Non-Tuberculous Mycobacteria: Emerging Diseases and Health Impacts

Chronic pulmonary aspergillosis (CPA) has been reported to be associated with poor prognosis in non-tuberculous mycobacteria (NTM)-pulmonary disease (PD) patients. However, whether isolation of Apergillus species is associated with poor outcome or mostly just the reflection of colonization is a widely debated issue and a yet unsolved question. We conducted this single-centered retrospective cohort study of 409 NTM-PD patients to assess the impacts and prevalence of Aspergillus isolation and CPA development. The median observation time was 85 months. Aspergillus species were isolated from 79 (19.3%) and 23 (5.6%) developed CPA. Isolation of Aspergillus species was not associated with mortality in NTM-PD patients (p = 0.9016). Multivariate logistic regression analysis revealed that higher CRP (p = 0.0213) and AFB stain positivity (p = 0.0101) were independently associated with Aspergillus isolation. Different mycobacterial species were not associated with Aspergillus isolation. Survival curves for patients with CPA diagnosis were significantly and strikingly different from those without (p = 0.0064), suggesting that CPA development severely affects clinical outcome. Multivariate logistic regression analysis revealed that the use of systemic steroids (p = 0.0189) and cavity (p = 0.0207) were independent risk factors for the progression to CPA. Considering the high mortality rate of CPA in NTM-PD, early diagnosis and treatment are essential to improve outcomes for NTM-PD patients. Full article

Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmonary disease with species diversity showing significant regional variation. In the United States, Hawai’i shows the highest rate of NTM pulmonary disease. The need for improved understanding of NTM reservoirs led us to identify NTM from patient respiratory specimens and compare NTM diversity between outdoor and indoor locations in Hawai’i. A total of 545 water biofilm samples were collected from 357 unique locations across Kaua’i (n = 51), O’ahu (n = 202), Maui (n = 159), and Hawai’i Island (n = 133) and divided into outdoor (n = 179) or indoor (n = 366) categories. rpoB sequence analysis was used to determine NTM species and predictive modeling applied to develop NTM risk maps based on geographic characteristics between environments. M. chimaera was frequently identified from respiratory and environmental samples followed by M. chelonae and M. abscessus; yet significantly less NTM were consistently recovered from outdoor compared to indoor biofilms, as exemplified by showerhead biofilm samples. While the frequency of M. chimaera recovery was comparable between outdoor and indoor showerhead biofilms, phylogenetic analyses demonstrate similar rpoB gene sequences between all showerhead and respiratory M. chimaera isolates, supporting outdoor and indoor environments as possible sources for pulmonary M. chimaera infections. Full article

Nontuberculous mycobacteria constitute a subgroup among the Mycobacterium genus, a genus of Gram-positive bacteria that includes numerous pathogenic bacteria. In the present study, Mycobacterium spp. were detected in natural water samples from two Austrian rivers (Kamp and Wulka) using three different primers and PCR procedures for the identification of the 16S rRNA and hsp65 genes. Water samples were collected from the Kamp (45 samples) and Wulka (25 samples) in the summer and winter of 2018 and 2019. Molecular evidence showed a high prevalence of Mycobacterium sp. in these rivers with prevalence rates estimated at approximately 94.3% across all rivers. The present study represents the first survey into the prevalence of Mycobacterium sp. in natural water in Austria. Because nontuberculous mycobacteria have known pathogenic potential, including zoonotic, these findings may have implications for health management and public health. Full article

The Mycobacterium avium complex includes two closely related species, Mycobacterium avium and Mycobacterium intracellulare. They are opportunistic pathogens in humans and responsible for severe disease in a wide variety of animals. Yet, little is known about factors involved in their pathogenicity. Here, we identified, purified and characterized adhesins belonging to the heparin-binding hemagglutinin (HBHA) and laminin-binding protein (LBP) family from M. intracellulare ATCC13950 and examined clinical isolates from patients with different pathologies associated with M. intracellulare infection for the presence and conservation of HBHA and LBP. Using a recombinant derivative strain of M. intracellulare ATCC13950 producing green fluorescent protein and luciferase, we found that the addition of heparin inhibited mycobacterial adherence to A549 cells, whereas the addition of laminin enhanced adherence. Both HBHA and LBP were purified by heparin-Sepharose chromatography and their methylation profiles were determined by mass spectrometry. Patients with M. intracellulare infection mounted strong antibody responses to both proteins. By using PCR and immunoblot analyses, we found that both proteins were highly conserved among all 17 examined clinical M. intracellulare isolates from patients with diverse disease manifestations, suggesting a conserved role of these adhesins in M. intracellulare virulence in humans and their potential use as a diagnostic tool. Full article

