Mycobacterium tuberculosis Rv0679c protein sequences involved in host-cell infection: potential TB vaccine candidate antigen.
BACKGROUND
To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was studied in 26 Mycobacterium spp. Strains. Antibodies raised against putative B-cell epitopes of Rv0679c were used in Western blot and immunoelectron microscopy assays. Synthetic peptides spanning the entire length of the protein were tested for their ability to bind to A549 and U937 cells. High-activity binding peptides (HABPs) identified in Rv0679c were tested for their ability to inhibit mycobacterial invasion into cells.


RESULTS
The gene encoding Rv0679c was detected in all strains of the M. tuberculosis complex (MTC), but was only transcribed in M. tuberculosis H37Rv, M. tuberculosis H37Ra and M. africanum. Anti-Rv0679c antibodies specifically recognized the protein in M. tuberculosis H37Rv sonicate and showed its localization on mycobacterial surface. Four HABPs inhibited invasion of M. tuberculosis to target cells by up to 75%.


CONCLUSIONS
The results indicate that Rv0679c HABPs and in particular HABP 30979 could be playing an important role during M. tuberculosis invasion of host cells, and therefore could be interesting research targets for studies aimed at developing strategies to control tuberculosis.
Cifuentes
Diana P
DP
Fundación Instituto de Inmunología de Colombia, Carrera 50 No, 26-20, Bogotá, Colombia.
Ocampo
Marisol
M
Curtidor
Hernando
H
Vanegas
Magnolia
M
Forero
Martha
M
Patarroyo
Manuel E
ME
Patarroyo
Manuel A
MA
D000907:Antibodies, Bacterial / Q000302:isolation & purification; D000942:Antigens, Bacterial / Q000276:immunology / Q000502:physiology*; D001426:Bacterial Proteins / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D016253:Microscopy, Immunoelectron; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D011485:Protein Binding; D032581:Tuberculosis Vaccines / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology / Q000502:physiology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D032581:Tuberculosis Vaccines; D037521:Virulence Factors
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