title: The allele encoding the mycobacterial Erp protein affects lung disease in mice.
abstract: Erp (exported repetitive protein), also known as P36, Pirg and Rv3810, is a member of a mycobacteria-specific family of extracellular proteins. These proteins consist of three domains, the N- and C-terminal domains are similar in all mycobacterial species, however, the central domain contains a repeated PGLTS module and differs considerably between species. The erp knockout mutant of Mycobacterium tuberculosis displays very low levels of multiplication both in macrophage cell lines and in vivo in a mouse model of infection. The high interspecies variability of the central repeated region of the Erp protein led us to investigate whether these orthologous proteins were functionally equivalent in a mouse model of tuberculosis. We expressed a gene fusion with the erp gene of Mycobacterium smegmatis, Mycobacterium leprae or M. tuberculosis in trans in an erp-M. tuberculosis mutant and found that these three alleles restored multiplication to similar levels in the spleen of infected mice. However, these alleles gave different levels of colonization in the lung, for the early time-points. Quantitative histological analyses of the lungs of infected animals showed that the nature of the erp allele strongly affected the number and the size of lung lesions, demonstrating the importance of surface determinants for virulence and tissue damage.
authors.affiliation: Unité de Génétique Mycobactérienne, and Plateau technique, Puces à ADN, Institut Pasteur, Paris, France.
authors.forename: Leila
authors.initials: L
authors.lastname: de Mendonça-Lima
authors.forename: Yann
authors.initials: Y
authors.lastname: Bordat
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pivert
authors.forename: Chiara
authors.initials: C
authors.lastname: Recchi
authors.forename: Olivier
authors.initials: O
authors.lastname: Neyrolles
authors.forename: Aboubakar
authors.initials: A
authors.lastname: Maitournam
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reyrat
mesh_terms: D000483:Alleles; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology* / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; C096737:ERP protein, Mycobacterium tuberculosis; D008565:Membrane Proteins