scholarly journals Comparative Analysis of Whole-Genome and Methylome Profiles of a Smooth and a Rough Mycobacterium abscessus Clinical Strain

2019 ◽  
Vol 10 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Chiranjibi Chhotaray ◽  
Shuai Wang ◽  
Yaoju Tan ◽  
Amjad Ali ◽  
Muhammad Shehroz ◽  
...  
Keyword(s):  
Single Molecule ◽  
Gene Clusters ◽  
Mycobacterium Abscessus ◽  
Clinical Strain ◽  
Comparative Genomic ◽  
Illumina Hiseq ◽  
Clinical Strains ◽  
Synonymous Mutations ◽  
Pan Genome ◽  
Genome Wide

Mycobacterium abscessus is a fast growing Mycobacterium species mainly causing skin and respiratory infections in human. M. abscessus is resistant to numerous drugs, which is a major challenge for the treatment. In this study, we have sequenced the genomes of two clinical M. abscessus strains having rough and smooth morphology, using the single molecule real-time and Illumina HiSeq sequencing technology. In addition, we reported the first comparative methylome profiles of a rough and a smooth M. abscessus clinical strains. The number of N4-methylcytosine (4mC) and N6-methyladenine (6mA) modified bases obtained from smooth phenotype were two-fold and 1.6 fold respectively higher than that of rough phenotype. We have also identified 4 distinct novel motifs in two clinical strains and genes encoding antibiotic-modifying/targeting enzymes and genes associated with intracellular survivability having different methylation patterns. To our knowledge, this is the first report about genome-wide methylation profiles of M. abscessus strains and identification of a natural linear plasmid (15 kb) in this critical pathogen harboring methylated bases. The pan-genome analysis of 25 M. abscessus strains including two clinical strains revealed an open pan genome comprises of 7596 gene clusters. Likewise, structural variation analysis revealed that the genome of rough phenotype strain contains more insertions and deletions than the smooth phenotype and that of the reference strain. A total of 391 single nucleotide variations responsible for the non-synonymous mutations were detected in clinical strains compared to the reference genome. The comparative genomic analysis elucidates the genome plasticity in this emerging pathogen. Furthermore, the detection of genome-wide methylation profiles of M. abscessus clinical strains may provide insight into the significant role of DNA methylation in pathogenicity and drug resistance in this opportunistic pathogen.

scholarly journals Genomic Characteristics and Comparative Genomics Analysis of Two Chinese Corynespora cassiicola Strains Causing Corynespora Leaf Fall (CLF) Disease

2021 ◽  
Vol 7 (6) ◽  
pp. 485
Author(s):  
Boxun Li ◽  
Yang Yang ◽  
Jimiao Cai ◽  
Xianbao Liu ◽  
Tao Shi ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Single Molecule ◽  
Rubber Tree ◽  
Gene Families ◽  
Gene Clusters ◽  
The Philippines ◽  
Tree Plantations ◽  
Comparative Genomic ◽  
Corynespora Cassiicola ◽  
Leaf Fall

Rubber tree Corynespora leaf fall (CLF) disease, caused by the fungus Corynespora cassiicola, is one of the most damaging diseases in rubber tree plantations in Asia and Africa, and this disease also threatens rubber nurseries and young rubber plantations in China. C. cassiicola isolates display high genetic diversity, and virulence profiles vary significantly depending on cultivar. Although one phytotoxin (cassicolin) has been identified, it cannot fully explain the diversity in pathogenicity between C. cassiicola species, and some virulent C. cassiicola strains do not contain the cassiicolin gene. In the present study, we report high-quality gapless genome sequences, obtained using short-read sequencing and single-molecule long-read sequencing, of two Chinese C. cassiicola virulent strains. Comparative genomics of gene families in these two stains and a virulent CPP strain from the Philippines showed that all three strains experienced different selective pressures, and metabolism-related gene families vary between the strains. Secreted protein analysis indicated that the quantities of secreted cell wall-degrading enzymes were correlated with pathogenesis, and the most aggressive CCP strain (cassiicolin toxin type 1) encoded 27.34% and 39.74% more secreted carbohydrate-active enzymes (CAZymes) than Chinese strains YN49 and CC01, respectively, both of which can only infect rubber tree saplings. The results of antiSMASH analysis showed that all three strains encode ~60 secondary metabolite biosynthesis gene clusters (SM BGCs). Phylogenomic and domain structure analyses of core synthesis genes, together with synteny analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters, revealed diversity in the distribution of SM BGCs between strains, as well as SM polymorphisms, which may play an important role in pathogenic progress. The results expand our understanding of the C. cassiicola genome. Further comparative genomic analysis indicates that secreted CAZymes and SMs may influence pathogenicity in rubber tree plantations. The findings facilitate future exploration of the molecular pathogenic mechanism of C. cassiicola.

