scholarly journals Insights into the genetic diversity ofMycobacterium tuberculosisin Tanzania

2018 ◽  
Author(s):  
Liliana K. Rutaihwa ◽  
Mohamed Sasamalo ◽  
Aladino Jaleco ◽  
Jerry Hella ◽  
Ally Kingazi ◽  
...  
Keyword(s):  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
Clinical Settings ◽  
Nucleotide Polymorphisms ◽  
Related Factors ◽  
Typing Method ◽  
Single Nucleotide ◽  
Lineage 2 ◽  
Phylogenetic Lineages ◽  
Different Strains

AbstractBackgroundHuman tuberculosis (TB) is caused by seven phylogenetic lineages of theMycobacterium tuberculosiscomplex (MTBC), Lineage 1–7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for rapid and phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, different strains of the MTBC influence the outcome of TB infection and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in spite of a high TB burden.Methods and FindingsHere we used a SNP-typing method to genotype a nationwide collection of 2,039 MTBC clinical isolates obtained from new and retreatment TB cases diagnosed in 2012 and 2013. Four lineages, namely Lineage 1–4 were identified. The distribution and frequency of these lineages varied across the regions but overall, Lineage 4 was the most frequent (n=866, 42.5%), followed by Lineage 3 (n=681, 33.4%) and 1 (n=336, 16.5%), with Lineage 2 being the least frequent (n=92, 4.5%). A total of 64 (3.1%) isolates could not be assigned to any lineage. We found Lineage 2 to be associated with female sex (adjusted odds ratio [aOR] 2.25; 95% confidence interval [95% CI] 1.38 – 3.70, p<0.001) and retreatment (aOR 1.78; 95% CI 1.00 – 3.02, p=0.040). We found no associations between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer oligotyping revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected low levels of multidrug resistant isolates among a subset of retreatment casesConclusionsThis study provides novel insights into the influence of pathogen-related factors on the TB epidemic in Tanzania.

scholarly journals A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics

2021 ◽  
Vol 1 ◽  
pp. 100
Author(s):  
Michaela Zwyer ◽  
Cengiz Çavusoglu ◽  
Giovanni Ghielmetti ◽  
Maria Lodovica Pacciarini ◽  
Erika Scaltriti ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Epidemiological Studies ◽  
Nucleotide Polymorphisms ◽  
Phylogenetic Groups ◽  
Single Nucleotide ◽  
Phylogenetic Lineages ◽  
Made In

Background The bacteria that compose the Mycobacterium tuberculosis complex (MTBC) cause tuberculosis (TB) in humans and in different animals, including livestock. Much progress has been made in understanding the population structure of the human-adapted members of the MTBC by combining phylogenetics with genomics. Accompanying the discovery of new genetic diversity, a body of operational nomenclature has evolved to assist comparative and molecular epidemiological studies of human TB. By contrast, for the livestock-associated MTBC members, Mycobacterium bovis, M. caprae and M. orygis, there has been a lack of comprehensive nomenclature to accommodate new genetic diversity uncovered by emerging phylogenomic studies. We propose to fill this gap by putting forward a new nomenclature covering the main phylogenetic groups within M. bovis, M. caprae and M. orygis. Methods We gathered a total of 8,736 whole-genome sequences (WGS) from public sources and 39 newly sequenced strains, and selected a subset of 829 WGS, representative of the worldwide diversity of M. bovis, M. caprae and M. orygis. We used phylogenetics and genetic diversity patterns inferred from WGS to define groups. Results We propose to divide M. bovis, M. caprae and M. orygis in three main phylogenetic lineages, which we named La1, La2 and La3, respectively. Within La1, we identified several monophyletic groups, which we propose to classify into eight sublineages (La1.1-La1.8). These sublineages differed in geographic distribution, with some being geographically restricted and others globally widespread, suggesting different expansion abilities. To ease molecular characterization of these MTBC groups by the community, we provide phylogenetically informed, single nucleotide polymorphisms that can be used as barcodes for genotyping. These markers were implemented in KvarQ and TB-Profiler, which are platform-independent, open-source tools. Conclusions Our results contribute to an improved classification of the genetic diversity within the livestock-associated MTBC, which will benefit future molecular epidemiological and evolutionary studies.

scholarly journals A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics

2021 ◽  
Vol 1 ◽  
pp. 100
Author(s):  
Michaela Zwyer ◽  
Cavusoglu Cengiz ◽  
Giovanni Ghielmetti ◽  
Maria Lodovica Pacciarini ◽  
Erika Scaltriti ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Epidemiological Studies ◽  
Nucleotide Polymorphisms ◽  
Phylogenetic Groups ◽  
Single Nucleotide ◽  
Phylogenetic Lineages ◽  
Test Suit