The spread of carbapenem-resistant Enterobacteriaceae (CRE) has been enabled by the lack of control measures directed at carriers of multidrug-resistant organisms in healthcare settings. Screening patients for asymptomatic colonization on the one hand, and implementation of contact precautions on the other hand, reduces patient-to-patient transmission. Screening plates represents a relatively low-cost method for isolating CRE from rectal swabs; however, molecular assays have become widely available. This study compared the performance of four commercial molecular platforms in detecting clinically significant carbapenemase genes versus routine screening for CRE. A total of 1015 non-duplicated rectal swabs were cultured on a chromogenic carbapenem-resistant selective medium. All growing Enterobacteriaceae strains were tested for carbapenemase-related genes. The same specimens were processed using the following molecular assays: Allplex™ Entero-DR, Amplidiag^® CarbaR + MCR, AusDiagnostics MT CRE EU, and EasyScreen™ ESBL/CPO. The prevalence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae detected by swab culture was 2.2%, while organisms producing oxacillinase (OXA)-48 and metallo-β-lactamases were infrequent. The cost of CRE-related infection control precautions, which must be kept in place while waiting for screening results, are significant, so the molecular tests could become cost-competitive, especially when the turnaround time is decreased dramatically. Molecular assays represent a powerful diagnostic tool as they allow the rapid detection of the most clinically relevant carbapenemases. Full article

Mycobacterium avium subspecies paratuberculosis (Map) was monitored by quantitative PCR over a range of temporal and spatial scales in the River Tywi catchment. This study shows the persistence of Map over a 10-year period with little change, which correlates with the recognised levels of Johne’s disease in British herds over that period (aim 1). Map was quantified within the river at up to 10⁸ cell equivalents L⁻¹ and was shown to be consistently present when monitored over finer timescales (aim 4). Small wastewater treatment plants where the ingress of human-associated Map might be expected had no significant effect (aim 2). Map was found for the first time to be located in natural river foams providing another route for spread via aerosols (aim 5). This study provides evidence for the environmental continuum of Map from the grazing infected animal via rain driven runoff through field drains and streams into main rivers; with detection at a high frequency throughout the year. Should Map need to be monitored in the future, we recommend that weekly or monthly sampling from a fixed location on a river will capture an adequate representation of the flow dynamics of Map in a catchment (aim 3). The human exposure to Map during this process and its impact on human health remains unquantified. Full article

Non-tuberculous mycobacteria (NTM) are paradigmatic colonizers of the total environment, circulating at the interfaces of the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere. Their striking adaptive ecology on the interconnection of multiple spheres results from the combination of several biological features related to their exclusive hydrophobic and lipid-rich impermeable cell wall, transcriptional regulation signatures, biofilm phenotype, and symbiosis with protozoa. This unique blend of traits is reviewed in this work, with highlights to the prodigious plasticity and persistence hallmarks of NTM in a wide diversity of environments, from extreme natural milieus to microniches in the human body. Knowledge on the taxonomy, evolution, and functional diversity of NTM is updated, as well as the molecular and physiological bases for environmental adaptation, tolerance to xenobiotics, and infection biology in the human and non-human host. The complex interplay between individual, species-specific and ecological niche traits contributing to NTM resilience across ecosystems are also explored. This work hinges current understandings of NTM, approaching their biology and heterogeneity from several angles and reinforcing the complexity of these microorganisms often associated with a multiplicity of diseases, including pulmonary, soft-tissue, or milliary. In addition to emphasizing the cornerstones of knowledge involving these bacteria, we identify research gaps that need to be addressed, stressing out the need for decision-makers to recognize NTM infection as a public health issue that has to be tackled, especially when considering an increasingly susceptible elderly and immunocompromised population in developed countries, as well as in low- or middle-income countries, where NTM infections are still highly misdiagnosed and neglected. Full article

