Recent Advances in Nontuberculous Mycobacteria (NTM)

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 16 August 2024 | Viewed by 9255

Special Issue Editors


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Guest Editor
National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
Interests: clinical microbiology; genotyping of Mycobacterium tuberculosis complex strains; TB transmission; Mycobacterium drug resistance

E-Mail Website
Guest Editor
National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
Interests: clinical microbiology; microbiological diagnostics of tuberculosis and mycobacteriosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nontuberculous mycobacteria (NTM) constitute a group of over 180 Mycobacterium species, with the exception of the Mycobacterium tuberculosis complex and Mycobacterium leprae. NTM species can cause a variety of infections in humans and animals, including pneumonia, lung abscess, pleural infection, meningitis, lymphadenitis, and skin and soft tissue infection. Mycobacterioses are difficult to treat because therapy is long, expensive, more toxic, and more prone to failure than tuberculosis treatment. Recently, an increase in the number of infections caused by NTM bacilli has been recorded all over the world.

All NTM species are acid-fast; therefore, the staining of microscopic smears using fluorescence and the Ziehl–Neelsen methods is not sufficient for species identification, or for distinguishing NTM from MTBC species. The proper diagnosis of mycobacteriosis is based on clinical features and microbiological tests, including culture, histopathology and molecular methods. Knowing the capabilities and limitations of laboratory testing is critical to making the right clinical decisions. Hence, one of the most important roles of modern microbiology laboratories is the diagnosis and species identification of NTM, and distinguishing them from MTBC strains.

In this Special Issue, we will provide an overview of the current diagnostic options for suspected NTM infection.

Dr. Monika Kozińska
Prof. Dr. Ewa Augustynowicz-Kopec
Guest Editors

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Keywords

  • Mycobacteriosis
  • identification
  • nontuberculous mycobacteria (NTM)
  • mycobacteria other than tuberculosis (MOTT)
  • epidemiology
  • Mycobacterium spp.
  • microbiological diagnostics

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Published Papers (7 papers)

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18 pages, 2859 KiB  
Article
Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of Mycobacterium peregrinum Infections
by Ji Won Lee, Ho Won Kim, A-Reum Yu, Hoe Sun Yoon, Minji Kang, Hwan-Woo Park, Sung Ki Lee, Jake Whang and Jong-Seok Kim
Pathogens 2023, 12(12), 1446; https://doi.org/10.3390/pathogens12121446 - 13 Dec 2023
Cited by 1 | Viewed by 1049
Abstract
Mycobacterium peregrinum (Mpgm) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. Mpgm is considered an opportunistic pathogen that causes infection in immunocompromised individuals [...] Read more.
Mycobacterium peregrinum (Mpgm) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. Mpgm is considered an opportunistic pathogen that causes infection in immunocompromised individuals or those with underlying medical conditions. Although there have been clinical reports on Mpgm, reports of the immune response and metabolic reprogramming have not been published. Thus, we studied standard Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) using macrophages and mouse bone marrow-derived cells. Mpgm has two types of colony morphologies: smooth and rough. We grew all strains on the 7H10 agar medium to visually validate the morphology. Cytokine levels were measured via ELISA and real-time PCR. The changes in mitochondrial function and glycolysis in Mpgm-infected macrophages were measured using an extracellular flux analyzer. Mpgm-S-infected macrophages showed elevated levels of inflammatory cytokines, including interleukin (IL)-6, IL-12p40, and tumor necrosis factor (TNF)-α, compared to Mpgm-ATCC- and Mpgm-R-infected macrophages. Additionally, our findings revealed metabolic changes in Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) during infection; significant changes were observed in the mitochondrial respiration, extracellular acidification, and the oxygen consumption of BMDMs upon Mpgm-S infection. In summary, within the strains examined, Mpgm-S displayed greater virulence, triggered a heightened immune response, and induced more profound shifts in bioenergetic metabolism than Mpgm-ATCC and Mpgm-R. This study is the first to document distinct immune responses and metabolic reorganization following Mpgm infection. These findings lay a crucial foundation for further investigations into the pathogenesis of Mpgm. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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11 pages, 964 KiB  
Article
Molecular Characterisation of M. kansasii Isolates by Whole-Genome Sequencing
by Priya Rajendran, Chandrasekaran Padmapriyadarsini, Naveenkumar Nagarajan, Roja Samyuktha, Vadivu Govindaraju, Radhika Golla, Shanmugavel Ashokkumar and Sivakumar Shanmugam
Pathogens 2023, 12(10), 1249; https://doi.org/10.3390/pathogens12101249 - 17 Oct 2023
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Abstract
M. kansasii is the most common non-tuberculous mycobacteria, known to be causing pulmonary and extrapulmonary diseases in humans. Based on molecular methods, M. kansasii has been previously classified into seven different subtypes. Now, based on whole-genome sequence analysis, a new species designation was [...] Read more.
M. kansasii is the most common non-tuberculous mycobacteria, known to be causing pulmonary and extrapulmonary diseases in humans. Based on molecular methods, M. kansasii has been previously classified into seven different subtypes. Now, based on whole-genome sequence analysis, a new species designation was proposed, in which M. kansasii species was designated subtype 1 and is of pathogenic significance in both immunocompetent and immunocompromised patients. The aim of the study is to examine the distribution of subtypes, based on whole-genome sequence analysis, and identify the genetic determinants of drug resistance for the isolates. Whole-genome sequencing was performed using 12 isolates for which phenotypic DST results were available. A phylogenetic tree was constructed by alignment of each of the 12 isolates and the additional strains, as well as the M. kansasii reference strain, using the MAFFT algorithm. Based on this analysis, all 12 isolates were classified as subtype I. Drug-resistant mutations were identified by analysing the isolates with known drug-resistant loci of MTB and NTM. Although we had mutations in the drug-resistant genes, the significance of those mutations could not be explored due to the minimal availability of data available to compare. Further large-scale studies targeting the phenotypic and genotypic drug-resistance pattern, along with whole-genome analysis, will facilitate a better understanding of the resistance mechanisms involved in M. kansasii. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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10 pages, 439 KiB  
Article
Mycobacterial Interspersed Repeat Unit–Variable Number Tandem Repeat Typing of Mycobacterium avium Strains Isolated from the Lymph Nodes of Free-Living Carnivorous Animals in Poland
by Blanka Orłowska, Marta Majchrzak, Anna Didkowska, Krzysztof Anusz, Monika Krajewska-Wędzina, Anna Zabost, Sywia Brzezińska, Monika Kozińska, Ewa Augustynowicz-Kopeć, Kaja Urbańska, Mirosław Welz and Paweł Parniewski
Pathogens 2023, 12(9), 1184; https://doi.org/10.3390/pathogens12091184 - 21 Sep 2023
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Abstract
Non-tuberculous mycobacteria (NTM) are ubiquitous organisms, of which some, especially those of the Mycobacterium avium complex (MAC), may be opportunistic animal and human pathogens. Infection with NTM can interfere with tuberculosis (TB) diagnosis and induce zoonoses, especially in immunocompromised individuals. Diseases caused by [...] Read more.
