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INTERACTION OF MYCOBACTERIUM LEPRAE WITH HUMAN AIRWAY EPITHELIAL CELLS: ADHERENCE, ENTRY, SURVIVAL, AND IDENTIFICATION OF POTENTIAL ADHESINS BY SURFACE PROTEOME ANALYSIS
Autor
Afiliación
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Corvallis, Oregon, USA.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Corvallis, Oregon, USA.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Molecular and Cellular Biology Program. Corvallis, Oregon, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Corvallis, Oregon, USA.
INRA Centre de Tours. Santé Publique (IASP-311). Infectiologie Animale. Nouzilly, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Rio de Janeiro, RJ, Brasil.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Molecular and Cellular Biology Program. Corvallis, Oregon, USA / Oregon State University. College of Science. Department of Microbiology. Corvallis, Oregon, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Corvallis, Oregon, USA.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Molecular and Cellular Biology Program. Corvallis, Oregon, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Corvallis, Oregon, USA.
INRA Centre de Tours. Santé Publique (IASP-311). Infectiologie Animale. Nouzilly, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Rio de Janeiro, RJ, Brasil.
Oregon State University. College of Veterinary Medicine. Department of Biomedical Sciences. Molecular and Cellular Biology Program. Corvallis, Oregon, USA / Oregon State University. College of Science. Department of Microbiology. Corvallis, Oregon, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Resumen en ingles
This study examined the in vitro interaction between Mycobacterium leprae, the causative agent of leprosy, and human alveolar
and nasal epithelial cells, demonstrating thatM. leprae can enter both cell types and that both are capable of sustaining bacterial
survival. Moreover, delivery of M. leprae to the nasal septum of mice resulted in macrophage and epithelial cell infection in the
lung tissue, sustaining the idea that the airways constitute an important M. leprae entry 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-derived M. leprae cell 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 vitro assays 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 for M.
leprae in humans. Moreover, our report sheds light on the potentially critical adhesins involved in M. leprae-epithelial cell interaction
that may be useful in designing more effective tools for leprosy control.
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