title: Putative roles of a proline-glutamic acid-rich protein (PE3) in intracellular survival and as a candidate for subunit vaccine against Mycobacterium tuberculosis.
abstract: The proline-glutamic acid (PE) protein family of Mycobacterium tuberculosis (Mtb) plays diverse roles in the pathogenesis and modulation of host immune responses. The uniqueness of conserved regions of PE proteins may be useful to test and validate their corresponding functions. Hence, the present study has been undertaken to demonstrate the role of PE3 (Rv0159c) for persistence, host immune response and immunoprophylaxis. We have expressed Mtb-specific PE3 gene in M. smegmatis (MS) and used the strain to infect J774A.1 macrophage cells and BALB/c mice. It was observed that during the infection, the MS expressing PE3 showed higher bacterial load when compared to infection with wild-type MS. In hypoxic condition, the expression level of PE3 gene was induced in Mtb, which further showed its relevance in the cell survival during hypoxia-induced persistence. The expression level of PE3 in Mtb was markedly induced during chronic stage of murine infection, which reiterated its importance in mycobacterial persistence in the host. The immunization of mice with recombinant PE3 protein stimulated the secretion of TNF, IL-6 and IL-2 cytokines and generated strong protective immunity against challenge with live mycobacteria, which was evidenced by decreased viable bacilli in the lungs, histopathological changes and increased survival of PE3 immunized mice. Conclusively, the results indicated that PE3 plays significant roles in mycobacterial persistence during infection, modulate host immune response and hence could be a prospective candidate for the development of subunit vaccine against tuberculosis.
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226 021, India.
authors.forename: Susmita K
authors.initials: SK
authors.lastname: Singh
authors.forename: Ruma
authors.initials: R
authors.lastname: Kumari
authors.forename: Diwakar K
authors.initials: DK
authors.lastname: Singh
authors.forename: Sameer
authors.initials: S
authors.lastname: Tiwari
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Singh
authors.forename: Sharad
authors.initials: S
authors.lastname: Sharma
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009164:Mycobacterium Infections / Q000276:immunology / Q000517:prevention & control; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic