Oxidative Stress and Immunological Complexities in Multidrug-Resistant Tuberculosis

© Springer Nature Singapore Pte Ltd. 2020. Mycobacterium tuberculosis (Mtb), the causitive agent of Tuberculosis (TB) is the leading cause of infection. The infection is caused by aerosols and infects the alveolar macrophage. The lungs counteract against the infection by the antioxidant system in response to the oxidative stress (OS) caused. Mycobacteriumstimulates the lung macrophage to produce reactive oxygen species (ROS). Furthermore, the treatment involves long term multiple drug regimens resulting in poor patient compliance leading to multidrug resistance (MDR-TB). The different first-line and second-line antibiotics are administered in an inactive form which gets converted into the active form by the OS response system of the host and the Mtb. Mtb alters the redox balance via mycolic acid, NADH/NAD+ ratio, and antioxidant enzymes in response to stress. In the following chapter, we have discussed the role of oxidative stress in the host and the pathogen along with the immunological complexities and the genetic modifications resulting in multidrug-resistant tuberculosis. It also discusses the different strategies to target the Mtb infection

Oxidative stress and immunological complexities in multidrug-resistant tuberculosis

Mycobacterium tuberculosis (Mtb), the causitive agent of Tuberculosis (TB) is the leading cause of infection. The infection is caused by aerosols and infects the alveolar macrophage. The lungs counteract against the infection by the antioxidant system in response to the oxidative stress (OS) caused. Mycobacteriumstimulates the lung macrophage to produce reactive oxygen species (ROS). Furthermore, the treatment involves long term multiple drug regimens resulting in poor patient compliance leading to multidrug resistance (MDR-TB). The different first-line and second-line antibiotics are administered in an inactive form which gets converted into the active form by the OS response system of the host and the Mtb. Mtb alters the redox balance via mycolic acid, NADH/NAD+ ratio, and antioxidant enzymes in response to stress. In the following chapter, we have discussed the role of oxidative stress in the host and the pathogen along with the immunological complexities and the genetic modifications resulting in multidrug-resistant tuberculosis. It also discusses the different strategies to target the Mtb infection.</p

Ecology and evolution of Mycobacterium tuberculosis

Tuberculosis (TB) is the number one cause of human death due to an infectious disease. The causative agents of TB are a group of closely related bacteria known as the Mycobacterium tuberculosis complex (MTBC). As the MTBC exhibits a clonal population structure with low DNA sequence diversity, methods (such as multilocus sequence typing) that are applied to more genetically diverse bacteria are uninformative, and much of the ecology and evolution of the MTBC has therefore remained unknown. Owing to recent advances in whole-genome sequencing and analyses of large collections of MTBC clinical isolates from around the world, many new insights have been gained, including a better understanding of the origin of the MTBC as an obligate pathogen and its molecular evolution and population genetic characteristics both within and between hosts, as well as many aspects related to antibiotic resistance. The purpose of this Review is to summarize these recent discoveries and discuss their relevance for developing better tools and strategies to control TB

The nature and evolution of genomic diversity in the Mycobacterium tuberculosis complex

The Mycobacterium tuberculosis Complex (MTBC) consists of a clonal group of several mycobacterial lineages pathogenic to a range of different mammalian hosts. In this chapter, we discuss the origins and the evolutionary forces shaping the genomic diversity of the human-adapted MTBC. Advances in whole-genome sequencing have brought invaluable insights into the macro-evolution of the MTBC, and the biogeographical distribution of the different MTBC lineages, the phylogenetic relationships between these lineages. Moreover, micro-evolutionary processes start to be better understood, including those influencing bacterial mutation rates and those governing the fate of new mutations emerging within patients during treatment. Current genomic and epidemiological evidence reflect the fact that, through ecological specialization, the MTBC affecting humans became an obligate and extremely well-adapted human pathogen. Identifying the adaptive traits of human-adapted MTBC and unraveling the bacterial loci that interact with human genomic variation might help identify new targets for developing better vaccines and designing more effective treatments