scholarly journals Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Francesc Coll ◽  
Ruth McNerney ◽  
Mark D Preston ◽  
José Afonso Guerra-Assunção ◽  
Andrew Warry ◽  
...  
Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1017
Author(s):  
Hirohisa Mekata ◽  
Tomohiro Okagawa ◽  
Satoru Konnai ◽  
Takayuki Miyazawa

Bovine foamy virus (BFV) is a member of the foamy virus family in cattle. Information on the epidemiology, transmission routes, and whole-genome sequences of BFV is still limited. To understand the characteristics of BFV, this study included a molecular survey in Japan and the determination of the whole-genome sequences of 30 BFV isolates. A total of 30 (3.4%, 30/884) cattle were infected with BFV according to PCR analysis. Cattle less than 48 months old were scarcely infected with this virus, and older animals had a significantly higher rate of infection. To reveal the possibility of vertical transmission, we additionally surveyed 77 pairs of dams and 3-month-old calves in a farm already confirmed to have BFV. We confirmed that one of the calves born from a dam with BFV was infected. Phylogenetic analyses revealed that a novel genotype was spread in Japan. In conclusion, the prevalence of BFV in Japan is relatively low and three genotypes, including a novel genotype, are spread in Japan.


2021 ◽  
Vol 9 (3) ◽  
pp. 5-10
Author(s):  
N.V. Kuznetsov ◽  
A.S. Lesonen ◽  
U.M. Markelov ◽  
E.D. Mikhailova

The article presents the results of predicting the dynamics of the spread of new cases of tuberculosis (TB) with multiple drug resistance (MDR) in the Republic of Karelia, as well as the costs of treating patients with tuberculosis, considering the different effectiveness of treatment. It has been demonstrated that while enhancing efficiency of treatment, due to the rapid determination of drug resistance by the method of polymerase chain reaction and a decrease in treatment gaps (using food kits), the effectiveness of treatment is significantly increased and the prevalence of MDR-TB decreases, which leads to significant budget savings.


Microbiology ◽  
2006 ◽  
Vol 152 (11) ◽  
pp. 3185-3196 ◽  
Author(s):  
Carlos Canchaya ◽  
Marcus J. Claesson ◽  
Gerald F. Fitzgerald ◽  
Douwe van Sinderen ◽  
Paul W. O'Toole

The genus Lactobacillus contains over 80 recognized species, and is characterized by a high level of diversity, reflected in its complex phylogeny. The authors' recent determination of the genome sequence of Lactobacillus salivarius means that five complete genomes of Lactobacillus species are available for comparative genomics: L. salivarius, L. plantarum, L. acidophilus, L. johnsonii and L. sakei. This paper now shows that there is no extensive synteny of the genome sequences of these five lactobacilli. Phylogeny based on whole-genome alignments suggested that L. salivarius was closer to L. plantarum than to L. sakei, which was closest to Enterococcus faecalis, in contrast to 16S rRNA gene relatedness. A total of 593 orthologues common to all five species were identified. Species relatedness based on this protein set was largely concordant with genome synteny-based relatedness. A Lactobacillus supertree, combining individual phylogenetic trees from each of 354 core proteins, had four main branches, comprising L. salivarius–L. plantarum; L. sakei; E. faecalis; and L. acidophilus–L. johnsonii. The extreme divergence of the Lactobacillus genomes analysed supports the recognition of new subgeneric divisions.


PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163746 ◽  
Author(s):  
Robert A. Power ◽  
Siva Davaniah ◽  
Anne Derache ◽  
Eduan Wilkinson ◽  
Frank Tanser ◽  
...  

2016 ◽  
Author(s):  
Robert A. Power ◽  
Siva Davaniah ◽  
Anne Derache ◽  
Eduan Wilkinson ◽  
Frank Tanser ◽  
...  

AbstractGenome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics.We performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naive to the respective treatment.GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting the ability of GWAS to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR.These results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pravech Ajawatanawong ◽  
Hideki Yanai ◽  
Nat Smittipat ◽  
Areeya Disratthakit ◽  
Norio Yamada ◽  
...  

Abstract Global Mycobacterium tuberculosis population comprises 7 major lineages. The Beijing strains, particularly the ones classified as Modern groups, have been found worldwide, frequently associated with drug resistance, younger ages, outbreaks and appear to be expanding. Here, we report analysis of whole genome sequences of 1170 M. tuberculosis isolates together with their patient profiles. Our samples belonged to Lineage 1–4 (L1–L4) with those of L1 and L2 being equally dominant. Phylogenetic analysis revealed several new or rare sublineages. Differential associations between sublineages of M. tuberculosis and patient profiles, including ages, ethnicity, HIV (human immunodeficiency virus) infection and drug resistance were demonstrated. The Ancestral Beijing strains and some sublineages of L4 were associated with ethnic minorities while L1 was more common in Thais. L2.2.1.Ancestral 4 surprisingly had a mutation that is typical of the Modern Beijing sublineages and was common in Akha and Lahu tribes who have migrated from Southern China in the last century. This may indicate that the evolutionary transition from the Ancestral to Modern Beijing sublineages might be gradual and occur in Southern China, where the presence of multiple ethnic groups might have allowed for the circulations of various co-evolving sublineages which ultimately lead to the emergence of the Modern Beijing strains.


2018 ◽  
Author(s):  
Sebastian M. Gygli ◽  
Peter M. Keller ◽  
Marie Ballif ◽  
Nicolas Blöchliger ◽  
Rico Hömke ◽  
...  

AbstractWhole genome sequencing allows rapid detection of drug-resistant M. tuberculosis isolates. However, high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data have thus far been lacking.We determined drug resistance profiles of 176 genetically diverse clinical M. tuberculosis isolates from Democratic Republic of the Congo, Ivory Coast, Peru, Thailand and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD BACTEC MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout. We compared phenotypic drug susceptibility results with predicted drug resistance profiles inferred by whole genome sequencing.Both phenotypic DST methods identically classified the strains into resistant/susceptible in 73-99% of the cases, depending on the drug. Changes in minimal inhibitory concentrations were readily explained by mutations identified by whole genome sequencing. Using the whole genome sequences we were able to predict quantitative drug resistance levels where wild type and mutant MIC distributions did not overlap. The utility of genome sequences to predict quantitative levels of drug resistance was partially limited due to incompletely understood mechanisms influencing the expression of phenotypic drug resistance. The overall sensitivity and specificity of whole genome-based DST were 86.8% and 94.5%, respectively.Despite some limitations, whole genome sequencing has high predictive power to infer resistance profiles without the need for time-consuming phenotypic methods.One sentence summaryWhole genome sequencing of clinical M. tuberculosis isolates accurately predicts drug resistance profiles and may replace culture-based drug susceptibility testing in the future.


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