Dataset Information

High rate of reinfection and possible transmission of Mycobacterium avium complex in Northeast Thailand.

ABSTRACT: The Mycobacterium avium complex (MAC) includes two main species of non-tuberculous mycobacteria (NTM), M. avium and Mycobacterium intracellulare. These can cause serious disease, especially in immunocompromised patients. Little information is available concerning genetic diversity of NTM. We used multilocus sequence typing (MLST) based on a highly discriminative gene set to analyze MAC serially isolated from patients to determine the rate of MAC reinfection. Genomic DNA was sequenced from 49 MAC isolates (15 cases comprised of 11 true infections and 4 instances of colonization). More than half of the MAC isolates tested were found to be multidrug resistant. The discriminatory power was assessed of 24 house-keeping genes (fusA, atpD, pheT, glnA, topA, secA, argH, glpK, murC, cya, pta, rrl, rrs, hsp65, rpoB, 16S-23S rRNA ITS, recF, lipT, pepB, gnd, aspB, groEL, sodA and est) previously used for genotyping of MAC and other NTM. Seven genes (fusA, secA, rpoB, hsp65, 16S rRNA, 23S rRNA, 16S-23S rRNA ITS) had a discriminatory power index higher than 0.9 and were included in the optimized set that we used. This set was significantly better for genotyping and diagnosis of MAC than previously used 4-gene, 5-gene and 9-gene sets. MLST using our 7-gene set indicated that the rate of reinfection was 54.55% (6/11 cases). Persistent infections (n = 5 cases, 45.45%) were found. A changing of clone in the same patient was found in 1/4 (25%) of the colonization cases. Two small clusters of possible MAC transmission between humans were found. Our study demonstrated that the high frequency of apparent treatment failure of MAC might be artefactual, as a consequence of a high rate of MAC reinfection in Thai population. Our useful highly discriminative gene set for MAC species and clonal strain analysis could be further applied for the diagnosis and patient management.

SUBMITTER: Boonjetsadaruhk W

PROVIDER: S-EPMC8855214 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High rate of reinfection and possible transmission of Mycobacterium avium complex in Northeast Thailand.

Boonjetsadaruhk Wicharajit W Kaewprasert Orawee O Nithichanon Arnone A Ananta Pimjai P Chaimanee Prajuab P Salao Kanin K Phoksawat Wisitsak W Laohaviroj Marut M Sirichoat Auttawit A Fong Yang Y Wongwajana Suwin S Namwat Wises W Lulitanond Viraphong V Chetchotisakd Ploenchan P Faksri Kiatichai K

One health (Amsterdam, Netherlands) 20220211

The Mycobacterium avium complex (MAC) includes two main species of non-tuberculous mycobacteria (NTM), M. avium and Mycobacterium intracellulare. These can cause serious disease, especially in immunocompromised patients. Little information is available concerning genetic diversity of NTM. We used multilocus sequence typing (MLST) based on a highly discriminative gene set to analyze MAC serially isolated from patients to determine the rate of MAC reinfection. Genomic DNA was ...[more]

PMID: 35198722

Similar Datasets

Project description: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.

Project description:RationaleMycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease.ObjectivesThe objectives of this study were to assess the susceptibility, immunologic and histopathologic responses of the common marmoset (Callithrix jacchus) to M. avium complex pulmonary infection.Methods7 adult female marmosets underwent endobronchial inoculation with 108 colony-forming units of M. intracellulare and were monitored for 30 or 60 days. Chest radiograph was assessed at baseline (prior to infection) and at the time of sacrifice (30 days for 3 animals and 60 days for 4 animals), and bronchoalveolar lavage cytokines, histopathology and cultures of the bronchoalveolar lavage, lungs, liver and kidney were assessed at time of sacrifice. Serum cytokines were monitored at baseline and weekly for 30 days for all animals and at 60 days for those alive. Group differences in serum cytokine measurements between those that tested positive versus negative for the M. intracellulare infection were assessed using a series of linear mixed models.Measurements and main resultsFive of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare. Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation, while at 60 days there were fewer inflammatory changes but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection, with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14-21 days after inoculation.ConclusionEndobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.

Dataset Information

High rate of reinfection and possible transmission of Mycobacterium avium complex in Northeast Thailand.

Publications

High rate of reinfection and possible transmission of <i>Mycobacterium avium</i> complex in Northeast Thailand.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets