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Frontiers in Cellular and Infection... 2022Mycobacteria are members of the Actinomycetales order, and they are classified into one family, Mycobacteriaceae. More than 20 mycobacterial species cause disease in... (Review)
Review
Mycobacteria are members of the Actinomycetales order, and they are classified into one family, Mycobacteriaceae. More than 20 mycobacterial species cause disease in humans. The Mycobacterium group, called the complex (MTBC), has nine closely related species that cause tuberculosis in animals and humans. TB can be detected worldwide and one-fourth of the world's population is contaminated with tuberculosis. According to the WHO, about two million dies from it, and more than nine million people are newly infected with TB each year. () is the most potential causative agent of tuberculosis and prompts enormous mortality and morbidity worldwide due to the incompletely understood pathogenesis of human tuberculosis. Moreover, modern diagnostic approaches for human tuberculosis are inefficient and have many lacks, while MTBC species can modulate host immune response and escape host immune attacks to sustain in the human body. "Multi-omics" strategies such as genomics, transcriptomics, proteomics, metabolomics, and deep sequencing technologies could be a comprehensive strategy to investigate the pathogenesis of mycobacterial species in humans and offer significant discovery to find out biomarkers at the early stage of disease in the host. Thus, in this review, we attempt to understand an overview of the mission of "omics" approaches in mycobacterial pathogenesis, including tuberculosis, leprosy, and other mycobacterial diseases.
Topics: Animals; Genomics; Humans; Leprosy; Mycobacterium tuberculosis; Proteomics; Tuberculosis
PubMed: 35281437
DOI: 10.3389/fcimb.2022.792617 -
Nature Microbiology Sep 2022
Topics: Mycobacterium abscessus
PubMed: 36008618
DOI: 10.1038/s41564-022-01217-6 -
MBio May 2024Since the discovery of extracellular vesicles (EVs) in mycobacterial species 15 years back, we have learned that this phenomenon is conserved in the genus and has... (Review)
Review
Since the discovery of extracellular vesicles (EVs) in mycobacterial species 15 years back, we have learned that this phenomenon is conserved in the genus and has critical roles in bacterial physiology and host-pathogen interactions. (), the tuberculosis (TB) causative agent, produces EVs both and including a diverse set of biomolecules with demonstrated immunomodulatory effects. Moreover, EVs (MEVs) have been shown to possess vaccine properties and carry biomarkers with diagnostic capacity. Although information on MEV biogenesis relative to other bacterial species is scarce, recent studies have shed light on how MEVs originate and are released to the extracellular space. In this minireview, we discuss past and new information about the vesiculogenesis phenomenon in , including biogenesis, MEV cargo, aspects in the context of host-pathogen interactions, and applications that could help to develop effective tools to tackle the disease.
Topics: Extracellular Vesicles; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Tuberculosis; Animals; Biomarkers; Mycobacterium
PubMed: 38567992
DOI: 10.1128/mbio.02552-23 -
Frontiers in Immunology 2023The induction of an effective immune response is critical for the success of mRNA-based therapeutics. Here, we developed a nanoadjuvant system compromised of Quil-A and...
The induction of an effective immune response is critical for the success of mRNA-based therapeutics. Here, we developed a nanoadjuvant system compromised of Quil-A and DOTAP (dioleoyl 3 trimethylammonium propane), hence named QTAP, for the efficient delivery of mRNA vaccine constructs into cells. Electron microscopy indicated that the complexation of mRNA with QTAP forms nanoparticles with an average size of 75 nm and which have ~90% encapsulation efficiency. The incorporation of pseudouridine-modified mRNA resulted in higher transfection efficiency and protein translation with low cytotoxicity than unmodified mRNA. When QTAP-mRNA or QTAP alone transfected macrophages, pro-inflammatory pathways (e.g., NLRP3, NF-kb, and MyD88) were upregulated, an indication of macrophage activation. In C57Bl/6 mice, QTAP nanovaccines encoding Ag85B and Hsp70 transcripts (QTAP-85B+H70) were able to elicit robust IgG antibody and IFN- ɣ, TNF-α, IL-2, and IL-17 cytokines responses. Following aerosol challenge with a clinical isolate of significant reduction of mycobacterial counts was observed in lungs and spleens of only immunized animals at both 4- and 8-weeks post-challenge. As expected, reduced levels of were associated with diminished histological lesions and robust cell-mediated immunity. Interestingly, polyfunctional T-cells expressing IFN- ɣ, IL-2, and TNF- α were detected at 8 but not 4 weeks post-challenge. Overall, our analysis indicated that QTAP is a highly efficient transfection agent and could improve the immunogenicity of mRNA vaccines against pulmonary , an infection of significant public health importance, especially to the elderly and to those who are immune compromised.
Topics: Animals; Mice; Mycobacterium avium; Mycobacterium tuberculosis; Interleukin-2; RNA; RNA, Messenger
PubMed: 37359562
DOI: 10.3389/fimmu.2023.1188754 -
Saudi Medical Journal Jul 2021To optimize an enzyme-linked immunosorbent assay (ELISA) for measuring the HspX protein (α-crystallin) levels and then evaluate its correlation with the accumulation of...
OBJECTIVES
To optimize an enzyme-linked immunosorbent assay (ELISA) for measuring the HspX protein (α-crystallin) levels and then evaluate its correlation with the accumulation of lipid bodies in ( during hypoxia and exposure to nitric oxide.
