-typeable H. influenza (NTHI). As a pathogen, NTHI colonizes the human respiratory tract. Once the body senses a pathogen, one line of defense is for the host to produce molecules as part of its “innate defense system” that can kill the pathogen or weaken its effect. One such class of defense molecules is antimicrobial peptides (AMPs), which kill bacteria by rupturing their outer cell wall. NTHI use an ABC transporter, known as Sap, for its sensitivity to antimicrobial peptides to transport AMPs into the cell and then degrade the AMPs, which can no longer harm the bacteria. NTHI’s ability to destroy AMPs means that the bacteria proliferate in the respiratory tract of humans, resulting in middle ear inflammation and causing chronic obstructive pulmonary diseases.
What is most interesting about the Sap importer is its dual role in transport. In the nasal cavity, NTHI co-exists with its host without injury and uses the Sap transporter to transport heme, a necessary nutrient. For immunocompromised patients, NTHI travels to the ear canal and uses the same Sap transporter to transport the AMPs. Importers that transport multiple and structurally diverse substrates have not been structurally studied or biochemically classified, which opens up a new area of research in the transporter field and poses new and interesting questions.