1,640 results match your criteria host mtb

Regulatory Mechanisms of Autophagy-Targeted Antimicrobial Therapeutics Against Mycobacterial Infection.

Front Cell Infect Microbiol 2021 22;11:633360. Epub 2021 Mar 22.

Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea.

(Mtb) is an intracellular pathogen causing human tuberculosis, an infectious disease that still remains as a global health problem. Autophagy, a lysosomal degradative process, has emerged as a critical pathway to restrict intracellular Mtb growth through enhancement of phagosomal maturation. Indeed, several autophagy-modulating agents show promise as host-directed therapeutics for Mtb infection. Read More

View Article and Full-Text PDF

Enzymatic β-Oxidation of the Cholesterol Side Chain in Bifurcates Stereospecifically at Hydration of 3-Oxo-cholest-4,22-dien-24-oyl-CoA.

ACS Infect Dis 2021 Apr 7. Epub 2021 Apr 7.

Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.

The unique ability of (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development. Herein, we identify and characterize two genes from the Cho-region (genomic locus responsible for cholesterol catabolism) of the Mtb genome, (Rv3538) and (Rv3502c). Their protein products catalyze two sequential stereospecific hydration and dehydrogenation steps in the β-oxidation of the cholesterol side chain. Read More

View Article and Full-Text PDF

From infection niche to therapeutic target: the intracellular lifestyle of .

Microbiology (Reading) 2021 Apr;167(4)

Department of Microbiology & Immunology, The University of British Columbia, Vancouver, Canada.

(Mtb) is an obligate human pathogen killing millions of people annually. Treatment for tuberculosis is lengthy and complicated, involving multiple drugs and often resulting in serious side effects and non-compliance. Mtb has developed numerous complex mechanisms enabling it to not only survive but replicate inside professional phagocytes. Read More

View Article and Full-Text PDF

Computational evaluation of anticipated PE_PGRS39 protein involvement in host-pathogen interplay and its integration into vaccine development.

3 Biotech 2021 Apr 1;11(4):204. Epub 2021 Apr 1.

Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007 India.

causes more than 1 million deaths every year, which is higher than any other bacterial pathogen. Its success depends on its interaction with the host and its ability to regulate the host's immune system for its own survival. HRv (Mtb) proteome consists of unique PE_PGRS family proteins, which present a significant role in bacterial pathogenesis over the past years. Read More

View Article and Full-Text PDF

Omega-3 long-chain polyunsaturated fatty acids promote antibacterial and inflammation-resolving effects in -infected C3HeB/FeJ mice, dependent on fatty acid status.

Br J Nutr 2021 Apr 5:1-35. Epub 2021 Apr 5.

Centre of Excellence for Nutrition, North-West University, Potchefstroom, North West, South Africa, 2531.

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Read More

View Article and Full-Text PDF

Advances in host-based screening for compounds with intracellular anti-mycobacterial activity.

Cell Microbiol 2021 Apr 4:e13337. Epub 2021 Apr 4.

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India.

Intracellular pathogens interact with host systems in intimate ways to sustain a pathogenic lifestyle. Consequently, these interactions can potentially be targets of host directed interventions against infectious diseases. In case of tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), while effective anti-tubercular compounds are available, the long treatment duration and emerging drug resistance necessitate identification of new class of molecules with anti-TB activity, as well as new treatment strategies. Read More

View Article and Full-Text PDF

Immunomodulation by epigenome alterations in Mycobacterium tuberculosis infection.

Tuberculosis (Edinb) 2021 Mar 12;128:102077. Epub 2021 Mar 12.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005, India. Electronic address:

Mycobacterium tuberculosis (MTB) has co-evolved with humans for decades and developed several mechanisms to evade host immunity. It can efficiently alter the host epigenome, thus playing a major role in immunomodulation by either activating or suppressing genes responsible for mounting an immune response against the pathogen. Epigenetic modifications such as DNA methylation and chromatin remodelling regulate gene expression and influence several cellular processes. Read More

View Article and Full-Text PDF

Load in Host Cells and the Antibacterial Activity of Alveolar Macrophages Are Linked and Differentially Regulated in Various Lung Lesions of Patients with Pulmonary Tuberculosis.

Int J Mol Sci 2021 Mar 26;22(7). Epub 2021 Mar 26.

Scientific Department, Ural Research Institute for Phthisiopulmonology, National Medical Research Center of Tuberculosis and Infectious Diseases of Ministry of Health of the Russian Federation, 50 XXII Partsyezda Street, 620039 Yekaterinburg, Russia.