METHODS
This study was conducted at Prince Sultan Military Medical City, Riyadh, Saudi Arabia between 2016 and 2017. We first optimized ELISA conditions for the detection of HspX. The optimization protocol focused on minimizing concentrations of the capture antibody, detection antibody, and conjugated secondary antibody, and determining the minimum detection limit of the antigen, HspX. Bacteria were grown either in shaking culture or in stationary flasks mimicking hypoxic environments. A standard Bradford assay was used to determine the total protein and HspX was detected using the optimized ELISA protocol. The effect of hypoxic environment and nitric oxide on the levels of HspX and lipid bodies, detected by staining with Nile red, was also evaluated.
RESULTS
An optimized ELISA protocol was established for the detection of HspX from . Exposure to nitric oxide and hypoxic conditions led to an increase in the levels of HspX protein. The increase in HspX associated with nitric oxide treatment and hypoxic conditions correlated with higher levels of lipid bodies mainly found in pathogenic mycobacteria.
CONCLUSIONS
The optimized ELISA protocol in this study can detect HspX protein levels in growing in normal and hypoxic environments. Importantly, hypoxia led to enhanced expression of HspX protein, which correlated with the enhanced production of lipid bodies. Lipid body production is a survival strategy of pathogenic mycobacteria.
Topics: Antigens, Bacterial; Bacterial Proteins; Enzyme-Linked Immunosorbent Assay; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Saudi Arabia
PubMed: 34187915
DOI: 10.15537/smj.2021.42.7.20200582 -
Current Medicinal Chemistry 2020Ranking above AIDS, Tuberculosis (TB) is the ninth leading cause of death affecting and killing many individuals every year. Drugs' efficacy is limited by a series of...
Ranking above AIDS, Tuberculosis (TB) is the ninth leading cause of death affecting and killing many individuals every year. Drugs' efficacy is limited by a series of problems such as Multi- Drug Resistance (MDR) and Extensively-Drug Resistance (XDR). Meanwhile, the only licensed vaccine BCG (Bacillus Calmette-Guérin) existing for over 90 years is not effective enough. Consequently, it is essential to develop novel vaccines for TB prevention and immunotherapy. This paper provides an overall review of the TB prevalence, immune system response against TB and recent progress of TB vaccine research and development. Several vaccines in clinical trials are described as well as LAM-based candidates.
Topics: BCG Vaccine; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines
PubMed: 30474525
DOI: 10.2174/0929867326666181126112124 -
Nature Microbiology Apr 2023Mycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the...
Mycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the molecular details of phage infection and mechanisms of resistance remain ill-defined. Here we use live-cell fluorescence microscopy to visualize the spatiotemporal dynamics of mycobacteriophage infection in single cells and populations, showing that infection is dependent on the host nucleoid-associated Lsr2 protein. Mycobacteriophages preferentially adsorb at Mycobacterium smegmatis sites of new cell wall synthesis and following DNA injection, Lsr2 reorganizes away from host replication foci to establish zones of phage DNA replication (ZOPR). Cells lacking Lsr2 proceed through to cell lysis when infected but fail to generate consecutive phage bursts that trigger epidemic spread of phage particles to neighbouring cells. Many mycobacteriophages code for their own Lsr2-related proteins, and although their roles are unknown, they do not rescue the loss of host Lsr2.
Topics: Mycobacteriophages; Mycobacterium; Mycobacterium smegmatis; Bacteriophages
PubMed: 36823286
DOI: 10.1038/s41564-023-01333-x -
Infection Jun 2023
Topics: Humans; Abscess; Mycobacterium; Muscles; Nontuberculous Mycobacteria
PubMed: 36472781
DOI: 10.1007/s15010-022-01961-1 -
International Journal of Molecular... Mar 2022Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization,... (Review)
Review
Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization, lifestyle changes and new technologies in the animal and plant industry are involved in frequent contact of people with mycobacteria. Type 1 diabetes is a multifactorial polygenic disease; its origin is conditioned by the mutual interaction of genetic and other factors. The environmental factors and certain pathogenetic pathways are shared by some immune mediated chronic inflammatory and autoimmune diseases, which are associated with triggers originating mainly from subspecies , an intestinal pathogen which persists in the environment. Type 1 diabetes and some other chronic inflammatory diseases thus pose the global health problem which could be mitigated by measures aimed to decrease the human exposure to this neglected zoonotic mycobacterium.
Topics: Animals; Diabetes Mellitus, Type 1; Humans; Intestines; Mycobacterium; Mycobacterium avium subsp. paratuberculosis; Paratuberculosis
PubMed: 35409018
DOI: 10.3390/ijms23073657 -
Bulletin of Experimental Biology and... Jan 2023We evaluated the vaccine properties of a novel attenuated strain of M. tuberculosis BN (Mtb BN) and its impact on the gut microbiota in inbred female mice in comparison...
We evaluated the vaccine properties of a novel attenuated strain of M. tuberculosis BN (Mtb BN) and its impact on the gut microbiota in inbred female mice in comparison with a virulent strain Mtb H37Rv and a vaccine strain BCG. The Mtb BN strain demonstrated the highest anti-tuberculosis vaccine effect in I/St mice highly susceptible to tuberculosis infection and the same effect as BCG in mice of the recombinant strain B6.I-100 and in β2 microglobulin gene knockout mice. No adverse effects of the new Mtb BN strain on the gut microbiota of BALB/c mice were revealed. The virulent strain Mtb H37Rv and the vaccine strain BCG decreased the main indicators of normocenosis (Bifidobacterium spp., Bifidobacterium animalis subsp. lactis, Akkermansia, and Erysipelotrichaceae) and led to disappearance of Clostridium perfingens, E. coli, Pseudomonas spp., which contributed to reduction of species diversity and the development of dysbiosis.
Topics: Female; Animals; Mice; Mycobacterium tuberculosis; BCG Vaccine; Escherichia coli; Tuberculosis; Mice, Inbred BALB C; Mycobacterium bovis
PubMed: 36723741
DOI: 10.1007/s10517-023-05705-5