Background The bacteria that compose the Mycobacterium tuberculosis complex (MTBC) cause tuberculosis (TB) in humans and in different animals, including livestock. Much progress has been made in understanding the population structure of the human-adapted members of the MTBC by combining phylogenetics with genomics. Accompanying the discovery of new genetic diversity, a body of operational nomenclature has evolved to assist comparative and molecular epidemiological studies of human TB. By contrast, for the livestock-associated MTBC members, Mycobacterium bovis, M. caprae and M. orygis, there has been a lack of comprehensive nomenclature to accommodate new genetic diversity uncovered by emerging phylogenomic studies. We propose to fill this gap by putting forward a new nomenclature covering the main phylogenetic groups within M. bovis, M. caprae and M. orygis. Methods We gathered a total of 8,747 whole-genome sequences (WGS) from public sources and 39 newly sequenced strains, and selected a subset of 839 WGS, representative of the worldwide diversity of M. bovis, M. caprae and M. orygis. We used phylogenetics and genetic diversity patterns inferred from WGS to define groups. Results We propose to divide M. bovis, M. caprae and M. orygis, in three main phylogenetic lineages, which we named La1, La2 and La3, respectively. Within La1, we identified several monophyletic groups, which we propose to classify into eight sublineages (La1.1-La1.8). These differed in geographic distribution, with some being geographically restricted and others globally widespread, suggesting different expansion abilities. To ease molecular characterization of these MTBC groups by the community, we provide phylogenetically informed, single nucleotide polymorphisms that can be used as barcodes for genotyping. These makers were implemented in a new test suit in KvarQ, a platform-independent, open-source tool. Conclusions Our results contribute to an improved classification of the genetic diversity within the livestock-associated MTBC, which will benefit future molecular epidemiological and evolutionary studies.

scholarly journals Strain-Specific Genotyping of Bifidobacterium animalis subsp. lactis by Using Single-Nucleotide Polymorphisms, Insertions, and Deletions

2009 ◽  
Vol 75 (23) ◽  
pp. 7501-7508 ◽  
Author(s):  
Elizabeth P. Briczinski ◽  
Joseph R. Loquasto ◽  
Rodolphe Barrangou ◽  
Edward G. Dudley ◽  
Anastasia M. Roberts ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Sequence Similarity ◽  
Nucleotide Polymorphisms ◽  
Strain Specificity ◽  
Typing Method ◽  
Single Nucleotide ◽  
Bifidobacterium Animalis ◽  
Molecular Approaches ◽  
Commercial Applications ◽  
High Level

ABSTRACT Several probiotic strains of Bifidobacterium animalis subsp. lactis are widely supplemented into food products and dietary supplements due to their documented health benefits and ability to survive within the mammalian gastrointestinal tract and acidified dairy products. The strain specificity of these characteristics demands techniques with high discriminatory power to differentiate among strains. However, to date, molecular approaches, such as pulsed-field gel electrophoresis and randomly amplified polymorphic DNA-PCR, have been ineffective at achieving strain separation due to the monomorphic nature of this subspecies. Previously, sequencing and comparison of two B. animalis subsp. lactis genomes (DSMZ 10140 and Bl-04) confirmed this high level of sequence similarity, identifying only 47 single-nucleotide polymorphisms (SNPs) and four insertions and/or deletions (INDELs) between them. In this study, we hypothesized that a sequence-based typing method targeting these loci would permit greater discrimination between strains than previously attempted methods. Sequencing 50 of these loci in 24 strains of B. animalis subsp. lactis revealed that a combination of nine SNPs/INDELs could be used to differentiate strains into 14 distinct genotypic groups. In addition, the presence of a nonsynonymous SNP within the gene encoding a putative glucose uptake protein was found to correlate with the ability of certain strains to transport glucose and to grow rapidly in a medium containing glucose as the sole carbon source. The method reported here can be used in clinical, regulatory, and commercial applications requiring identification of B. animalis subsp. lactis at the strain level.

scholarly journals Can 15-Locus Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Analysis Provide Insight into the Evolution of Mycobacterium tuberculosis?