Tuberculosis (TB) is a disease caused by () infection with the formation of a broad range of abnormal lung lesions within a single patient. Although host-pathogen interactions determine disease outcome, they are poorly understood within individual lesions at different stages of maturation. We compared load in a tuberculoma wall and the lung tissue distant from tuberculomas in TB patients. Read More

View Article and Full-Text PDF

Understanding Metabolic Regulation Between Host and Pathogens: New Opportunities for the Development of Improved Therapeutic Strategies Against Infection.

Front Cell Infect Microbiol 2021 16;11:635335. Epub 2021 Mar 16.

Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 Project for Graduate School of Medical Science, Yonsei University College of Medicine, Seoul, South Korea.

(Mtb) causes chronic granulomatous lung disease in humans. Recently, novel strategies such as host-directed therapeutics and adjunctive therapies that enhance the effect of existing antibiotics have emerged to better control Mtb infection. Recent advances in understanding the metabolic interplay between host immune cells and pathogens have provided new insights into how their interactions ultimately influence disease outcomes and antibiotic-treatment efficacy. Read More

View Article and Full-Text PDF

One Size Fits All? Not in Modeling of Tuberculosis Chemotherapeutics.

Front Cell Infect Microbiol 2021 16;11:613149. Epub 2021 Mar 16.

Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.

Tuberculosis (TB) remains a global health problem despite almost universal efforts to provide patients with highly effective chemotherapy, in part, because many infected individuals are not diagnosed and treated, others do not complete treatment, and a small proportion harbor ) strains that have become resistant to drugs in the standard regimen. Development and approval of new drugs for TB have accelerated in the last 10 years, but more drugs are needed due to both 's development of resistance and the desire to shorten therapy to 4 months or less. The drug development process needs predictive animal models that recapitulate the complex pathology and bacterial burden distribution of human disease. Read More

View Article and Full-Text PDF

De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation.

Commun Biol 2021 Mar 25;4(1):410. Epub 2021 Mar 25.

National Institute of Immunology, New Delhi, India.

Intracellular pathogens including Mycobacterium tuberculosis (Mtb) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However, Mtb also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does Mtb meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. Read More

View Article and Full-Text PDF

PE_PGRS3 ensures provision of the vital phospholipids cardiolipin and phosphatidylinositols by promoting the interaction between and host cells.

Virulence 2021 Dec;12(1):868-884

Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario "A. Gemelli", Rome, Italy.

PE_PGRS proteins of () constitute a large family of complex modular proteins whose role is still unclear. Among those, we have previously shown, using the heterologous expression in , that PE_PGRS3 containing a unique arginine-rich C-terminal domain, promotes adhesion to host cells. In this study, we investigate the role of PE_PGRS3 and its C-terminal domain directly in using functional deletion mutants. Read More

View Article and Full-Text PDF
December 2021

Proteomic analysis of drug-susceptible and multidrug-resistant nonreplicating Beijing strains of cultured .

Biochem Biophys Rep 2021 Jul 9;26:100960. Epub 2021 Mar 9.

Department of Microbiology and Research and Diagnostic Center for Emerging Infectious Diseases (RCEID), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

The existence of latent tuberculosis infection (LTBI) is one of the main obstacles hindering eradication of tuberculosis (TB). To better understand molecular mechanisms and explore biomarkers for the pathogen during LTBI, we cultured strains of () under stress conditions, mimicking those in the host granuloma intracellular environment, to induce entry into the non-replicating persistence stage. The stresses included hypoxia, low pH (5. Read More

View Article and Full-Text PDF

Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-1/Mtb Co-infected Persons.

Front Immunol 2021 5;12:645446. Epub 2021 Mar 5.

Tuberculosis Laboratory, The Francis Crick Institute, London, United Kingdom.

Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV-1 co-infected persons. In order to understand host immune responses during ART in the context of (Mtb) sensitization, we performed RNAseq analysis of whole blood-derived RNA from individuals with latent TB infection coinfected with HIV-1, during the first 6 months of ART. A significant fall in RNA sequence abundance of the Hallmark IFN-alpha, IFN-gamma, IL-6/JAK/STAT3 signaling, and inflammatory response pathway genes indicated reduced immune activation and inflammation at 6 months of ART compared to day 0. Read More

View Article and Full-Text PDF

Extracellular vesicles in the context of Mycobacterium tuberculosis infection.

Mol Immunol 2021 May 17;133:175-181. Epub 2021 Mar 17.

Department of Preventive Medicine and Public Health and Microbiology, Autonoma University of Madrid, 28029, Madrid, Spain. Electronic address:

The production of extracellular vesicles (EVs) has emerged as an important process in bacterial biology and host-pathogen interactions. Like many other bacteria, mycobacteria, including Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), produces EVs in vitro and in vivo. These membrane-enclosed nanoparticles enable Mtb to secrete hydrophobic molecules, proteins, lipids and glycolipids in a concentrated and protected manner and engage in remote interactions with the host. Read More

View Article and Full-Text PDF

Compromised base excision repair pathway in Mycobacterium tuberculosis imparts superior adaptability in the host.

