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Frontiers in Immunology 2022Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence... (Review)
Review
Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence worldwide. Knowledge of NTM's mechanisms of virulence is lacking, as molecular research of these bacteria is challenging, sometimes more than that of M. tuberculosis (Mtb), and far less resources are allocated to their investigation. While some of the virulence mechanisms are common to several mycobacteria including Mtb, others NTM species-specific. Among NTMs, Mycobacterium abscessus (Mabs) causes some of the most severe and difficult to treat infections, especially chronic pulmonary infections. Mabs survives and proliferates intracellularly by circumventing host defenses, using multiple mechanisms, many of which remain poorly characterized. Some of these immune-evasion mechanisms are also found in Mtb, including phagosome pore formation, inhibition of phagosome maturation, cytokine response interference and apoptosis delay. While much is known of the role of Mtb-secreted effector molecules in mediating the manipulation of the host response, far less is known of the secreted effector molecules in Mabs. In this review, we briefly summarize the knowledge of secreted effectors in Mtb (such as ESX secretion, SecA2, TAT and others), and draw the parallel pathways in Mabs. We also describe pathways that are unique to Mabs, differentiating it from Mtb. This review will assist researchers interested in virulence-associated secretion in Mabs by providing the knowledge base and framework for their studies.
Topics: Mycobacterium abscessus; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Phagosomes; Virulence
PubMed: 35880173
DOI: 10.3389/fimmu.2022.938895 -
Immunological Reviews May 2021Upon infection, mycobacteria, such as Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a... (Review)
Review
Upon infection, mycobacteria, such as Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a series of intracellular processes that promote mycobacterial killing. Mycobacteria, however, have developed multiple counter-strategies to persist and survive inside host cells. By manipulating host effector mechanisms, including phagosome maturation, vacuolar escape, autophagy, antigen presentation, and metabolic pathways, pathogenic mycobacteria are able to establish long-lasting infection. Counteracting these mycobacteria-induced host modifying mechanisms can be accomplished by host-directed therapeutic (HDT) strategies. HDTs offer several major advantages compared to conventional antibiotics: (a) HDTs can be effective against both drug-resistant and drug-susceptible bacteria, as well as potentially dormant mycobacteria; (b) HDTs are less likely to induce bacterial drug resistance; and (c) HDTs could synergize with, or shorten antibiotic treatment by targeting different pathways. In this review, we will explore host-pathogen interactions that have been identified for Mtb for which potential HDTs impacting both innate and adaptive immunity are available, and outline those worthy of future research. We will also discuss possibilities to target NTM infection by HDT, although current knowledge regarding host-pathogen interactions for NTM is limited compared to Mtb. Finally, we speculate that combinatorial HDT strategies can potentially synergize to achieve optimal mycobacterial host immune control.
Topics: Anti-Bacterial Agents; Autophagy; Host-Pathogen Interactions; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 33565103
DOI: 10.1111/imr.12951 -
Respiratory Investigation Mar 2023In recent years, the incidence and prevalence of pulmonary nontuberculous mycobacterial (NTM) disease have increased worldwide. Although the reasons for this increase... (Review)
Review
In recent years, the incidence and prevalence of pulmonary nontuberculous mycobacterial (NTM) disease have increased worldwide. Although the reasons for this increase are unclear, dealing with this disease is essential. Pulmonary NTM disease is a chronic pulmonary infection caused by NTM bacteria, which are ubiquitous in various environments. In Japan, Mycobacterium avium-intracellulare complex (MAC) accounts for approximately 90% of the causative organisms of pulmonary NTM disease, which is also called pulmonary MAC disease or pulmonary MAI disease. It is important to elucidate the pathophysiology of this disease, which occurs frequently in postmenopausal women despite the absence of obvious immunodeficiency. The pathophysiology of this disease has not been fully elucidated; however, it can largely be divided into bacterial (environmental) and host-side problems. The host factors can be further divided into immune and airway problems. The authors suggest that the triangular relationship between bacteria, immunity, and the airway is important in the pathophysiology of this disease. The latest findings on the pathophysiology of pulmonary NTM disease are reviewed.
Topics: Humans; Female; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Nontuberculous Mycobacteria; Lung Diseases; Lung
PubMed: 36640546
DOI: 10.1016/j.resinv.2022.12.002 -
Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
Current Opinion in Organ Transplantation Aug 2019Nontuberculous mycobacteria (NTM) are emerging pathogens of concern especially in solid organ transplant candidates and recipients. This review aims to address... (Review)
Review
PURPOSE OF REVIEW
Nontuberculous mycobacteria (NTM) are emerging pathogens of concern especially in solid organ transplant candidates and recipients. This review aims to address diagnostic challenges, new and emerging treatment options, and infection prevention.
