Immunotherapy With 5, 15-DPP Mediates Macrophage M1 Polarization and Modulates Subsequent Infectivity in rBCG30 Immunized Mice.

Tuberculosis (TB) is a significant and continuing problem worldwide, with a death toll of around 1.5 million human lives annually. BCG, the only vaccine against TB, offers a varied degree of protection among human subjects in different regions and races of the world.

Bacillus calmette-guerin as a quick and temporary solution to coronavirus disease-2019.

The coronavirus disease-2019 (COVID-19) pandemic is one of the most devastating things that happened in the world which has taken the lives of millions of people and has brutally shattered the world economy. This pandemic has instigated an urgent need for a vaccine to reduce the ongoing morbidity and mortality. Bacillus Calmette-Guerin (BCG) apart from being used as an effective and old vaccine against tuberculosis has some known off-target protection effect and is getting more attention in this scenario.

Targeted Pulmonary Delivery of the Green Tea Polyphenol Epigallocatechin Gallate Controls the Growth of by Enhancing the Autophagy and Suppressing Bacterial Burden.

Growing rates of tuberculosis (TB) superbugs are alarming, which has hampered the progress made to-date to control this infectious disease, and new drug candidates are few. Epigallocatechin gallate (EGCG), a major polyphenolic compound from green tea extract, shows powerful efficacy against TB bacteria in studies. However, the therapeutic efficacy of the molecule is limited due to poor pharmacokinetics and low bioavailability following oral administration.

Double deletion of PknI/DacB2 leads to attenuation of Mycobacterium tuberculosis for growth and virulence.

Serine/Threonine Protein Kinases (STPKs) phosphorylates target proteins thereby regulates various important cellular signal transduction pathways such as cell division and cell wall synthesis. It has been demonstrated that the STPKs regulate peptidoglycan biosynthesis by phosphorylating penicillin binding proteins (PBPs). We extensively characterized both PknI (STPK) and DacB2 (PBP) roles individually as well as combining by genetic knockout and phenotypic characterization studies.

Impact and prognosis of the expression of IFN-α among tuberculosis patients.

Mycobacterium tuberculosis (M.tb) infection stimulates the release of cytokines, including interferons (IFNs). IFNs are initiators, regulators, and effectors of innate and adaptive immunity.

Dynamic mucus penetrating microspheres for efficient pulmonary delivery and enhanced efficacy of host defence peptide (HDP) in experimental tuberculosis.

Pulmonary drug delivery system is increasingly gaining popularity for several lung diseases including tuberculosis(TB) due to its ability to attain high drug concentrations at the site of infection and to minimize systemic toxicity. In TB therapy, the efficacy of the antibiotics decreases and bacteria becomes resistant in course of time due to the formation of several barriers like lung-mucus and biofilms around the microorganism. The conventional inhalable microparticles(MP) are majorly trapped in dense mucin mess network and quickly cleared by mucocilliary clearance.

Phosphatase-defective DevS sensor kinase mutants permit constitutive expression of DevR-regulated dormancy genes in Mycobacterium tuberculosis.

The DevR-DevS/DosR-DosS two-component system of Mycobacterium tuberculosis, that comprises of DevS sensor kinase and DevR response regulator, is essential for bacterial adaptation to hypoxia by inducing dormancy regulon expression. The dominant phosphatase activity of DevS under aerobic conditions enables tight negative control, whereas its kinase function activates DevR under hypoxia to induce the dormancy regulon. A net balance in these opposing kinase and phosphatase activities of DevS calibrates the response output of DevR.

Multiple strain infection of Mycobacterium leprae in a family having 4 patients: A study employing short tandem repeats.

Background: Leprosy is a slow, chronic disorder caused by Mycobacterium leprae. India has achieved elimination of leprosy in December 2005 but new cases are being detected and continue to occur in some endemic pockets. The possible ways of transmission of leprosy is not fully understood and is believed that leprosy is transmitted from person to person in long term contact.

Mycobactericidal activity of some micro-encapsulated synthetic Host Defense Peptides (HDP) by expediting the permeation of antibiotic: A new paradigm of drug delivery for tuberculosis.

Resistance to anti-Tuberculosis (anti-TB) drugs is primarily due to unique intrinsic resistance mechanisms that mycobacterium possess. The most important determinant of resistance is a peculiar hydrophobic and multi-layered mycobacterial cell-wall structure with mycolic-acid and wax-D, which restricts permeability of both hydrophobic and hydrophilic drugs into bacteria. In this study, it was supposed that Host Defense peptides (HDP) which are known to permeabilize bacterial membranes may, therefore, help anti-TB antibiotics to target internal sites in bacteria.

Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study.

Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains.

Evaluation of Aggregated Ag85B Antigen for Its Biophysical Properties, Immunogenicity, and Vaccination Potential in a Murine Model of Tuberculosis Infection.

Protein aggregates have been reported to act as a reservoir that can release biologically active, native form of precursor protein. Keeping this fact into consideration, it is tempting to exploit protein aggregate-based antigen delivery system as a functional vaccine to expand desirable immunological response in the host. Herein, we explored the capacity of aggregated Ag85B of () to act as a prophylactic vaccine system that releases the precursor antigen in slow and sustained manner.