Non-tuberculous mycobacteria (NTM) are ubiquitous organisms, of which some, especially those of the Mycobacterium avium complex (MAC), may be opportunistic animal and human pathogens. Infection with NTM can interfere with tuberculosis (TB) diagnosis and induce zoonoses, especially in immunocompromised individuals. Diseases caused by NTM have become more readily recognized; however, they are likely still underestimated. In this study, we identified and genotyped Mycobacterium avium strains that were isolated during TB monitoring among free-living carnivorous animals from southeastern Poland. In 2011–2020, lymph node samples from 192 such animals were tested for mycobacteria. A total of 41 isolates of M. avium strains were detected with the use of IS901, IS900, IS1245, and mycobacterial interspersed repeat unit–variable number tandem repeat (MIRU-VNTR) identification. Thirty-three were identified as M. avium subsp. avium. These strains were derived from 1 beech marten (Martes foina), 1 common buzzard (Buteo buteo), 2 European badgers (Meles meles), 3 wolves (Canis lupus), and 26 red foxes (Vulpes vulpes). One strain isolated from a wolf was identified as M. avium subsp. hominissuis. The results show the widespread occurrence of MAC bacilli in the studied environment and additionally comprise new data on the molecular characteristics of M. avium subspecies carried by free-living southeastern Polish carnivores. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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12 pages, 1621 KiB  
Article
Trends from the Last Decade with Nontuberculous Mycobacteria Lung Disease (NTM-LD): Clinicians’ Perspectives in Regional Center of Pulmonology in Bydgoszcz, Poland
by Grzegorz Przybylski, Jakub Bukowski, Weronika Kowalska, Marta Pilaczyńska-Cemel and Dorota Krawiecka
Pathogens 2023, 12(8), 988; https://doi.org/10.3390/pathogens12080988 - 28 Jul 2023
Cited by 3 | Viewed by 1248
Abstract
Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and [...] Read more.
Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and assess the frequency and clinical relevance of isolation of NTM in the Regional Center of Pulmonology in Bydgoszcz, hospital of Northern Poland. Design: Clinical, radiological, and microbiological data were collected from all patients from whom NTM was isolated between 2013 and 2022. Data were reviewed retrospectively. Diagnostic criteria for NTM-LD published by the American Thoracic Society (ATS) were used to determine clinical relevance. Material and methods: The study comprised 81,985 clinical specimens submitted for mycobacterial culture in the Department of Microbiology at the Regional Center of Pulmonology in Bydgoszcz between 2013 and 2022. Clinical specimens were processed according to the standard procedure in mycobacteria laboratories in Poland. NTM strains were identified using analysis of mycolic acids by chromatography as well as GenoType NTM-DR, GenoType Mycobacterium AS, and GenoType Mycobacterium CM. Results: There were 395 patients with NTM strains between 2013 and 2022. Out of them, 149 cases met the diagnostic criteria of NTM-LD and were classified as definite cases. M. kansasii (n = 77) was the most common species in the group (51.68%), followed by M. avium complex (n = 46). Patients with NTM-LD were 22–88 years old (median age was 60 years). There were 81 men and 68 women. The most common symptoms were cough, hemoptysis, and fever. Radiological X-ray images were dominated by infiltrative lesions in the upper and middle lobe of the right lung with cavities; the changes were in the upper lobe of the left lung and on both sides of the chest. They were smokers in 61%. The most common concomitant diseases were chronic obstructive pulmonary disease (COPD), diabetes mellitus, pulmonary carcinoma, and human immunodeficiency virus (HIV) infection, and other immunodeficiencies. The most common treatment was isoniazid, ethambutol, rifampicin, and ofloxacin for 18 months with a minimum of 12 months of culture negativity. Conclusions: NTM-LD infections are present with other pulmonary illnesses and extrapulmonary diseases and may be connected to primary immunologic deficiencies. These diseases concern patients of all ages and have various clinical manifestations. M. kansasii and MAC are the most prevalent NTM isolates among respiratory samples in Northern Poland. In addition, an increase in MAC and a decrease in M. kansasii both in cultivation and the cause of NTM-LD were reported. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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13 pages, 1311 KiB  
Article
A Comparison of Clinical and Radiographic Signs of Nontuberculous Mycobacterial Pulmonary Disease, Destructive Drug-Resistant Pulmonary Tuberculosis and a Combination of Nontuberculous Mycobacterium Pulmonary Disease and Pulmonary Tuberculosis
by Dmitrii Giller, Galina Scherbakova, Inga Enilenis, Ivan Martel, Oleg Kesaev, Vadim Koroev, Anna Popova, Alexandr Ilyukhin, Valeria Basangova, Sergey Smerdin, Shokirjon Mayusupov, Sergey Saenko, Olga Frolova, Veronika Vinarskaya and Lyudmila Severova
Pathogens 2023, 12(7), 887; https://doi.org/10.3390/pathogens12070887 - 29 Jun 2023
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Abstract
A misdiagnosis of isolated pulmonary tuberculosis (pTB) is highly likely when a patient has nontuberculous mycobacterial pulmonary disease (NTMPD) or a combination of nontuberculous mycobacterium pulmonary disease and pulmonary tuberculosis. Frequently, bacterial excretion is absent or only Mycobacteria tuberculosis (MBT) is found. This [...] Read more.
