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Biofouling Apr 2021The role of biofilms in pathogenicity and treatment strategies is often neglected in mycobacterial infections. In recent years, the emergence of nontuberculous... (Review)
Review
The role of biofilms in pathogenicity and treatment strategies is often neglected in mycobacterial infections. In recent years, the emergence of nontuberculous mycobacterial infections has necessitated the development of novel prophylactic strategies and elucidation of the mechanisms underlying the establishment of chronic infections. More importantly, the question arises whether members of the complex can form biofilms and contribute to latent tuberculosis and drug resistance because of the long-lasting and recalcitrant nature of its infections. This review discusses some of the molecular mechanisms by which biofilms could play a role in infection or pathological events in humans.
Topics: Biofilms; Humans; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 34024206
DOI: 10.1080/08927014.2021.1925886 -
Human Vaccines & Immunotherapeutics Aug 2021Despite aggressive eradication efforts, Tuberculosis (TB) remains a global health burden, one that disproportionally affects poorer, less developed nations. The only... (Review)
Review
Despite aggressive eradication efforts, Tuberculosis (TB) remains a global health burden, one that disproportionally affects poorer, less developed nations. The only vaccine approved for TB, the Bacillus of Calmette and Guérin (BCG) vaccine remains controversial because it's stated efficacy has been cited as anywhere from 0 to 80%. Nevertheless, there have been exciting discoveries about the mechanism of action of the BCG vaccine that suggests it has a role in immunization schedules today. We review recent data suggesting the vaccine imparts protection against both tuberculosis and non-tuberculosis pathogens via a newly discovered immune system called trained immunity. BCG's efficacy also appears to be tied to its affect on granulocytes at the epigenetic and hematopoietic stem cell levels, which we discuss in this article at length. We also write about how the different strains of the BCG vaccine elicit different immune responses, suggesting that certain BCG strains are more immunogenic than others. Finally, our review delves into how the current vaccine is being reformulated to be more efficacious, and track the development of the next generation vaccines against TB.
Topics: BCG Vaccine; Humans; Immunization Schedule; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines
PubMed: 33769193
DOI: 10.1080/21645515.2021.1885280 -
Trends in Immunology Apr 2022Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium bovis strain used as a vaccine to prevent Mycobacterium tuberculosis (M. tb) infection. Its ability to... (Review)
Review
Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium bovis strain used as a vaccine to prevent Mycobacterium tuberculosis (M. tb) infection. Its ability to potentiate the immune response induced by other vaccines and to promote nonspecific immunomodulatory effects has been described. These effects can be triggered by epigenetic reprogramming and metabolic shifts on innate immune cells, a phenomenon known as trained immunity. The induction of trained immunity may contribute to explain why BCG vaccination effectively decreases disease symptoms caused by pathogens different from M. tb. This article explains the importance of BCG immunization and the possible mechanisms associated with the induction of trained immunity, which might be used as a strategy for rapid activation of the immune system against unrelated pathogens.
Topics: BCG Vaccine; Humans; Immunity; Mycobacterium bovis; Mycobacterium tuberculosis; Vaccination
PubMed: 35074254
DOI: 10.1016/j.it.2021.12.006 -
Journal of the Formosan Medical... Jun 2020Great progress has recently been made in methodologies for identifying nontuberculous mycobacteria (NTM). Recommendations for drug susceptibility testing (DST) of NTM... (Review)
Review
Great progress has recently been made in methodologies for identifying nontuberculous mycobacteria (NTM). Recommendations for drug susceptibility testing (DST) of NTM have been expanded and updated by the Clinical and Laboratory Standards Institute and are crucial in the management of NTM infections. This article summarizes the clinically relevant molecular methods used to discriminate NTM species and updates the information on DST. Furthermore, recent progress on new antimicrobials against NTM infections is reviewed.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 32423573
DOI: 10.1016/j.jfma.2020.05.002 -
Seminars in Immunopathology Jun 2020Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing... (Review)
Review
Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.
