Interaction of Mycobacterium leprae with Human Airway Epithelial Cells: Adherence, Entry, Survival, and Identification of Potential Adhesins by Surface Proteome Analysis

Abstract

ABSTRACTThis study examined thein vitrointeraction betweenMycobacterium leprae, the causative agent of leprosy, and human alveolar and nasal epithelial cells, demonstrating thatM. lepraecan enter both cell types and that both are capable of sustaining bacterial survival. Moreover, delivery ofM. lepraeto the nasal septum of mice resulted in macrophage and epithelial cell infection in the lung tissue, sustaining the idea that the airways constitute an importantM. lepraeentry route into the human body. Since critical aspects in understanding the mechanisms of infection are the identification and characterization of the adhesins involved in pathogen-host cell interaction, the nude mouse-derivedM. lepraecell surface-exposed proteome was studied to uncover potentially relevant adhesin candidates. A total of 279 cell surface-exposed proteins were identified based on selective biotinylation, streptavidin-affinity purification, and shotgun mass spectrometry; 11 of those proteins have been previously described as potential adhesins.In vitroassays with the recombinant forms of the histone-like protein (Hlp) and the heparin-binding hemagglutinin (HBHA), considered to be major mycobacterial adhesins, confirmed their capacity to promote bacterial attachment to epithelial cells. Taking our data together, they suggest that the airway epithelium may act as a reservoir and/or portal of entry forM. lepraein humans. Moreover, our report sheds light on the potentially critical adhesins involved inM. leprae-epithelial cell interaction that may be useful in designing more effective tools for leprosy control.