PLoS Pathog 2021 Mar 19;17(3):e1009452. Epub 2021 Mar 19.

Signal Transduction Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.

Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is a significant public health concern, exacerbated by the emergence of drug-resistant TB. To combat the host's dynamic environment, Mtb encodes multiple DNA repair enzymes that play a critical role in maintaining genomic integrity. Mtb possesses a GC-rich genome, rendering it highly susceptible to cytosine deaminations, resulting in the occurrence of uracils in the DNA. Read More

View Article and Full-Text PDF

Immunopathogenesis in HIV-associated pediatric tuberculosis.

Pediatr Res 2021 Mar 17. Epub 2021 Mar 17.

Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA, USA.

Tuberculosis (TB) is an increasing global emergency in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients, in which host immunity is dysregulated and compromised. However, the pathogenesis and efficacy of therapeutic strategies in HIV-associated TB in developing infants are essentially lacking. Bacillus Calmette-Guerin vaccine, an attenuated live strain of Mycobacterium bovis, is not adequately effective, which confers partial protection against Mycobacterium tuberculosis (Mtb) in infants when administered at birth. Read More

View Article and Full-Text PDF

Macrophage-specific responses to human- and animal-adapted tubercle bacilli reveal pathogen and host factors driving multinucleated cell formation.

PLoS Pathog 2021 Mar 15;17(3):e1009410. Epub 2021 Mar 15.

The Francis Crick Institute, London, United Kingdom.

The Mycobacterium tuberculosis complex (MTBC) is a group of related pathogens that cause tuberculosis (TB) in mammals. MTBC species are distinguished by their ability to sustain in distinct host populations. While Mycobacterium bovis (Mbv) sustains transmission cycles in cattle and wild animals and causes zoonotic TB, M. Read More

View Article and Full-Text PDF

Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.

Front Cell Infect Microbiol 2021 26;11:624607. Epub 2021 Feb 26.

Metabolism of Infectious Diseases Laboratory, Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.

Infection with (Mtb) leading to tuberculosis (TB) disease continues to be a major global health challenge. Critical barriers, including but not limited to the development of multi-drug resistance, lack of diagnostic assays that detect patients with latent TB, an effective vaccine that prevents Mtb infection, and infectious and non-infectious comorbidities that complicate active TB, continue to hinder progress toward a TB cure. To complement the ongoing development of new antimicrobial drugs, investigators in the field are exploring the value of host-directed therapies (HDTs). Read More

View Article and Full-Text PDF
February 2021

The impact of common Smurf1 gene variants on the risk, clinical characteristics and short-term prognosis of tuberculous meningitis.

Int J Infect Dis 2021 Mar 9. Epub 2021 Mar 9.

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, No.37, Guo Xue Alley, Chengdu, 610041, China. Electronic address:

Objectives: Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis (Mtb). Smurf1 represents a key component in anti-Mtb autophagic targeting in macrophages and in anti-TB host defense in vivo. We hypothesized that genetic variants in the Smurf1 gene region influence susceptibility to TBM. Read More

View Article and Full-Text PDF

TGFβ restricts expansion, survival, and function of T cells within the tuberculous granuloma.

Cell Host Microbe 2021 Mar 5. Epub 2021 Mar 5.

Department of Immunology, University of Washington, Seattle, WA 98109, USA. Electronic address:

CD4 T cell effector function is required for optimal containment of Mycobacterium tuberculosis (Mtb) infection. IFNɣ produced by CD4 T cells is a key cytokine that contributes to protection. However, lung-infiltrating CD4 T cells have a limited ability to produce IFNɣ, and IFNɣ plays a lesser protective role within the lung than at sites of Mtb dissemination. Read More

View Article and Full-Text PDF

Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis.

Nat Commun 2021 03 11;12(1):1606. Epub 2021 Mar 11.

Council of Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh, India.

Tuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. Read More

View Article and Full-Text PDF

Regulation of Mitogen-Activated Protein Kinase Signaling Pathway and Proinflammatory Cytokines by Ursolic Acid in Murine Macrophages Infected with .

Infect Dis Rep 2020 Jul 6;12(11):5-10. Epub 2020 Jul 6.

Department of Pharmacology-Clinical Pharmacy, School of Pharmacy, Institut Teknologi Bandung, Labtek 7, Jl. Ganesha No.10, Lb. Siliwangi, Coblong, Bandung 40132, West Java, Indonesia..

