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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 -
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 -
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 -
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 -
Emerging Infectious Diseases Mar 2021We analyzed 98 Mycobacterium tuberculosis complex isolates collected in 2 regions of Algeria in 2015-2018 from 93 cases of pulmonary tuberculosis. We identified 93/98...
We analyzed 98 Mycobacterium tuberculosis complex isolates collected in 2 regions of Algeria in 2015-2018 from 93 cases of pulmonary tuberculosis. We identified 93/98 isolates as M. tuberculosis lineage 4 and 1 isolate as M. tuberculosis lineage 2 (Beijing). We confirmed 4 isolates as M. bovis by whole-genome sequencing.
Topics: Algeria; Beijing; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 33622469
DOI: 10.3201/eid2703.191823 -
The Journal of Dermatology Nov 2022Nontuberculous mycobacteria cause a wide range of infections, including cutaneous infections, in both immunocompromised and immunocompetent patients. Although pulmonary... (Review)
Review
Nontuberculous mycobacteria cause a wide range of infections, including cutaneous infections, in both immunocompromised and immunocompetent patients. Although pulmonary nontuberculous mycobacterial infections have increased significantly in Japan in recent years, there is less evidence on clinical and microbiological characteristics of cutaneous nontuberculous mycobacterial infections in Japan. We reviewed 86 Japanese cases reported between July 2016 and November 2021 and analyzed them in conjunction with the eight patients from our institution who were diagnosed with cutaneous nontuberculous mycobacterial infections by culture between 2015 and 2021. In the aggregate series, the average patient age was 60 years, and the ratio of immunocompromised hosts was 53%, both of which were higher than those in previous reports from other countries. No female predominance was observed, unlike in pulmonary nontuberculous mycobacteria infections. Rapidly growing mycobacteria accounted for 58% of the cases (n = 54), whereas slowly growing mycobacteria for 43% (n = 40). Mycobacterium marinum (also known as Mycobacteroides marinum) (n = 20, 21%) was the most common cause, followed by Mycobacterium chelonae (n = 18, 19%), Mycobacterium abscessus (also known as Mycobacteroides abscessus) (n = 15, 16%), and Mycobacterium ulcerans (n = 11, 12%). While clinical appearance was variable, M ulcerans infections usually presented with ulcers, while nodules were common among infections caused by M chelonae and M marinum. Disseminated infections involving multiple organs were observed in 23 patients (24%). Thirty-two cases (30%) were preceded by exposure, including raising or handling fish, trauma, and invasive medical procedures. Most patients were treated with more than two antibiotics and responded to therapy.
Topics: Animals; Japan; Skin Diseases, Bacterial; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Mycobacterium abscessus
PubMed: 35906770
DOI: 10.1111/1346-8138.16531 -
Emerging Infectious Diseases Mar 2022Although human infections caused by Mycobacterium mageritense are rare, there are some case reports involving sinusitis, pneumonia, and hospital-acquired infections in...
Although human infections caused by Mycobacterium mageritense are rare, there are some case reports involving sinusitis, pneumonia, and hospital-acquired infections in adults. We report a case of lymphadenitis caused by M. mageritense in a child in Spain.
Topics: Adult; Child; Family; Humans; Lymphadenitis; Mycobacteriaceae; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Pneumonia
PubMed: 35202540
DOI: 10.3201/eid2803.211486 -
Veterinary Medicine and Science Nov 2023Mycobacterium phlei is a gram-positive acid-fast mycobacterium from the family Mycobacteriaceae. It is a valuable resource for both natural drugs and microecological... (Review)
Review
Mycobacterium phlei is a gram-positive acid-fast mycobacterium from the family Mycobacteriaceae. It is a valuable resource for both natural drugs and microecological preparations. It has been widely used in the field of human medicine; however, in the field of animal husbandry and veterinary medicine, the research and application of M. phlei is still in the preliminary exploration stage. This study aims to summarize the research progress of M. phlei in the field of veterinary medicine and provide a valuable reference for future research. Key words, such as 'M. phlei', 'veterinary field', 'immune balancer', 'genome' and other relevant words to this study, were used to search through PubMed, Web of Science, SciELO, Science Direct and Google Scholar databases. The results showed that the culture conditions of M. phlei were relatively simple, but its bacterial composition and genome sequence were relatively complex, and various components in the cell wall may have immunoregulatory effects. Therefore, the inactivated preparation made from M. phlei can have various applications in the veterinary field, such as growth regulation, immune regulation, antitumour, anti-parasite and asthma treatment. The literature review indicates that M. phlei preparation is an efficient and convenient immune system balance agent. Despite the challenges associated with the use of M. phlei preparations, it has a strong potential for application in veterinary medicine.
Topics: Humans; Animals; Mycobacterium phlei; Mycobacterium; Asthma; Cell Wall
PubMed: 37723902
DOI: 10.1002/vms3.1262