A misdiagnosis of isolated pulmonary tuberculosis (pTB) is highly likely when a patient has nontuberculous mycobacterial pulmonary disease (NTMPD) or a combination of nontuberculous mycobacterium pulmonary disease and pulmonary tuberculosis. Frequently, bacterial excretion is absent or only Mycobacteria tuberculosis (MBT) is found. This often results in an incorrect diagnosis and subsequent misinformed treatment regimes. In order to determine possible clinical and radiographic differences between patients with NTMPD (Group 1), destructive drug-resistant pulmonary tuberculosis (Group 3) and a combination of NTMPD and pTB (Group 2) we compare clinical and radiographic signs for these three patient groups. When comparing with Group 3 (2.5%), Groups 1 (25%) and 2 (17.4%) have a substantially higher incidence of pulmonary haemorrhages. Thus, upon clinically observing the combination of pTB and NTMPD, there are no pathognomonic clinical and radiographic detected symptoms. However, the presence of an indolent course, hemoptysis and bronchiectasis in the presence of acid-fast bacteria (or identified MBT) in the sputum makes it possible to suspect not simple pTB, but a combination of pTB and NTMPD. To clarify this necessitated in-depth bacteriological examination. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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12 pages, 907 KiB  
Systematic Review
A Systematic Review of Factors Associated with Mortality among Patients with Mycobacterium avium Complex Lung Disease
by Nobuhiro Fujishima, Kosaku Komiya, Mari Yamasue, Kazufumi Hiramatsu and Jun-ichi Kadota
Pathogens 2023, 12(11), 1331; https://doi.org/10.3390/pathogens12111331 - 08 Nov 2023
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Abstract
Purpose: As the number of patients with Mycobacterium avium complex lung disease is significantly increasing worldwide, several studies have focused on the prognostic factors associated with the disease. This systematic review investigated the factors associated with mortality among patients with Mycobacterium avium complex [...] Read more.
Purpose: As the number of patients with Mycobacterium avium complex lung disease is significantly increasing worldwide, several studies have focused on the prognostic factors associated with the disease. This systematic review investigated the factors associated with mortality among patients with Mycobacterium avium complex lung disease. Methods: Two investigators independently identified studies that were designed to determine risk factors for mortality in patients with Mycobacterium avium complex lung disease from PubMed, the Cochrane Register of Control Trial database, and EMBASE (accessed on 25 November 2022). Results: Of the 1133 titles and abstracts screened, 54 full texts were selected for review, and 15 studies were finally included in this systematic review. The most commonly studied risk factors were advanced age and low body mass index (11 studies for each), followed by male sex (8 studies), hypoalbuminemia (5 studies), and cavity (5 studies). In each study, these factors were mostly associated with increased all-cause mortality among patients with Mycobacterium avium complex lung disease as confirmed via multivariate analysis. Conclusions: Advanced age, male sex, low body mass index, hypoalbuminemia, and cavity are likely to be the common risk factors for all-cause mortality among patients with Mycobacterium avium complex lung disease, suggesting that patients with these factors need to be carefully monitored. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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9 pages, 263 KiB  
Case Report
First Case Reports of Nontuberculous Mycobacterial (NTM) Lung Disease in Ecuador: Important Lessons to Learn
by Gustavo Echeverria, Veronica Rueda, Wilson Espinoza, Carlos Rosero, Martín J. Zumárraga and Jacobus H. de Waard
Pathogens 2023, 12(4), 507; https://doi.org/10.3390/pathogens12040507 - 23 Mar 2023
Cited by 3 | Viewed by 2102
Abstract
Nontuberculous mycobacteria (NTM) lung infections are often misdiagnosed as tuberculosis, which can lead to ineffective antibiotic treatments. In this report, we present three cases of NTM lung infections in Ecuador that were initially diagnosed and treated as tuberculosis based on the results of [...] Read more.
Nontuberculous mycobacteria (NTM) lung infections are often misdiagnosed as tuberculosis, which can lead to ineffective antibiotic treatments. In this report, we present three cases of NTM lung infections in Ecuador that were initially diagnosed and treated as tuberculosis based on the results of sputum smear microscopy. The patients, all male, included two immunocompetent individuals and one HIV-positive subject. Unfortunately, sputum culture was not initiated until late in the course of the disease and the cause of the lung infection, Mycobacterium avium complex (MAC), was only identified after the patients had either passed away or were lost to follow-up. These cases are the first documented cases of NTM lung infections in the English medical literature from Ecuador. We emphasize the importance of accurate diagnosis of NTM infections by culture and identification to species level. Sputum smear staining alone cannot differentiate between mycobacterial species, which can lead to misidentification and ineffective treatments. Additionally, reporting NTM pulmonary disease as a notifiable disease to national TB control programs is recommended to obtain accurate prevalence data. These data are critical in determining the importance of this public health problem and the necessary actions needed to address it. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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