2005 ◽  
Vol 71 (12) ◽  
pp. 8207-8213 ◽  
Author(s):  
Andrea Gibson ◽  
Timothy Brown ◽  
Lucy Baker ◽  
Francis Drobniewski
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tandem Repeats ◽  
Variable Number Tandem Repeat ◽  
Epidemiological Studies ◽  
Variable Number ◽  
Molecular Techniques ◽  
Nucleotide Polymorphisms ◽  
East African ◽  
Phylogeny And Evolution ◽  
Phylogenetic Lineages

ABSTRACT The phylogeny and evolution of the bacterium Mycobacterium tuberculosis is still poorly understood despite the application of a variety of molecular techniques. We analyzed 469 M. tuberculosis and 49 Mycobacterium bovis isolates to evaluate if the mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR) commonly used for epidemiological studies can define the phylogeny of the M. tuberculosis complex. This population was characterized by previously identified silent single-nucleotide polymorphisms (sSNPs) or by a macroarray based on these sSNPs that was developed in this study. MIRU-VNTR phylogenetic codes capable of differentiating between phylogenetic lineages were identified. Overall, there was 90.9% concordance between the lineages of isolates as defined by the MIRU-VNTR and sSNP analyses. The MIRU-VNTR phylogenetic code was unique to M. bovis and was not observed in any M. tuberculosis isolates. The codes were able to differentiate between different M. tuberculosis strain families such as Beijing, Delhi, and East African-Indian. Discrepant isolates with similar but not identical MIRU-VNTR codes often displayed a stepwise trend suggestive of bidirectional evolution. A lineage-specific panel of MIRU-VNTR can be used to subdivide each lineage for epidemiological purposes. MIRU-VNTR is a valuable tool for phylogenetic studies and could define an evolutionarily uncharacterized population of M. tuberculosis complex organisms.

scholarly journals Whole-genome comparative analysis at the lineage/sublineage level discloses relationships between Mycobacterium tuberculosis genotype and clinical phenotype

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12128
Author(s):  
Andrea Monserrat Negrete-Paz ◽  
Gerardo Vázquez-Marrufo ◽  
Ma. Soledad Vázquez-Garcidueñas
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Clinical Phenotype ◽  
Effective Strain ◽  
Pulmonary Involvement ◽  
Multidrug Resistant ◽  
Nucleotide Polymorphisms ◽  
Mtbc Strain ◽  
Resistant Strains ◽  
Phylogenetic Lineages

Background Human tuberculosis (TB) caused by members of the Mycobacterium tuberculosis complex (MTBC) is the main cause of death among infectious diseases worldwide. Pulmonary TB (PTB) is the most common clinical phenotype of the disease, but some patients develop an extrapulmonary (EPTB) phenotype in which any organ or tissue can be affected. MTBC species include nine phylogenetic lineages, with some appearing globally and others being geographically restricted. EPTB can or not have pulmonary involvement, challenging its diagnosis when lungs are not implicated, thus causing an inadequate treatment. Finding evidence of a specific M. tuberculosis genetic background associated with EPTB is epidemiologically relevant due to the virulent and multidrug-resistant strains isolated from such cases. Until now, the studies conducted to establish associations between M. tuberculosis lineages and PTB/EPTB phenotypes have shown inconsistent results, which are attributed to the strain predominance from specific M. tuberculosis lineages/sublineages in the samples analyzed and the use of low-resolution phylogenetic tools that have impaired sublineage discrimination abilities. The present work elucidates the relationships between the MTBC strain lineages/sublineages and the clinical phenotypes of the disease as well as the antibiotic resistance of the strains. Methods To avoid biases, we retrieved the raw genomic reads (RGRs) of all (n = 245) the M. tuberculosis strains worldwide causing EPTB available in databases and an equally representative sample of the RGRs (n = 245) of PTB strains. A multiple alignment was constructed, and a robust maximum likelihood phylogeny based on single-nucleotide polymorphisms was generated, allowing effective strain lineage/sublineage assignment. Results A significant Odds Ratio (OR range: 1.8–8.1) association was found between EPTB and the 1.1.1, 1.2.1, 4.1.2.1 and ancestral Beijing sublineages. Additionally, a significant association between PTB with 4.3.1, 4.3.3, and 4.5 and Asian African 2 and Europe/Russia B0/W148 modern Beijing sublineages was found. We also observed a significant association of Lineage 3 strains with multidrug resistance (OR 3.8; 95% CI [1.1–13.6]), as well as between modern Beijing sublineages and antibiotic resistance (OR 4.3; 3.8–8.6). In this work, it was found that intralineage diversity can drive differences in the immune response that triggers the PTB/EPTB phenotype.

scholarly journals ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study

2020 ◽  
Author(s):  
Matteo Calcagnile ◽  
Patricia Forgez ◽  
Antonio Iannelli ◽  
Cecilia Bucci ◽  
Marco Alifano ◽  
...  
Keyword(s):  
In Silico ◽  
Alveolar Epithelial Cells ◽  
Nucleotide Polymorphisms ◽  
Related Factors ◽  
Single Nucleotide ◽  
Angiotensin Converting Enzyme 2 ◽  
Alveolar Epithelial ◽  
African People ◽  
In Silico Study ◽  
Ace2 Gene