Reclaiming hijacked phagosomes: Hybrid nano-in-micro encapsulated MIAP peptide ensures host directed therapy by specifically augmenting phagosome-maturation and apoptosis in TB infected macrophage cells.

TB-Superbugs have emerged as one of the most challenging global health threat due to the decrease in effectiveness of conventional antibiotics. Meanwhile, Host defense peptides (HDP) have evolved as an alternative to classical therapeutics with lesser susceptibility of resistance. We describe the potential of nano-encapsulated synthetic Magainin-I analog peptide (MIAP) as Host Directed Therapy against TB.

Assessment of vocation of rifabutin and rifapentine in replace of rifampcin in drug resistance leprosy patients: a molecular simulation study.

The emergence of drug resistance in leprosy is a major hurdle in leprosy elimination programme. Although the problem of drug resistance is presently not acute, it is important that we collect data more systematically and monitor the trend carefully so that effective measures to combat this problem can be developed. The present study aimed at the explication of cross resistance of rifabutin and rifapentine to rifampicin which would be helpful to programme managers for implementing rifabutin or rifapentine in replace of rifampicin.

Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection.

Background & Objectives: Central nervous system (CNS) infection caused by Mycobacterium tuberculosis (MTB) is the most severe form of extrapulmonary tuberculosis (EPTB) due to a high level of mortality and morbidity. Limited studies are available on CNS-TB animal model development. The present study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients.

Sustained expression of DevR/DosR during long-term hypoxic culture of Mycobacterium tuberculosis.

DevR/DosR is a key mediator of 'dormancy' adaptation in Mycobacterium tuberculosis in response to gaseous stresses such as hypoxia that inhibit aerobic mode of respiration. In the present study, a temporal analysis over a 1 year period has revealed robust expression of representative DevR regulon genes devR, hspX and tgs1, during long-term 'dormancy' adaptation to hypoxia. Notably, a predominant proportion of long-term hypoxia-adapted bacteria were characterized by their inability to grow on solid media, accumulation of triacylglycerols and recovery of growth in liquid media.

Challenges beyond elimination in leprosy.

Every year >200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. The World Health Organization has set a target to interrupt the transmission of leprosy globally by 2020.

Importance of the α10 helix for DevR activation: A road map for screening inhibitors against DevR-mediated dormancy of Mycobacterium tuberculosis.

Objective/background: Bacterial persistence is the hallmark of tuberculosis (TB) and poses the biggest threat to the success of any antitubercular drug regimen. The DevR/DosR dormancy regulator of Mycobacterium tuberculosis belongs to the NarL subfamily of response regulators and is essential for M. tuberculosis persistence in macaque models of TB.

Murine model of TB meningitis.

Background: Central nervous system (CNS) infections caused by Mycobacterium tuberculosis (MTB) are the most severe forms of extrapulmonary TB (EPTB) due to high levels of mortality and neurological morbidity. Limited studies are available on CNS-TB animal-model development, despite the steady rise in cerebral-TB cases in India over the past decade. This study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients.

Chemotherapeutic Evaluation of Guar Gum Coated Chitosan Nanoparticle Against Experimental Tuberculosis.

The major goal of the current research was to develop and evaluate the therapeutic potential of anti-tubercular drugs (ATDs) loaded natural polysaccharide comprising of galacto mannan subunit in experimental tuberculosis (TB). Experimental formulations were prepared by ionotropic gelation technique followed by spray drying. Morphological analysis suggested that optimized nanoparticles were found to be discrete and spherical in nature with a particle size distribution range from 230 ± 4.

Preparation and Preclinical Evaluation of Inhalable Particles Containing Rapamycin and Anti-Tuberculosis Agents for Induction of Autophagy.

Purpose: Mycobacterium tuberculosis (Mtb) inhibits host defense mechanisms, including autophagy. We investigated particles containing rapamycin (RAP) alone or in combination with isoniazid (INH) and rifabutin (RFB) for: targeting lung macrophages on inhalation; inducing autophagy; and killing macrophage-resident Mtb and/or augmenting anti-tuberculosis (TB) drugs.

Methods: PLGA and drugs were spray-dried.

The α10 helix of DevR, the Mycobacterium tuberculosis dormancy response regulator, regulates its DNA binding and activity.

The crystal structures of several bacterial response regulators provide insight into the various interdomain molecular interactions potentially involved in maintaining their 'active' or 'inactive' states. However, the requirement of high concentrations of protein, an optimal pH and ionic strength buffers during crystallization may result in a structure somewhat different from that observed in solution. Therefore, functional assessment of the physiological relevance of the crystal structure data is imperative.

Improved protection against tuberculosis after boosting the BCG-primed mice with subunit Ag 85a delivered through intact skin with deformable vesicles.

To improve vaccination against tuberculosis (TBC) with Bacillus Calmette-Guerin (BCG), we introduce novel, non-invasive, secondary immunisations relying on epicutaneous (e.c.) applications of the TBC subunit antigen, Ag 85a, associated with deformable carrier vesicles.

Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis.

The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations.