Rv1273c, an ABC transporter of Mycobacterium tuberculosis promotes mycobacterial intracellular survival within macrophages via modulating the host cell immune response

摘要

Mycobacterium proteins, especially cell wall associated proteins, interact with host macrophage to regulate the functions and cytokine production. So, identification and characterization of such proteins is essential for understanding tuberculosis pathogenesis. The role of the ABC transporter proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. In the present study, Rv1273c, an ABC transporter, has been expressed in a non-pathogenic and fast growing Mycobacterium smegmatis strain to explore its role in host pathogen interactions. Over expression of Rv1273c resulted in enhanced intracellular survival in macrophage as well as modified cell wall architecture. We found altered colony morphology and cell surface properties that might be linked with remodelling of bacterial cell wall which may help in the intracellular survival of mycobacterium. However, the enhanced intracellular survival was not found to be the consequence of an increased resistance to intracellular stresses. The activation of macrophage by Rv1273c was associated with perturbed cytokine production. Pharmacological inhibition experiment and western immunoblotting suggested that this altered cytokine profile was mediated possibly by NF-kB and p38 pathway in macrophage. Overall, the present findings indicated that Rv1273c enhanced mycobacterium persistence and mediated the evasion of immune responses during infection. (C) 2019 Elsevier B.V. All rights reserved.