, one of the closest relatives of (MTB), offers an advantage in studying MTB because of its tuberculosis-like effect in humans and host immune tolerance. This study examined the antimycobacterial action of ursolic acid and its regulation in macrophages during infection. Colony-forming units of the bacteria were determined in the cell lysate of macrophages and in the supernatant. Read More

View Article and Full-Text PDF

Association of polymorphisms of innate immunity-related genes and tuberculosis susceptibility in Mongolian population.

Hum Immunol 2021 Mar 7. Epub 2021 Mar 7.

Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China. Electronic address:

Backgrounds: Genetic polymorphism of the toll-like receptor 2, 4 (TLR2, TLR4) and natural resistance-associated macrophage protein 1 (NRAMP1) genes may affect host immune response to Mycobacterium tuberculosis (Mtb) and lead to the variation of susceptibility to tuberculosis (TB) in humans. However, the association of single nucleotide polymorphisms (SNP) in these genes and the susceptibility to TB in Mongolian population has not been investigated.

Methods: We conducted a genetic association study including 197 Mongolian TB patients and 217 Mongolian healthy controls in Inner Mongolia, China. Read More

View Article and Full-Text PDF

Deletion of serine/threonine-protein kinase pknL from Mycobacterium tuberculosis reduces the efficacy of isoniazid and ethambutol.

Tuberculosis (Edinb) 2021 Mar 4;128:102066. Epub 2021 Mar 4.

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India. Electronic address:

Serine/threonine-protein kinases in Mycobacterium tuberculosis (Mtb) form a preeminent regulatory system required to establish and maintain the infection in the host. Herein, we sought to decipher the biological role of PknL with the help of a gene replacement mutant RvΔpknL. Deletion of pknL results in the compromised growth under redox stress. Read More

View Article and Full-Text PDF

B-Cells and Antibodies as Contributors to Effector Immune Responses in Tuberculosis.

Front Immunol 2021 18;12:640168. Epub 2021 Feb 18.

Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.

Tuberculosis (TB), caused by (Mtb), is still a major threat to mankind, urgently requiring improved vaccination and therapeutic strategies to reduce TB-disease burden. Most present vaccination strategies mainly aim to induce cell-mediated immunity (CMI), yet a series of independent studies has shown that B-cells and antibodies (Abs) may contribute significantly to reduce the mycobacterial burden. Although early studies using B-cell knock out animals did not support a major role for B-cells, more recent studies have provided new evidence that B-cells and Abs can contribute significantly to host defense against Mtb. Read More

View Article and Full-Text PDF
February 2021

Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities.

Molecules 2021 Feb 20;26(4). Epub 2021 Feb 20.

Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa.

The cell wall of () has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. Read More

View Article and Full-Text PDF
February 2021

Generation of Liposomes to Study the Effect of Lipids on HIV-1 - and -Infections.

Int J Mol Sci 2021 Feb 16;22(4). Epub 2021 Feb 16.

Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK.

Tuberculosis (TB) is the leading cause of death among HIV-1-infected individuals and () co-infection is an early precipitate to AIDS. We aimed to determine whether strains differentially modulate cellular susceptibility to HIV-1 infection (- and -infection), via surface receptor interaction by their cell envelope lipids. Total lipids from pathogenic (lineage 4 H37Rv, CDC1551 and lineage 2 HN878, EU127) and non-pathogenic ( BCG and ) strains were integrated into liposomes mimicking the lipid distribution and antigen accessibility of the mycobacterial cell wall. Read More

View Article and Full-Text PDF
February 2021

THP1 proteomics in response to infection.

Data Brief 2021 Apr 30;35:106803. Epub 2021 Jan 30.

Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.

Temporal data on how the mycobacterium infection establishes itself inside the host cell is not available. We differentiated human THP1 cell line with PMA and infected them with different laboratory (H37Ra and H37Rv) and clinical strains (BND433 and JAL2287) of mycobacterium tuberculosis (Mtb). Uninfected differentiated THP1 cells were used as infection control. Read More

View Article and Full-Text PDF

Generating Three-dimensional Human Granulomas to Study -Host Interaction.

Bio Protoc 2020 Nov 20;10(22):e3820. Epub 2020 Nov 20.

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Granulomas are organized multicellular structures that constitute the hallmark of an infection by the human pathogen A better understanding of the complex host- interactions within the granuloma's environment may lead to new therapeutic or preventive tools to improve the control of the tuberculosis pandemic. To date, several models that are able to mimic human nascent granulomas have been reported. Here we describe a protocol in which -infected human peripheral blood mononuclear cells (PBMCs) are embedded within a collagen matrix leading to the formation of three-dimensional micro-granulomas. Read More

View Article and Full-Text PDF
November 2020