scholarly journals Single-Nucleotide Polymorphism-Based Genetic Diversity Analysis of Clinical Pseudomonas aeruginosa Isolates

2020 ◽  
Vol 12 (4) ◽  
pp. 396-406 ◽  
Author(s):  
Uthayakumar Muthukumarasamy ◽  
Matthias Preusse ◽  
Adrian Kordes ◽  
Michal Koska ◽  
Monika Schniederjans ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Single Nucleotide Polymorphisms ◽  
Core Genome ◽  
Phenotypic Diversity ◽  
Bacterial Species ◽  
Genomic Variation ◽  
Genomic Diversity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Changes

Abstract Extensive use of next-generation sequencing has the potential to transform our knowledge on how genomic variation within bacterial species impacts phenotypic versatility. Because different environments have unique selection pressures, they drive divergent evolution. However, there is also parallel or convergent evolution of traits in independent bacterial isolates inhabiting similar environments. The application of tools to describe population-wide genomic diversity provides an opportunity to measure the predictability of genetic changes underlying adaptation. Here, we describe patterns of sequence variations in the core genome among 99 individual Pseudomonas aeruginosa clinical isolates and identified single-nucleotide polymorphisms that are the basis for branching of the phylogenetic tree. We also identified single-nucleotide polymorphisms that were acquired independently, in separate lineages, and not through inheritance from a common ancestor. Although our results demonstrate that the Pseudomonas aeruginosa core genome is highly conserved and in general, not subject to adaptive evolution, instances of parallel evolution will provide an opportunity to uncover genetic changes that underlie phenotypic diversity.

scholarly journals Genomic surveillance of COVID-19 cases in Beijing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Pengcheng Du ◽  
Nan Ding ◽  
Jiarui Li ◽  
Fujie Zhang ◽  
Qi Wang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
High Frequency ◽  
Epidemiological Data ◽  
Genomic Diversity ◽  
Nucleotide Polymorphisms ◽  
Genomic Evolution ◽  
Single Nucleotide ◽  
Imported Cases ◽  
Single Nucleotide Variations ◽  
Local Transmission

Abstract The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.

scholarly journals Complete Genome Sequence of Yersinia pestis Strains Antiqua and Nepal516: Evidence of Gene Reduction in an Emerging Pathogen

2006 ◽  
Vol 188 (12) ◽  
pp. 4453-4463 ◽  
Author(s):  
Patrick S. G. Chain ◽  
Ping Hu ◽  
Stephanie A. Malfatti ◽  
Lyndsay Radnedge ◽  
Frank Larimer ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Yersinia Pestis ◽  
Yersinia Pseudotuberculosis ◽  
Open Reading Frames ◽  
Genomic Diversity ◽  
Avirulent Strain ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Protein Coding ◽  
Definition Of

ABSTRACT Yersinia pestis, the causative agent of bubonic and pneumonic plagues, has undergone detailed study at the molecular level. To further investigate the genomic diversity among this group and to help characterize lineages of the plague organism that have no sequenced members, we present here the genomes of two isolates of the “classical” antiqua biovar, strains Antiqua and Nepal516. The genomes of Antiqua and Nepal516 are 4.7 Mb and 4.5 Mb and encode 4,138 and 3,956 open reading frames, respectively. Though both strains belong to one of the three classical biovars, they represent separate lineages defined by recent phylogenetic studies. We compare all five currently sequenced Y. pestis genomes and the corresponding features in Yersinia pseudotuberculosis. There are strain-specific rearrangements, insertions, deletions, single nucleotide polymorphisms, and a unique distribution of insertion sequences. We found 453 single nucleotide polymorphisms in protein-coding regions, which were used to assess the evolutionary relationships of these Y. pestis strains. Gene reduction analysis revealed that the gene deletion processes are under selective pressure, and many of the inactivations are probably related to the organism's interaction with its host environment. The results presented here clearly demonstrate the differences between the two biovar antiqua lineages and support the notion that grouping Y. pestis strains based strictly on the classical definition of biovars (predicated upon two biochemical assays) does not accurately reflect the phylogenetic relationships within this species. A comparison of four virulent Y. pestis strains with the human-avirulent strain 91001 provides further insight into the genetic basis of virulence to humans.

scholarly journals Transposable elements are important contributors to standing variation in gene expression in Capsella grandiflora

2018 ◽  
Author(s):  
Jasmina Uzunović ◽  
Emily B. Josephs ◽  
John R. Stinchcombe ◽  
Stephen I. Wright
Keyword(s):  
Gene Expression ◽  
Single Nucleotide Polymorphisms ◽  
Transposable Elements ◽  
Genomic Diversity ◽  
Nucleotide Polymorphisms ◽  
Mobile Dna ◽  
Gene Expression Variation ◽  
Single Nucleotide ◽  
Expression Variation ◽  
A Genome