Topics: Buruli Ulcer; Humans; Mycobacterium; Mycobacterium ulcerans; Skin
PubMed: 32100087
DOI: 10.1007/s00281-020-00790-4 -
International Journal of Molecular... Sep 2022The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that... (Review)
Review
The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that urgently demands the development of new potent anti-mycobacterial drugs. One of the approaches toward the identification of new drugs is fragment-based drug discovery (FBDD), which is the most ingenious among other drug discovery models, such as structure-based drug design (SBDD) and high-throughput screening. Specialized techniques, such as X-ray crystallography, nuclear magnetic resonance spectroscopy, and many others, are part of the drug discovery approach to combat the Mtb and NTM global menaces. Moreover, the primary drawbacks of traditional methods, such as the limited measurement of biomolecular toxicity and uncertain bioavailability evaluation, are successfully overcome by the FBDD approach. The current review focuses on the recognition of fragment-based drug discovery as a popular approach using virtual, computational, and biophysical methods to identify potent fragment molecules. FBDD focuses on designing optimal inhibitors against potential therapeutic targets of NTM and Mtb (PurC, ArgB, MmpL3, and TrmD). Additionally, we have elaborated on the challenges associated with the FBDD approach in the identification and development of novel compounds. Insights into the applications and overcoming the challenges of FBDD approaches will aid in the identification of potential therapeutic compounds to treat drug-sensitive and drug-resistant NTMs and Mtb infections.
Topics: Crystallography, X-Ray; Drug Design; Drug Discovery; Humans; Mycobacterium Infections; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 36142582
DOI: 10.3390/ijms231810669 -
EBioMedicine Oct 2021
Topics: Host-Pathogen Interactions; Humans; Mycobacterium avium; Mycobacterium tuberculosis; Tuberculosis
PubMed: 34717837
DOI: 10.1016/j.ebiom.2021.103659 -
Frontiers in Cellular and Infection... 2023
Topics: Mycobacterium tuberculosis
PubMed: 37168392
DOI: 10.3389/fcimb.2023.1201012 -
Sub-cellular Biochemistry 2022The mycobacteria genus is responsible for numerous infectious diseases that have afflicted the human race since antiquity-tuberculosis and leprosy in particular. An...
The mycobacteria genus is responsible for numerous infectious diseases that have afflicted the human race since antiquity-tuberculosis and leprosy in particular. An important contributor to their evolutionary success is their unique cell envelope, which constitutes a quasi-impermeable barrier, protecting the microorganism from external threats, antibiotics included. The arabinofuranosyltransferases are a family of enzymes, unique to the Actinobacteria family that mycobacteria genus belongs to, that are critical to building of this cell envelope. In this chapter, we will analyze available structures of members of the mycobacterial arabinofuranosyltransferase, clarify their function, as well as explore the common themes present amongst this family of enzymes, as revealed by recent research.
Topics: Anti-Bacterial Agents; Cell Membrane; Cell Wall; Humans; Mycobacterium; Mycobacterium tuberculosis
PubMed: 36151383
DOI: 10.1007/978-3-031-00793-4_12 -
Frontiers in Cellular and Infection... 2023We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) and .
OBJECTIVES
We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) and .
METHODS
The minimum inhibitory concentrations (MICs) of 11 antibiotics, against slow-growing mycobacteria (SGMs) and rapid-growing mycobacteria (RGMs) were tested using the microplate alamarBlue assay. The activities of bedaquiline, clofazimine, moxifloxacin, rifabutin, PBTZ169 and pretomanid against four common NTMs were assessed in murine models.
RESULTS
PBTZ169 and pretomanid had MICs of >32 μg/mL against most NTM reference and clinical strains. However, PBTZ169 was bactericidal against (3.33 and 1.49 log10 CFU reductions in the lungs and spleen, respectively) and (2.29 and 2.24 CFU reductions in the lungs and spleen, respectively) in mice, and bacteriostatic against Mycobacterium avium and . Pretomanid dramatically decreased the CFU counts of (3.12 and 2.30 log10 CFU reductions in the lungs and spleen, respectively), whereas it showed moderate inhibition of and . Bedaquiline, clofazimine, and moxifloxacin showed good activities against four NTMs and . Rifabutin did not inhibit and in mice.
CONCLUSION
PBTZ169 appears to be a candidate for treating four common NTM infections. Pretomanid was more active against , and than against .
Topics: Animals; Mice; Mycobacterium abscessus; Mycobacterium avium; Mycobacterium fortuitum; Mycobacterium chelonae; Clofazimine; Moxifloxacin; Mice, Inbred BALB C; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Mycobacterium Infections; Rifabutin; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests
PubMed: 37077530
DOI: 10.3389/fcimb.2023.1115530