scholarly journals Five-year microevolution of a multidrug-resistant Mycobacterium tuberculosis strain within a patient with inadequate compliance to treatment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Darío A. Fernandez Do Porto ◽  
Johana Monteserin ◽  
Josefina Campos ◽  
Ezequiel J. Sosa ◽  
Mario Matteo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Whole Genome Sequence ◽  
Intermittent Therapy ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Short Term ◽  
Depth Analysis

Abstract Background Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution —the genetic variability of M. tuberculosis at short time scales— of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. Case presentation In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5′ untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. Conclusions This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.

scholarly journals Five-year Microevolution of a Multidrug-Resistant Mycobacterium Tuberculosis Strain within a Patient with Inadequate Compliance to Treatment.

2021 ◽  
Author(s):  
Dario Fernández Do Porto ◽  
Johana Monteserin ◽  
Josefina Campos ◽  
Ezequiel J Sosa ◽  
Mario Matteo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Treatment Compliance ◽  
Whole Genome Sequence ◽  
Intermittent Therapy ◽  
Whole Genome ◽  
Short Term ◽  
Depth Analysis

Abstract BackgroundWhole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution —the genetic variability of M. tuberculosis at short time scales— of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported.Case Presentations In this work, we applied whole genome sequencing for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium. tuberculosis isolates obtained from a patient within 57-month of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patience, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy.ConclusionsThis report highlights the relevance of whole-genome sequencing in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.

scholarly journals Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bénedith Oben ◽  
Guy Froyen ◽  
Kylee H. Maclachlan ◽  
Daniel Leongamornlert ◽  
Federico Abascal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Monoclonal Gammopathy ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Driver Genes ◽  
Smoldering Myeloma ◽  
Undetermined Significance

AbstractMultiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.

scholarly journals Whole-Genome Sequencing Analysis of Serially Isolated Multi-Drug and Extensively Drug Resistant Mycobacterium tuberculosis from Thai Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160992 ◽  
Author(s):  
Kiatichai Faksri ◽  
Jun Hao Tan ◽  
Areeya Disratthakit ◽  
Eryu Xia ◽  
Therdsak Prammananan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Spoligotyping and whole-genome sequencing analysis of lineage 1 strains of Mycobacterium tuberculosis in Da Nang, Vietnam

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186800 ◽  
Author(s):  
Minako Hijikata ◽  
Naoto Keicho ◽  
Le Van Duc ◽  
Shinji Maeda ◽  
Nguyen Thi Le Hang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Sequencing Analysis

scholarly journals Insight into the PZA resistance whole genome of Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan

2020 ◽  
Author(s):  
Muhammad Tahir Khan ◽  
Sajid Ali ◽  
anwar Sheed Khan ◽  
Arif Ali ◽  
Abbas Khan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Candidate Genes ◽  
Genome Sequencing ◽  
Metabolic Model ◽  
Whole Genome Sequence ◽  
Public Health Issue ◽  
Drug Candidate ◽  
Whole Genome ◽  
Khyber Pakhtunkhwa

Abstract Background Tuberculosis (TB) is a global public health issue, getting worse due to emergence of resistance. Pyrazinamide (PZA) is first-line antimicrobial drugs used against non-replicated Mycobacterium tuberculosis (MTB). Data is scarce about whole genome sequencing of PZA resistance (PZA-R) in Khyber Pakhtunkhwa (KP) province of high burden country, Pakistan. In the current study we aimed to find the most common mutations in PZA-R MTB isolates in association with other candidate genes in a whole genome sequence (WGS). Samples were collected from TB suspects and drug susceptibility testing (DST) was performed according according to the WHO standards. The resistant samples were subjected for whole genome sequencing (WGS). The sequence data was through MTBseq and Total Genotyping Solution for Mycobacterium tuberculosis (TGS-TB). Metabolic model was analyzed, using RAST server. Results Among the three whole genome sequences, (NCBI BioProject Accession: PRJNA629298, PRJNA629388) 1997, 1162, and 2053 mutations including indel, was detected. Diverse variability has been detected in the membrane proteins PE and PPE, modulating the host immune response. Nine mutations in coding and promotor region have been detected in pncA with one novel (T-4C) variants. Mutations in the other drug candidate genes, KatG, rpoB have also been detected. Conclusion The metabolic model shows a distinct property. Diversity of variants has been detected in majority of MTB essential genes, functions from cell growth to cell signaling. The current study provides useful information, associated with geographic specific strains for biomarkers development and better management of drug resistance isolates.

scholarly journals Whole Genome Sequence Analysis of SARS-CoV-2 Strains Circulating in Malaysia During First Wave and Early Second Wave of Infections.