AbstractThe current SARS covid-19 epidemic spread appears to be influenced by ethnical, geographical and sex-related factors that may involve genetic susceptibility to diseases. Similar to SARS-CoV, SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells, notably type II alveolar epithelial cells. Importantly, ACE2 gene is highly polymorphic. Here we have used in silico tools to analyze the possible impact of ACE2 single-nucleotide polymorphisms (SNPs) on the interaction with SARS-CoV-2 spike glycoprotein. We found that S19P (common in African people) and K26R (common in European people) were, among the most diffused SNPs worldwide, the only two SNPs that were able to potentially affect the interaction of ACE2 with SARS-CoV-2 spike. FireDock simulations demonstrated that while S19P may decrease, K26R might increase the ACE2 affinity for SARS-CoV-2 Spike. This finding suggests that the S19P may genetically protect, and K26R may predispose to more severe SARS-CoV-2 disease.

scholarly journals A Novel 7-Single Nucleotide Polymorphism-Based Clonotyping Test Allows Rapid Prediction of Antimicrobial Susceptibility of Extraintestinal Escherichia coli Directly From Urine Specimens

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Veronika Tchesnokova ◽  
Hovhannes Avagyan ◽  
Mariya Billig ◽  
Sujay Chattopadhyay ◽  
Pavel Aprikian ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Susceptibility ◽  
Clinical Diagnostics ◽  
Resolving Power ◽  
Nucleotide Polymorphisms ◽  
Typing Method ◽  
Single Nucleotide ◽  
E Coli ◽  
Specificity And Sensitivity ◽  
Urine Specimens

Abstract Background.  Escherichia coli is a highly clonal pathogen. Extraintestinal isolates belong to a limited number of genetically related groups, which often exhibit characteristic antimicrobial resistance profiles. Methods.  We developed a rapid clonotyping method for extraintestinal E coli based on detection of the presence or absence of 7 single nucleotide polymorphisms (SNPs) within 2 genes (fumC and fimH). A reference set of 2559 E coli isolates, primarily of urinary origin, was used to predict the resolving power of the 7-SNP-based typing method, and 582 representative strains from this set were used to evaluate test robustness. Results.  Fifty-four unique SNP combinations (“septatypes”) were identified in the reference strains. These septatypes yielded a clonal group resolution power on par with that of traditional multilocus sequence typing. In 72% of isolates, septatype identity predicted sequence type identity with at least 90% (mean, 97%) accuracy. Most septatypes exhibited highly distinctive antimicrobial susceptibility profiles. The 7-SNP-based test could be performed with high specificity and sensitivity using single or multiplex conventional polymerase chain reaction (PCR) and quantitative PCR. In the latter format, E coli presence and septatype identity were determined directly in urine specimens within 45 minutes with bacterial loads as low as 102 colony-forming units/mL and, at clinically significant bacterial loads, with 100% sensitivity and specificity. Conclusions.  7-SNP-based typing of E coli can be used for both epidemiological studies and clinical diagnostics, which could greatly improve the empirical selection of antimicrobial therapy.

scholarly journals Genotypic analyses of uropathogenic Escherichia coli based on fimH single nucleotide polymorphisms (SNPs)

2007 ◽  
Vol 56 (10) ◽  
pp. 1363-1369 ◽  
Author(s):  
Sara Y. Tartof ◽  
Owen D. Solberg ◽  
Lee W. Riley
Keyword(s):  
Escherichia Coli ◽  
Single Nucleotide Polymorphisms ◽  
Screening Test ◽  
Epidemiological Studies ◽  
Discriminatory Power ◽  
Snp Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Discriminatory Ability ◽  
E Coli

The application of genotyping techniques for subtyping uropathogenic Escherichia coli has contributed to better understanding of the epidemiology of community-acquired urinary tract infection (UTI). However, the current techniques are hampered by limited reproducibility, poor discriminatory power, labour-intensive performance or high cost. A screening test that is sequence-based would provide an inexpensive, reproducible way to subtype E. coli isolates. Such a test, if also discriminatory, would be highly useful for epidemiological studies. The discriminatory ability of 12 putative virulence genes (fimH, fliD, fliM, iha, motA, papA/H, kpsMTII, fepE, fimA, flgA, malG, purD) was evaluated based on single nucleotide polymorphisms (SNPs) in nine uropathogenic E. coli isolates, all previously found to belong to a single multilocus sequence type (MLST) complex (ST69). An additional 25 epidemiologically well-characterized E. coli isolates belonging to 12 distinct MLST clonal complexes were analysed for fimH SNP. None of the 12 genes except fimH were able to further discriminate the nine ST69-complex strains. Isolates belonging to the 12 non-ST69 MLST groups were separated into 10 fimH SNP subgroups. While fimH SNP analysis may not be an appropriate phylogenetic method, it offers discriminatory power similar to that of MLST and could be used as a simple, inexpensive screening test for epidemiological studies of uropathogenic E. coli.

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