AbstractTransposable elements (TEs) make up a significant portion of eukaryotic genomes, and thus are important drivers of genome evolution. However, the evolutionary forces controlling TE copy number and the extent to which TEs affect phenotypic variation on a genome-wide scale are still unclear. We characterised TE insertion polymorphism and its effects on gene expression in 124 whole genome sequences from a single population of Capsella grandiflora. The frequency of insertions was negatively correlated with distance to genes, as well as density of conserved non-coding elements, suggesting that the negative effects of TEs on gene regulation are important in limiting their abundance. Rare TE variants strongly influence gene expression variation, predominantly through downregulation. In contrast, rare single nucleotide polymorphisms (SNPs) contribute equally to up- and down-regulation, but have a weaker effect. Taken together, these results imply that TEs are a significant contributor to gene expression variation and can be more likely than rare SNPs to cause extreme changes in gene expression.Author SummaryTransposable elements (TEs), mobile DNA elements with the ability to excise from the genome and reinsert in new locations, are important components of genomic diversity. Due to their abundance and mobility, TEs play an influential role in genomic evolution, often deleterious. Here we show that TEs in a population of the plant Capsella grandiflora are most deleterious when they insert in genic and regulatory regions. We find that TEs indeed are associated with unusual levels of gene expression, predominantly decreased expression.Furthermore, this effect is stronger than the association of single nucleotide polymorphisms with gene expression variation, highlighting the importance of TE contribution to the maintenance of expression variation.

scholarly journals Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pornpen Tantivitayakul ◽  
Wuthiwat Ruangchai ◽  
Tada Juthayothin ◽  
Nat Smittipat ◽  
Areeya Disratthakit ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Nucleotide Polymorphisms ◽  
Phenotypic Diversity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Comparative genome analysis of a multidrug-resistant Pseudomonas aeruginosa sequence type 277 clone that harbours two copies of the blaSPM-1 gene and multiple single nucleotide polymorphisms in other resistance-associated genes

2019 ◽  
Author(s):  
Ana Paula Barbosa do Nascimento ◽  
Fernando Medeiros Filho ◽  
Hério Sousa ◽  
Hermes Senger ◽  
Rodolpho Mattos Albano ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Single Nucleotide Polymorphisms ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Genomic Islands ◽  
Genome Comparison ◽  
Nucleotide Polymorphisms ◽  
Emerging Pathogens ◽  
Single Nucleotide

AbstractPseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of blaSPM-1 gene, encoding a metallo-beta-lactamase, in addition to other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify physiological key aspects that may lead to the exposure of new targets for therapy. This study was designed to characterize the genome of Pseudomonas aeruginosa CCBH4851 through the detection of genomic features and genome comparison with other Pseudomonas aeruginosa strains. The CCBH4851 closed genome showed features that were consistent with data reported for the specie. However, comparative genomics revealed the absence of genes important for pathogenesis. On the other hand, CCBH4851 genome contained acquired genomic islands that carry additional virulence and antimicrobial resistance-related genes. The presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations could influence the multidrug-resistant behavior of CCBH4851. Overall, the characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed several features that could directly impact the profile of virulence and antibiotic resistance of this pathogen in infectious outbreaks.

scholarly journals Imidazopyridine Compounds Inhibit Mycobacterial Growth by Depleting ATP Levels

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Theresa O'Malley ◽  
Torey Alling ◽  
Julie V. Early ◽  
Heather A. Wescott ◽  
Anuradha Kumar ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Bacterial Species ◽  
Cross Resistance ◽  
Nucleotide Polymorphisms ◽  
Ph Homeostasis ◽  
Single Nucleotide ◽  
Atp Generation ◽  
Resistant Mutants

ABSTRACT The imidazopyridines are a promising new class of antitubercular agents with potent activity in vitro and in vivo . We isolated mutants of Mycobacterium tuberculosis resistant to a representative imidazopyridine; the mutants had large shifts (>20-fold) in MIC. Whole-genome sequencing revealed mutations in Rv1339, a hypothetical protein of unknown function. We isolated mutants resistant to three further compounds from the series; resistant mutants isolated from two of the compounds had single nucleotide polymorphisms in Rv1339 and resistant mutants isolated from the third compound had single nucleotide polymorphisms in QcrB, the proposed target for the series. All the strains were resistant to two compounds, regardless of the mutation, and a strain carrying the QcrB T313I mutation was resistant to all of the imidazopyridine derivatives tested, confirming cross-resistance. By monitoring pH homeostasis and ATP generation, we confirmed that compounds from the series were targeting QcrB; imidazopyridines disrupted pH homeostasis and depleted ATP, providing further evidence of an effect on the electron transport chain. A representative compound was bacteriostatic against replicating bacteria, consistent with a mode of action against QcrB. The series had a narrow inhibitory spectrum, with no activity against other bacterial species. No synergy or antagonism was seen with other antituberculosis drugs under development. In conclusion, our data support the hypothesis that the imidazopyridine series functions by reducing ATP generation via inhibition of QcrB.

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