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Frontiers in Immunology 2021Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens autophagic machinery. Nontuberculous mycobacteria... (Review)
Review
Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host-pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.
Topics: Animals; Anti-Bacterial Agents; Autophagy; Biological Evolution; Drug Resistance, Bacterial; Host-Pathogen Interactions; Humans; Immunity, Innate; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 34552591
DOI: 10.3389/fimmu.2021.728742 -
Scientific Reports Aug 2019A 59-year-old tobacco smoker male with chronic bronchitis living in Taravao, French Polynesia, Pacific, presented with a two-year growing nodule in the middle lobe of...
A 59-year-old tobacco smoker male with chronic bronchitis living in Taravao, French Polynesia, Pacific, presented with a two-year growing nodule in the middle lobe of the right lung. A guided bronchoalveolar lavage inoculated onto Löwenstein-Jensen medium yielded colonies of a rapidly-growing non-chromogenic mycobacterium designed as isolate P7213. The isolate could not be identified using routine matrix-assisted laser desorption ionization-time of flight-mass spectrometry and phenotypic and probe-hybridization techniques and yielded 100% and 97% sequence similarity with the respective 16S rRNA and rpoB gene sequences of Mycobacterium virginiense in the Mycobacterium terrae complex. Electron microscopy showed a 1.15 µm long and 0.38 µm large bacillus which was in vitro susceptible to rifampicin, rifabutin, ethambutol, isoniazid, doxycycline and kanamycin. Its 4,511,948-bp draft genome exhibited a 67.6% G + C content with 4,153 coding-protein genes and 87 predicted RNA genes. Genome sequence-derived DNA-DNA hybridization, OrthoANI and pangenome analysis confirmed isolate P7213 was representative of a new species in the M. terrae complex. We named this species "Mycobacterium mephinesia".
Topics: Bronchoalveolar Lavage; Genome, Bacterial; Humans; Lung; Male; Middle Aged; Mycobacterium; Nontuberculous Mycobacteria; Polynesia; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 31371776
DOI: 10.1038/s41598-019-47674-8 -
Drug Discovery Today Aug 2018Incidence of pulmonary diseases caused by non-tuberculous mycobacteria (NTM), relatives of Mycobacterium tuberculosis, is increasing at an alarming rate, surpassing... (Review)
Review
Incidence of pulmonary diseases caused by non-tuberculous mycobacteria (NTM), relatives of Mycobacterium tuberculosis, is increasing at an alarming rate, surpassing tuberculosis in many countries. Current chemotherapies require long treatment times and the clinical outcomes are often disappointing. There is an urgent medical need to discover and develop new, more-efficacious anti-NTM drugs. In this review, we summarize the current status of NTM drug development, and highlight knowledge gaps and scientific obstacles in NTM drug discovery. We propose strategies to reduce biological uncertainties and to begin to populate a NTM drug pipeline with attractive leads and drug candidates.
Topics: Animals; Anti-Bacterial Agents; Drug Discovery; Drug Resistance, Bacterial; Humans; Molecular Structure; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Structure-Activity Relationship
PubMed: 29635026
DOI: 10.1016/j.drudis.2018.04.001 -
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 -
Journal of Clinical Microbiology May 2019This minireview provides an update on recent taxonomic changes for the genus with an emphasis on newly identified species isolated from humans or associated with human... (Review)
Review
This minireview provides an update on recent taxonomic changes for the genus with an emphasis on newly identified species isolated from humans or associated with human disease.
Topics: Humans; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Phylogeny
PubMed: 30602442
DOI: 10.1128/JCM.01408-18 -
Clinics in Chest Medicine Mar 2015Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM... (Review)
Review
Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM grow and persist in many buildings. They are not contaminants of drinking water, but members of the natural drinking water microbial population. Infection occurs because humans share the same habitats. Because the ecology, antibiotic susceptibility, and virulence of individual species differs, identifying NTM isolates to species is important. Treatment requires multiple antibiotics. NTM patients are innately sensitive to NTM infection, resulting in reinfection. Knowledge of the sources of NTM can reduce exposure to environmental NTM.
