Mycobacterium tuberculosis polyclonal infections and microevolution identified by MIRU-VNTRs in an epidemiological study

Streit, Elisabeth; Millet, Julie; Rastogi, Nalin

doi:10.1016/j.ijmyco.2015.05.005

Cited by 18 publications

(16 citation statements)

References 21 publications

(37 reference statements)

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“…Cultures detected as mixed infection by at least two methods were considered Polyclonal. [27] None of the follow up samples gave evidence for microevolution. SNP genotyping was used for the first time for detection of Polyclonal infections.…”

Section: Identification Of Mixed Infections By Miru-vntr Typing and Smentioning

confidence: 96%

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Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

Pandey

Bhatnagar²,

Sachdeva

et al. 2020

PLoS ONE

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Background Mixed/polyclonal infections due to different genotypes are reported in Tuberculosis. The current study was designed to understand the fate of mixed infections during the course of treatment and follow-up and its role in disease pathogenesis. Methods Sputum samples were collected on 0,1,2,3,6,12 and 24 months from 157 treatment-naïve patients, cultures subjected to Drug-Susceptibility-testing (MGIT 960), spoligotyping, MIRU-VNTR and SNP genotyping. All isolated colonies on thin layer agar (7H11) were subjected to spoligotyping. Findings One thirty three baseline cultures were positive (133/157, 84.7%), 43(32.3%) had mixture of genotypes. Twenty-four of these patients (55.8%) showed change in genotype while six showed different drug-susceptibility patterns while on treatment. Twenty-three (53.5%) patients with polyclonal infections showed resistance to at least one drug compared to 10/ 90 (11.1%) monoclonal infections (P<0.0001). Eight patients had recurrent TB, two with a new genotype and two with altered phenotypic DST. Conclusions The coexistence of different genotypes and change of genotypes during the same disease episode, while on treatment, confirms constancy of polyclonal infections. The composition of the mixture of genotypes and the relative predominance may be missed by culture due to its limit of detection. Polyclonal infections in TB could be a rule rather than exception and challenges the age-old dogma of reactivation/reinfection.

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Section: Identification Of Mixed Infections By Miru-vntr Typing and Smentioning

confidence: 96%

“…MIRU-VNTR typing uses presence of double alleles in two or more VNTR loci for detection of mixed infections. [27] SNP-genotyping defined mixed infection if two SNP's were positive at the same time. [26] Single colony spoligotyping was also used to detect mixed infections.…”

Section: Molecular Genotypingmentioning

confidence: 99%

Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

Pandey

Bhatnagar²,

Sachdeva

et al. 2020

PLoS ONE

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“…Following phylogenetic and Bayesian population structure analyses performed on this dataset led to the characterization of tentatively three new Beijing clonal complexes with phylogeographical specificities to previously unstudied geographical regions, proving the need for continued investigations with extended datasets worldwide. Lastly, as a spin-off of this larger study, we also studied the phenomenon of clonal heterogeneity (CH) defined as “inpatient” microevolution of an infecting clone, to explore if any given clonal complex could be more prone to variability (and subsequent geographical adaptability) among the involved isolates 21, 22 . Interestingly, CH cases exclusively mapped with ubiquitous Beijing lineages, suggesting higher adaptability.…”

Section: Introductionmentioning

confidence: 99%

New Mycobacterium tuberculosis Beijing clonal complexes in China revealed by phylogenetic and Bayesian population structure analyses of 24-loci MIRU-VNTRs

Zheng

Reynaud

Zhao

et al. 2017

Sci Rep

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Beijing lineage of Mycobacterium tuberculosis constitutes the most predominant lineage in East Asia. Beijing epidemiology, evolutionary history, genetics are studied in details for years revealing probable origin from China followed by worldwide expansion, partially linked to higher mutation rate, hypervirulence, drug-resistance, and association with cases of mixed infections. Considering huge amount of data available for 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats, we performed detailed phylogenetic and Bayesian population structure analyses of Beijing lineage strains in mainland China and Taiwan using available 24-loci MIRU-VNTR data extracted from publications or the SITVIT2 database (n = 1490). Results on genetic structuration were compared to previously published data. A total of three new Beijing clonal complexes tentatively named BSP1, BPS2 and BSP3 were revealed with surprising phylogeographical specificities to previously unstudied regions in Sichuan, Chongqing and Taiwan, proving the need for continued investigations with extended datasets. Such geographical restriction could correspond to local adaptation of these “ecological specialist” Beijing isolates to local human host populations in contrast with “generalist pathogens” able to adapt to several human populations and to spread worldwide.

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“…In mixed infections multiple strains of Mycobacterium tuberculosis (M. tuberculosis ) are retrieved from an individual patient1. Mycobacterial Interspersed Repetitive Unit- Variable Number Tandem Repeat (MIRU-VNTR) genotyping, widely applied in the molecular epidemiology of TB, eases the detection of mixed infections2. Based on MIRU-VNTR, mixed infections are defined by the presence of different MIRU-VNTR patterns at two or more loci in the same clinical samples, while clonal heterogeneity is defined as having different patterns at a single locus34.…”

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confidence: 99%

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

Kamakoli

Sadegh

Farmanfarmaei

et al. 2017

Sci Rep

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Mixed strain infections of Mycobacterium tuberculosis make diagnosis, treatment, and control of tuberculosis (TB) more difficult. This study was aimed to evaluate the relationship between mixed infections, antibiotic resistance patterns and treatment of TB patients. In this study, among 2850 suspected TB clinical samples, a total of ninety-six clinical samples from 66 TB confirmed patients were subjected to the 24-locus variable-number tandem repeat method to evaluate the prevalence of mixed infections. For all studied strains, 288 colonies (three individual clones for each sample) were isolated from different colonies and separately analyzed by the Drug Susceptibility Test (DST). For all patients, follow up was done after 6 months of treatment. Based on direct 24 loci MIRU-VNTR, in the 66 TB patients, 53% (35/66) showed mixed infection. In the mixed samples, 45.71% (16/35) showed different antibiotic resistant patterns. Among the mixed infection patients, eight (22.9%; 8/35) showed treatment failure after six- month therapy. Six of these non-treated patients (75%; 6/8) had different antibiotic resistant patterns. We conclude that mixed infections, have a negative impact on treatment of TB patients especially when co-infecting M. tuberculosis strains display heteroresistance.

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Mycobacterium tuberculosis polyclonal infections and microevolution identified by MIRU-VNTRs in an epidemiological study

Cited by 18 publications

References 21 publications

Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

New Mycobacterium tuberculosis Beijing clonal complexes in China revealed by phylogenetic and Bayesian population structure analyses of 24-loci MIRU-VNTRs

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

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