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Epidemiology and Infection Dec 2022A cross-sectional and retrospective study of patients with spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in...
A cross-sectional and retrospective study of patients with spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in isolations of nontuberculous mycobacteria (NTM). The number of patients with positive samples for spp. grew from 56 in 2009 to 83 in 2019. The proportion of NTM rose from 39.3% to 49.4% ( = 0.240), with being more frequent in 2009 and in 2019, and decreased from 60.7% to 50.6%. Higher age was associated with NTM in both years, and pulmonary disease and immunosuppression were associated with NTM in 2019 ( < 0.05), with weak to moderate correlation ( = 0.231-0.343). The overall rise of NTM, allied to their known capacity to resist antimicrobial therapy, alerts clinicians to the importance of recognising potential risk factors for infection and improving future prevention strategies.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Cross-Sectional Studies; Mycobacterium avium Complex; Mycobacterium
PubMed: 36503567
DOI: 10.1017/S0950268822000899 -
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 -
American Journal of Respiratory Cell... Aug 2020The incidence and prevalence of nontuberculous mycobacteria (NTM) lung disease is rising worldwide and accounts for most clinical cases of NTM disease. NTM infections... (Review)
Review
The incidence and prevalence of nontuberculous mycobacteria (NTM) lung disease is rising worldwide and accounts for most clinical cases of NTM disease. NTM infections occur in both immunocompetent and immunocompromised hosts. Macrophages are the primary host cells that initiate an immune response to NTM. Defining the molecular events that govern the control of infection within macrophages is fundamental to understanding the pathogenesis of NTM disease. Here, we review key macrophage host signaling pathways that contribute to the host immune response to pulmonary NTM infections. In this review, we focus primarily on NTM that are known to cause lung disease, including , , and .
Topics: Animals; Humans; Lung Diseases; Macrophages; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Signal Transduction
PubMed: 32160017
DOI: 10.1165/rcmb.2019-0241TR -
Canadian Respiratory Journal 2017Nontuberculous Mycobacteria (NTM) are causing growing health problems worldwide. This is indicated by an increasing amount of scientific reports showing not only... (Review)
Review
Nontuberculous Mycobacteria (NTM) are causing growing health problems worldwide. This is indicated by an increasing amount of scientific reports showing not only well-identified species reemerging but also emergence of new species. The emergence and reemergence of NTM are particularly worrying in developing countries due to scarce published data and improper identification. Here we aimed to examine the main epidemiological aspects and diagnostic challenges associated with NTM in countries of the Gulf Cooperation Council (GCC) and compare these findings to the international arena findings. Data revealed that countries of the GCC are largely dominated by rapidly growing mycobacteria species such as (29%) and (17%) with high rate of definitive respiratory diseases. On the other hand, most of the developed countries are dominated by slowly growing mycobacteria such as MAC, , and . More efforts are needed, however, to gain insights into NTM issues in countries of the GCC.
Topics: Environmental Microbiology; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Pneumonia, Bacterial; Saudi Arabia
PubMed: 28348502
DOI: 10.1155/2017/5035932 -
International Journal of Molecular... Aug 2020Outside of and , nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections... (Review)
Review
Outside of and , nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biological Transport; Drug Discovery; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Humans; Iodophors; Isoxazoles; Membrane Transport Proteins; Mycobacterium Infections, Nontuberculous; Mycolic Acids; Nontuberculous Mycobacteria; Polysaccharides; Spiro Compounds
PubMed: 32867307
DOI: 10.3390/ijms21176202 -
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 -
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 -
Annals of Clinical Microbiology and... Feb 2023Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important... (Review)
Review
Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important role in controlling NTM infection and contribute to protective immune responses within the early phase of infection. However, these cells are also adversely associated with disease progression and exacerbation and can contribute to pathology, for example in the development of bronchiectasis. In this review, we discuss the key findings and latest evidence regarding the diverse functions of neutrophils in NTM infection. First, we focus on studies that implicate neutrophils in the early response to NTM infection and the evidence reporting neutrophils' capability to kill NTM. Next, we present an overview of the positive and negative effects that characterise the bidirectional relationship between neutrophils and adaptive immunity. We consider the pathological role of neutrophils in driving the clinical phenotype of NTM-PD including bronchiectasis. Finally, we highlight the current promising treatments in development targeting neutrophils in airways diseases. Clearly, more insights on the roles of neutrophils in NTM-PD are needed in order to inform both preventative strategies and host-directed therapy for these important infections.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Neutrophils; Lung Diseases; Bronchiectasis
PubMed: 36800956
DOI: 10.1186/s12941-023-00562-6