Topics: Environmental Exposure; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Soil Microbiology; Water Microbiology; Water Supply
PubMed: 25676517
DOI: 10.1016/j.ccm.2014.10.003 -
Frontiers in Immunology 2022complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental... (Review)
Review
complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence of infection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.
Topics: Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Macrophages; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Lung Diseases
PubMed: 36505429
DOI: 10.3389/fimmu.2022.931876 -
Clinics in Chest Medicine Mar 2015Rapidly growing mycobacteria (RGM) include a diverse group of species. We address the treatment of the most commonly isolated RGM-M abscessus complex, M fortuitum, and M... (Review)
Review
Rapidly growing mycobacteria (RGM) include a diverse group of species. We address the treatment of the most commonly isolated RGM-M abscessus complex, M fortuitum, and M chelonae. The M abscessus complex is composed of 3 closely related species: M abscessus senso stricto (hereafter M abscessus), M massiliense, and M bolletii. Most studies address treatment of M abscessus complex, which accounts for 80% of lung disease caused by RGM and is the second most common RGM to cause extrapulmonary disease (after M fortuitum). The M abscessus complex represent the most drug-resistant nontuberculous mycobacteria and are the most difficult to treat.
Topics: Anti-Bacterial Agents; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 25676520
DOI: 10.1016/j.ccm.2014.10.004 -
Meat Science Dec 2014Nontuberculous mycobacteria (NTM) are ubiquitous, potentially pathogenic organisms that have been isolated from a variety of environmental sources. NTM have been... (Review)
Review
Nontuberculous mycobacteria (NTM) are ubiquitous, potentially pathogenic organisms that have been isolated from a variety of environmental sources. NTM have been isolated from various kinds of food and many studies support the hypothesis that food, especially raw or partially cooked products, plays a role as a source of NTM for humans. Animals with disseminated infection have been diagnosed with NTM not only in the gastro-intestinal tract and intestinal lymph nodes, but also in tissues like muscle and parenchymatous organs. Infected animals may harbor NTM in their tissues even without clinical symptoms and especially minced meat with the possible addition of lymph nodes are considered as potential source of NTM. The purpose of this paper was to review articles concerning the detection of mycobacteria in the muscle tissue and lymph nodes of domestic animals, farmed and free-living game and to summarize methods and techniques for their detection.
Topics: Animals; Animals, Domestic; Animals, Wild; Lymph Nodes; Meat Products; Muscle, Skeletal; Mycobacterium avium; Nontuberculous Mycobacteria
PubMed: 25170820
DOI: 10.1016/j.meatsci.2014.08.001 -
Enfermedades Infecciosas Y... Nov 2018Nontuberculous mycobacteria are a heterogeneous group of microorganisms that can often cause human infection, although they may also be considered to be contaminants or... (Review)
Review
Nontuberculous mycobacteria are a heterogeneous group of microorganisms that can often cause human infection, although they may also be considered to be contaminants or colonisers on occasions. The management of these infections must necessarily take into account the identification of isolated species and their in vitro susceptibility testing (although not for all of them), as well as the characteristics of the patient, because these treatments are usually prolonged and must be carried out by experts in the management of these infections. Classically divided into slowly growing mycobacteria and rapidly growing mycobacteria, the treatment regimens and the antibiotics used are different for both groups. In addition, in certain circumstances, this treatment must necessarily be linked to other measures (removal of foreign bodies, surgery) in order to maximise the likelihood of curing the patient.
Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Bacteriological Techniques; Biofilms; Disease Management; Drug Therapy, Combination; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium avium-intracellulare Infection; Nontuberculous Mycobacteria
PubMed: 29217094
DOI: 10.1016/j.eimc.2017.10.008