The Mycobacteriaceae constitute a family of varied Gram-positive organisms that include a large number of pathogenic bacteria. Among these, non-tuberculous mycobacteria are endemic worldwide and have been associated with infections in a large number of organisms, including humans and other mammals and reptiles, as well as fish. In this review, we summarize the most recent findings regarding this group of pathogens in fish. There, four species are most commonly associated with disease outbreaks: Mycobacterium marinum, the most common of these fish mycobacterial pathogens, Mycobacterium fortuitum, Mycobacterium gordonae, and Mycobacterium chelonae. These bacteria have a broad host range: they are zoonotic, and infections have been reported in a large number of fish species. The main route of entry of the bacterium into the fish is through the gastrointestinal route, and the disease is associated with ulcerative dermatitis as well as organomegaly and the development of granulomatous lesions in the internal organs. Mycobacteriaceae are slow-growing and fastidious and isolation is difficult and time consuming and diagnostic is mostly performed using serological and molecular tools. Control of the disease is also difficult: there is currently no effective vaccine and infections react poorly to antibiotherapy. For this reason, more research is needed on the subject of these vexing pathogens. Full article

Mycobacterium avium subsp. paratuberculosis (MAP) is an understudied pathogen worldwide with continuous implications in human autoimmune diseases (ADs). The awareness of MAP appears to be low in many places and its research is at infant stage in many countries. The lack of worldwide coverage of the MAP research landscape calls for urgent research attention and prioritization. This present study aimed to assess MAP global research productivity with an emphasis on its implications in ADs via bibliometric and growth analytic frameworks from authors, countries, institutions, international, disciplines and collaboration network perspectives. MAP primary articles were retrieved from the Scopus database and the Web of Science from 1911 to 2019 via title-specific algorithm. Analytic results of dataset yielded a total of 3889 articles from 581 journals and 20.65 average citations per documents. The annual growth rate of MAP research for the period was 6.31%. Based on a country’s productivity (articles (%), freq. of publication (%)), the USA (887 (22.81%), 26.72%), and Australia (236 (6.07%), 6.07%) ranked the top 2 countries but Egypt and Germany had the highest average growth rate (AGR, 170%) in the last 3 years. MAP studies are generally limited to Europe, Australia, Asia, South America and few nations in Africa. It had positive growth rate (30%–100%) in relation to type 1 diabetes mellitus and rheumatoid arthritis ADs; food science and technology, immunology, agriculture, pathology, and research and experimental medicine, wildlife, environments, virulence, disease resistance, meat and meat products, osteopontin, waste milk and slurry/sludge digestion subjects; but negative growth (−130% to −30%) in ulcerative colitis and Parkinson’s disease and no growth in multiple sclerosis, sarcoidosis, thyroid disorders, psoriasis, and lupus. The mapping revealed a gross lack of collaboration networking in terms of authorship, (intra- and inter-) nationally and institutionally with a generalized collaboration index of 1.82. In conclusion, inadequate resources-, knowledge- and scientific-networking hampered growth and awareness of MAP research globally. The study recommends further research to strengthen evidence of MAP’s epidemiologic prevalence in ADs and proffer practical solution(s) for drug development and point-of-care diagnostics amongst other extended themes. Full article

In recent decades, the incidence and prevalence of nontuberculous mycobacteria (NTM) have greatly increased, becoming a major worldwide public health problem. Among numerous NTM species, the Mycobacterium avium complex (MAC) is the most predominant species, causing disease in humans. MAC is recognized as a ubiquitous microorganism, with contaminated water and soil being established sources of infection. However, the reason for the recent increase in MAC-associated disease has not yet been fully elucidated. Furthermore, human MAC infections are associated with a variety of infection sources. To improve the determination of infection sources and epidemiology of MAC, feasible and reliable genotyping methods are required to allow for the characterization of the epidemiology and biology of MAC. In this review, we discuss genotyping methods, such as pulsed-field gel electrophoresis, a variable number of tandem repeats, mycobacterial interspersed repetitive-unit-variable number of tandem repeats, and repetitive element sequence-based PCR that have been applied to elucidate the association between the MAC genotypes and epidemiological dominance, clinical phenotypes, evolutionary process, and control measures of infection. Characterizing the association between infection sources and the epidemiology of MAC will allow for the development of novel preventive strategies for the effective control of MAC infection. Full article

Mycobacterium uberis (M. uberis) is a recently described non-tuberculous mycobacterium phylogenetically close to Mycobacterium leprae (M. leprae) and Mycobacterium lepromatosis (M. lepromatosis). This pathogen classically causes nodular thelitis in cattle and goats. Here, we discuss what seems to be the first described case of M. uberis infection in a novel anatomical site, in the proximal or distal position (information not available) of the radius/ulna area of a cow. As this case was discovered in the framework of bovine tuberculosis (bTB) surveillance program in France, this type of infection could interfere with the screening and diagnostic tools employed for bTB. Full article