RECENT FINDINGS
The incidence of NTM infections in transplant candidates and recipients is rising. The infection prevalence of these environmental pathogens varies geographically by species with a coastal predominance. Although existing guidelines from the American Thoracic Society, Infectious Diseases Society of America, and British Thoracic Society provide recommendations for diagnosis and management, they do not fully address the subtle nuances and challenges faced in managing infections in immunocompromised transplant recipients. Evolving data on new therapeutic agents and their use in combination therapy will help individualize treatment regimens while limiting adverse effects and improving compliance. Use of combination β-lactams, avibactam, tedizolid, clofazimine, bedaquiline, liposomal amikacin, and ciprofloxacin for commonly isolated species such as Mycobacterium abscessus and Mycobacterium avium complex have proven effective.
SUMMARY
Further studies are needed to determine the incidence of NTM infection in a prospective, multicentric manner and evaluate the most promising synergistic treatment combinations in transplant recipients.
Topics: Humans; Nontuberculous Mycobacteria; Organ Transplantation; Prospective Studies
PubMed: 31145153
DOI: 10.1097/MOT.0000000000000665 -
Clinics in Chest Medicine Dec 2023Nontuberculous mycobacteria (NTM) pulmonary disease is a chronic progressive pulmonary infectious disease caused by low virulence pathogens. The existence of host... (Review)
Review
Nontuberculous mycobacteria (NTM) pulmonary disease is a chronic progressive pulmonary infectious disease caused by low virulence pathogens. The existence of host susceptibility to NTM infection has been recognized from a high incidence among Asians compared to other populations in the United States, a high incidence among slender, middle-aged women, and the presence of familial clusters. Recent whole exome sequencing and genome-wide association studies have identified immune, CFTR, cilia, connective tissue and ion homeostasis genes as host susceptibility genes. Large-scale international collaborative studies and functional analyses are expected to elucidate host susceptibility in the future.
Topics: Middle Aged; Humans; Female; United States; Genome-Wide Association Study; Mycobacterium Infections, Nontuberculous; Lung Diseases; Lung; Nontuberculous Mycobacteria
PubMed: 37890911
DOI: 10.1016/j.ccm.2023.07.002 -
Current Opinion in Pulmonary Medicine Nov 2021Nontuberculous mycobacteria (NTM) are challenging infections among people with cystic fibrosis (pwCF) as the source, modes of transmission, and best practices for... (Review)
Review
PURPOSE OF REVIEW
Nontuberculous mycobacteria (NTM) are challenging infections among people with cystic fibrosis (pwCF) as the source, modes of transmission, and best practices for diagnosis and treatment are not known. Investigators have defined aspects of NTM infection that are unique to the CF population, as well as features shared with other conditions at risk. This review describes recent advances in our understanding of NTM infection among pwCF.
RECENT FINDINGS
The presence of dominant circulating clones of Mycobacterium abscessus within the CF community worldwide continue to be described, as well as pathogen phenotypes that could evoke greater environmental fitness and infectivity. The risk of direct or indirect transmission between pwCF remains an active focus of investigation, with divergent findings and conclusions reached in a site-specific fashion. Derived largely from studies in non-CF populations, new clinical guidelines are now available. A wide variety of agents are in preclinical development or early phase trials with promising findings, and new therapeutic targets have been identified as our understanding of the complex biology of NTM continues to expand.
SUMMARY
Significant challenges remain in the fight against NTM, however, recent advances in our understanding of the genetics, epidemiology and pathophysiology of pulmonary NTM infection in pwCF are leading efforts to improve clinical care.
Topics: Cystic Fibrosis; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Nontuberculous Mycobacteria; Phenotype
PubMed: 34431787
DOI: 10.1097/MCP.0000000000000816 -
F1000Research 2019Nontuberculous mycobacteria (NTM) are members of the Mycobacterium genus other than complex and . NTM are widely distributed in the environment and are increasingly... (Review)
Review
Nontuberculous mycobacteria (NTM) are members of the Mycobacterium genus other than complex and . NTM are widely distributed in the environment and are increasingly recognized as causes of chronic lung disease that can be challenging to treat. In this brief review, we consider recent developments in the ecology, epidemiology, natural history, and treatment of NTM lung disease with a focus on complex (MAC) and complex
Topics: Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex
PubMed: 31602293
DOI: 10.12688/f1000research.20096.1 -
Clinics in Chest Medicine Dec 2023Nontuberculous mycobacterial pulmonary disease caused by the less common nontuberculous mycobacteria have distinct features depending on the species. Diagnostic... (Review)
Review
Nontuberculous mycobacterial pulmonary disease caused by the less common nontuberculous mycobacteria have distinct features depending on the species. Diagnostic evaluation follows the established criteria for all nontuberculous mycobacteria, but with certain qualifications given species-specific and regional differences in pathogenicity. Clinicians should first institute nonpharmacologic management and evaluate clinical, radiologic, and microbiologic factors in the decision regarding antimycobacterial therapy. Treatment is challenging, and evidence-based recommendations are limited for most species. Drug susceptibility testing is used to help with regimen selection; however, this approach is imperfect given the uncertain correlation between in vitro activity and clinical response for most drugs.
Topics: Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Lung Diseases
PubMed: 37890917
DOI: 10.1016/j.ccm.2023.06.011 -
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