2020 ◽  
Author(s):  
Zarina Mohd Zawawi ◽  
Jeyanthi Suppiah ◽  
Jeevanathan Kalyanasundram ◽  
Muhammad Afif Azizan ◽  
Shuhaila Mat-Sharani ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome Sequence ◽  
Health Concern ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Full Genome ◽  
Sequencing Data ◽  
Genome Sequences ◽  
Synonymous Mutations

Abstract Background: Since December 2019, the outbreak of COVID-19 has raised a great public health concern globally. Here, we report the whole genome sequencing analysis of SARS-CoV-2 strains in Malaysia isolated from six patients diagnosed with COVID-19.Methods: The SARS-CoV-2 viral RNA extracted from clinical specimens and isolates were subjected to whole genome sequencing using NextSeq 500 platform. The sequencing data were assembled to full genome sequences using Megahit and phylogenetic tree was constructed using Mega X software.Results: Six full genome sequences of SARS-CoV-2 comprising of strains from 1st wave (25th January 2020) and 2nd wave (27th February 2020) infection were obtained. Downstream analysis demonstrated diversity among the Malaysian strains with several synonymous and non-synonymous mutations in four of the six cases, affecting the genes M, orf1ab, and S of the SARS-CoV-2 virus. The phylogenetic analysis revealed viral genome sequences of Malaysian SARS-CoV-2 strains clustered under the ancestral Type B.Conclusion: This study comprehended the SARS-CoV-2 virus evolution during its circulation in Malaysia. Continuous monitoring and analysis of the whole genome sequences of confirmed cases would be crucial to further understand the genetic evolution of the virus.

scholarly journals Whole-genome sequencing analysis of multidrug-resistant Mycobacterium tuberculosis from Java, Indonesia

2020 ◽  
Vol 69 (7) ◽  
pp. 1013-1019
Author(s):  
Tryna Tania ◽  
Pratiwi Sudarmono ◽  
R. Lia Kusumawati ◽  
Andriansjah Rukmana ◽  
Wahyu Agung Pratama ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Major Public Health Problem ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Mdr Tb

Introduction. Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem globally, including in Indonesia. Whole-genome sequencing (WGS) analysis has rarely been used for the study of TB and MDR-TB in Indonesia. Aim. We evaluated the use of WGS for drug-susceptibility testing (DST) and to investigate the population structure of drug-resistant Mycobacterium tuberculosis in Java, Indonesia. Methodology. Thirty suspected MDR-TB isolates were subjected to MGIT 960 system (MGIT)-based DST and to WGS. Phylogenetic analysis was done using the WGS data. Results obtained using MGIT-based DST and WGS-based DST were compared. Results. Agreement between WGS and MGIT was 93.33 % for rifampicin, 83.33 % for isoniazid and 76.67 % for streptomycin but only 63.33 % for ethambutol. Moderate WGS–MGIT agreement was found for second-line drugs including amikacin, kanamycin and fluoroquinolone (73.33–76.67 %). MDR-TB was more common in isolates of the East Asian Lineage (63.3%). No evidence of clonal transmission of DR-TB was found among members of the tested population. Conclusion. Our study demonstrated the applicability of WGS for DST and molecular epidemiology of DR-TB in Java, Indonesia. We found no transmission of DR-TB in Indonesia.

scholarly journals Whole-Genome Sequence of Streptococcus tigurinus Strain osk_001, Isolated from Postmortem Material

2017 ◽  
Vol 5 (35) ◽  
Author(s):  
Hidenori Yoshizawa ◽  
Daisuke Motooka ◽  
Ryuichi Katada ◽  
Yuki Matsumoto ◽  
Shota Nakamura ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Novel Species ◽  
Infected Tissue ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Virulent Strains ◽  
Highly Virulent

ABSTRACT Streptococcus tigurinus was recently described as a novel species, and some strains are highly virulent. We detected S. tigurinus in infected tissue sampled by necropsy. In order to characterize and confirm the virulence of this species, whole-genome sequencing of the pure cultured bacterium was performed. We found that the strain has specific and unique genetic elements contained in highly virulent strains of S. tigurinus.

scholarly journals Whole-Genome Sequence of the Mycoplasma mucosicanis Type Strain

2019 ◽  
Vol 8 (41) ◽  
Author(s):  
Rebecca L. Tallmadge ◽  
Patrick K. Mitchell ◽  
Renee Anderson ◽  
Rebecca Franklin-Guild ◽  
Laura B. Goodman
Keyword(s):  
Whole Genome Sequencing ◽  
Clinical Significance ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Diagnostic Tests ◽  
Type Strain ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type

Whole-genome sequencing of Mycoplasma mucosicanis type strain 1642 was performed to support efforts to better understand the clinical significance of Mycoplasma infection in canine health. The availability of this sequence will also further the development of highly specific diagnostic tests.

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