Abstract

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.

Highlights

  • Mycobacterium avium complex (MAC), a slow-growing mycobacterium that inhabits a wide range of sources, such as soil, water, domestic and wild animals, and foodstuffs, causes various forms of disease in humans, other mammals, and birds [1]

  • MAC differs in virulence and ecology within the constituent bacteria, among which species such as M. avium subsp. avium (MAA), MAP, M. avium subsp. hominissuis (MAH), and M. avium subsp. silvaticum (MAS) are strict pathogens; M. intracellulare is considered to be an environmental bacterium that is widely distributed in soil and water [24]

  • Comparative mycobacterial interspersed repetitive-unit (MIRU)-variable number of tandem repeats (VNTR) analysis of M. avium and MAP revealed that the 183 MAP isolates were grouped into only 21 types, whereas 82 M. avium isolates were grouped into 30 types without overlapping patterns with MAP, demonstrating that the newly developed MIRU-VNTR genotyping technique had a high discrimination power for M. avium [69]

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Summary

Introduction

Mycobacterium avium complex (MAC), a slow-growing mycobacterium that inhabits a wide range of sources, such as soil, water, domestic and wild animals, and foodstuffs, causes various forms of disease in humans, other mammals, and birds [1]. A study published in the early 1990s revealed that the incidence of MAC in AIDS patients ranged from 20–40% [8,9]. These findings indicate that MAC is a representative microorganism among NTM species which cause human disease. Various epidemiological studies on MAC have been conducted using different genotyping techniques, there is still a lack of literature presenting the epidemiological characteristics, biology, and origins of MAC from humans, animals, and environmental sources using definitive genotyping techniques. In this review, we discuss the application of the major genotyping methods for the characterization of MAC, including restriction fragment length polymorphisms (RFLP), pulsed-field gel electrophoresis (PFGE), variable number of tandem repeats (VNTR), mycobacterial interspersed repetitive-unit (MIRU)-VNTR, and repetitive element sequence-based PCR (rep-PCR), and deal with the associations of genotypes with epidemiological investigation, diagnosis, clinical phenotypes, evolution, transmission mode, and prevention of MAC in order to control these organisms more effectively

Significance of Molecular Genotyping Methods Applied to MAC
PFGE for MAC and Their Implications in Epidemiological Studies
Investigation of MAC for Co-Infection and Relapse
Comparison of PFGE with Other Genotyping Methods
VNTR for MAC and Their Implications in Epidemiological Studies
Identification of VNTR Loci and Development of VNTR Techniques
Application of VNTR Method for Clinical and Epidemiological Investigations
Geographical Relationship between Bacterial Strains Belonging to MAC
Comparison of VNTR Using Other Genetic Typing Methods
MIRUs 16 VNTRs
Findings
Conclusions and Perspectives
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