Comparative Genomics of Mycobacterium avium Complex Reveals Signatures of Environment-Specific Adaptation and Community Acquisition

Keen, Eric C; Choi, Joo-Hee; Wallace, Meghan A.; Azar, Michelle; Mejía-Chew, Carlos; Mehta, Shail; Bailey, Thomas C.; Caverly, Lindsay J.; Burnham, Carey‐Ann D.; Dantas, Gautam

doi:10.1128/msystems.01194-21

Cited by 10 publications

(5 citation statements)

References 102 publications

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“…In particular, isolates from humans and animals differed. Similarly, this has also been demonstrated in isolates from human patients and their environment [ 39 ]. In the United States, in central North Carolina, a higher incidence of pulmonary mycobacteriosis was found to be influenced by housing in hydric and acidic soils [ 40 ].…”

Section: Searching For Patients’ Predisposition To Infection and Sour...mentioning

confidence: 53%

Nontuberculous Mycobacteria: Ecology and Impact on Animal and Human Health

2022

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Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses in humans and animals. The sources of infections often remain undetected except for soil- or water-borne, water-washed, water-based, or water-related infections caused by groups of the Mycobacterium (M.) avium complex; M. fortuitum; and other NTM species, including M. marinum infection, known as fish tank granuloma, and M. ulcerans infection, which is described as a Buruli ulcer. NTM could be considered as water-borne, air-borne, and soil-borne pathogens (sapronoses). A lot of clinically relevant NTM species could be considered due to the enormity of published data on permanent, periodic, transient, and incidental sapronoses. Interest is currently increasing in mycobacterioses diagnosed in humans and husbandry animals (esp. pigs) caused by NTM species present in peat bogs, potting soil, garden peat, bat and bird guano, and other matrices used as garden fertilizers. NTM are present in dust particles and in water aerosols, which represent certain factors during aerogenous infection in immunosuppressed host organisms during hospitalization, speleotherapy, and leisure activities. For this Special Issue, a collection of articles providing a current view of the research on NTM—including the clinical relevance, therapy, prevention of mycobacterioses, epidemiology, and ecology—are addressed.

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Section: Searching For Patients’ Predisposition To Infection and Sour...mentioning

confidence: 53%

Nontuberculous Mycobacteria: Ecology and Impact on Animal and Human Health

2022

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“…The genetic variability of isolated strains in different regions of the world cannot be excluded either. Although different species and subspecies in the MAC complex do not have identical MIC 50 and MIC 90 values [ 94 ], the five lineages of M. avium may also differ in the level of intrinsic resistance to antibacterial drugs [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

Zimenkov

2022

Antibiotics

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Non-tuberculous mycobacteria are widely distributed in environments and are capable of infecting humans, particularly those with a compromised immune system. The most prevalent species that cause nontuberculous mycobacterial lung diseases are slow-growing bacteria from the Mycobacterium avium complex (MAC), mainly M. avium or M. intracellulare. The key treatment of MAC infections includes macrolides, ethambutol, and rifampicin; however, the therapy outcomes are unsatisfactory. Phenotypic drug susceptibility testing is a conditional recommendation prior to treatment, and critical concentrations for clarithromycin, amikacin, moxifloxacin, and linezolid have been established. In this review, data from studies on the determination of MIC of clinical isolates using the broth microdilution method were summarized. A significant variation in the MIC distributions from different studies was found. The main reasons could impact the findings: insufficient reproducibility of the phenotypic testing and variation in species lineages identified in different laboratories, which could have various intrinsic susceptibility to drugs. For most of the drugs analyzed, the MICs are too high, which could undermine the treatment efficiency. Further improvement of treatment outcomes demands the validation of microbiological resistance criteria together with the identification of molecular mechanisms of resistance.

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“…The genome of MAC was relatively large, consisting of approximately 5.8 Mbp. Studies of the MAC genome has identified numerous genes and pathways involved in virulence and drug resistance as well as variation in gene content and organization among different strains, which could contribute to differences in virulence and drug resistance [55,56]. Understanding the functions of these virulence factors is crucial for the development of effective therapies against mycobacterial infections.…”

Section: Plos Onementioning

confidence: 99%

Phenotypic drug-susceptibility profiles and genetic analysis based on whole-genome sequencing of Mycobacterium avium complex isolates in Thailand

Sirichoat,

Kaewprasert,

Hinwan

et al. 2023

PLoS ONE

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Mycobacterium avium complex (MAC) infections are a significant clinical challenge. Determining drug-susceptibility profiles and the genetic basis of drug resistance is crucial for guiding effective treatment strategies. This study aimed to determine the drug-susceptibility profiles of MAC clinical isolates and to investigate the genetic basis conferring drug resistance using whole-genome sequencing (WGS) analysis. Drug-susceptibility profiles based on minimum inhibitory concentration (MIC) assays were determined for 38 MAC clinical isolates (12 Mycobacterium avium and 26 Mycobacterium intracellulare). Mutations associated with drug resistance were identified through genome analysis of these isolates, and their phylogenetic relationships were also examined. Drug resistance, based on MIC values, was most commonly observed for moxifloxacin (81.6%), followed by linezolid (78.9%), clarithromycin (44.7%) and amikacin (36.8%). We identified specific mutations associated with resistance to amikacin. These include the rrs mutation at C464T in amikacin intermediate-resistance M. avium, and two mutations at T250A and G1453T in amikacin non-susceptible M. intracellulare. Mutations in rrl at A2058G, A2059C and A2059G were potentially linked to clarithromycin resistance. MAC clinical isolates not susceptible to linezolid exhibited mutations in rplC at G237C and C459T, as well as two rplD mutations at G443A and A489G. GyrB substitution Thr521Ala (T521A) was identified in moxifloxacin non-susceptible isolates, which may contribute to this resistance. A phylogeny of our MAC isolates revealed high levels of genetic diversity. Our findings suggest that the standard treatment regimen for MAC infections using moxifloxacin, linezolid, clarithromycin and amikacin may be driving development of resistance, potentially due to specific mutations. The combination of phenotypic and genotypic susceptibility testing can be valuable in guiding the clinical use of drugs for the treatment of MAC infections.

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Comparative Genomics of Mycobacterium avium Complex Reveals Signatures of Environment-Specific Adaptation and Community Acquisition

Abstract: Members of the Mycobacterium avium complex (MAC), a group of mycobacteria encompassing M. avium and its closest relatives, are omnipresent in natural environments and emerging pathogens of humans and animals. MAC infections are difficult to treat, sometimes fatal, and increasingly common.

Cited by 10 publications

References 102 publications

Nontuberculous Mycobacteria: Ecology and Impact on Animal and Human Health

Nontuberculous Mycobacteria: Ecology and Impact on Animal and Human Health

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

Phenotypic drug-susceptibility profiles and genetic analysis based on whole-genome sequencing of Mycobacterium avium complex isolates in Thailand

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