title: Mycobacterial Dormancy Systems and Host Responses in Tuberculosis.
abstract: Tuberculosis (TB) caused by the intracellular pathogen,Mycobacterium tuberculosis(Mtb), claims more than 1.5 million lives worldwide annually. Despite promulgation of multipronged strategies to prevent and control TB, there is no significant downfall occurring in the number of new cases, and adding to this is the relapse of the disease due to the emergence of antibiotic resistance and the ability ofMtbto remain dormant after primary infection. The pathology ofMtbis complex and largely attributed to immune-evading strategies that this pathogen adopts to establish primary infection, its persistence in the host, and reactivation of pathogenicity under favorable conditions. In this review, we present various biochemical, immunological, and genetic strategies unleashed byMtbinside the host for its survival. The bacterium enables itself to establish a niche by evading immune recognitionviaresorting to masking, establishment of dormancy by manipulating immune receptor responses, altering innate immune cell fate, enhancing granuloma formation, and developing antibiotic tolerance. Besides these, the regulatory entities, such as DosR and its regulon, encompassing various putative effector proteins play a vital role in maintaining the dormant nature of this pathogen. Further, reactivation ofMtballows relapse of the disease and is favored by the genes of the Rtf family and the conditions that suppress the immune system of the host. Identification of target genes and characterizing the function of their respective antigens involved in primary infection, dormancy, and reactivation would likely provide vital clues to design novel drugs and/or vaccines for the control of dormant TB.
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad , Hyderabad , India.
authors.forename: Vidyullatha
authors.initials: V
authors.lastname: Peddireddy
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad , Hyderabad , India.
authors.forename: Sankara Narayana
authors.initials: SN
authors.lastname: Doddam
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, India; Laboratory Sciences and Services Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmed
keywords: DosR regulon; Mycobacterium tuberculosis; alveolar macrophages; antibiotic resistance; dormancy; granuloma; latency