scholarly journals Mutations in dnaA and a cryptic interaction site increase drug resistance in Mycobacterium tuberculosis

2020 ◽  
Vol 16 (11) ◽  
pp. e1009063
Author(s):  
Nathan D. Hicks ◽  
Samantha R. Giffen ◽  
Peter H. Culviner ◽  
Michael C. Chao ◽  
Charles L. Dulberger ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genome Wide Association Study ◽  
Critical Concentration ◽  
Drug Susceptibility ◽  
Interaction Site ◽  
Clinical Strains ◽  
Synonymous Mutations ◽  
Genome Wide ◽  
A Genome

Genomic dissection of antibiotic resistance in bacterial pathogens has largely focused on genetic changes conferring growth above a single critical concentration of drug. However, reduced susceptibility to antibiotics—even below this breakpoint—is associated with poor treatment outcomes in the clinic, including in tuberculosis. Clinical strains of Mycobacterium tuberculosis exhibit extensive quantitative variation in antibiotic susceptibility but the genetic basis behind this spectrum of drug susceptibility remains ill-defined. Through a genome wide association study, we show that non-synonymous mutations in dnaA, which encodes an essential and highly conserved regulator of DNA replication, are associated with drug resistance in clinical M. tuberculosis strains. We demonstrate that these dnaA mutations specifically enhance M. tuberculosis survival during isoniazid treatment via reduced expression of katG, the activator of isoniazid. To identify DnaA interactors relevant to this phenotype, we perform the first genome-wide biochemical mapping of DnaA binding sites in mycobacteria which reveals a DnaA interaction site that is the target of recurrent mutation in clinical strains. Reconstructing clinically prevalent mutations in this DnaA interaction site reproduces the phenotypes of dnaA mutants, suggesting that clinical strains of M. tuberculosis have evolved mutations in a previously uncharacterized DnaA pathway that quantitatively increases resistance to the key first-line antibiotic isoniazid. Discovering genetic mechanisms that reduce drug susceptibility and support the evolution of high-level drug resistance will guide development of biomarkers capable of prospectively identifying patients at risk of treatment failure in the clinic.

scholarly journals How to make a rodent giant: Genomic basis and tradeoffs of gigantism in the capybara, the world’s largest rodent

2020 ◽  
Author(s):  
Santiago Herrera-Álvarez ◽  
Elinor Karlsson ◽  
Oliver A Ryder ◽  
Kerstin Lindblad-Toh ◽  
Andrew J Crawford
Keyword(s):  
Body Size ◽  
Draft Genome ◽  
Large Body ◽  
Comparative Genomic ◽  
Specific Gene ◽  
Large Body Size ◽  
Synonymous Mutations ◽  
Intragenomic Conflict ◽  
Genome Wide ◽  
A Genome

Abstract Gigantism results when one lineage within a clade evolves extremely large body size relative to its small-bodied ancestors, a common phenomenon in animals. Theory predicts that the evolution of giants should be constrained by two tradeoffs. First, because body size is negatively correlated with population size, purifying selection is expected to be less efficient in species of large body size, leading to increased mutational load. Second, gigantism is achieved through generating a higher number of cells along with higher rates of cell proliferation, thus increasing the likelihood of cancer. To explore the genetic basis of gigantism in rodents and uncover genomic signatures of gigantism-related tradeoffs, we assembled a draft genome of the capybara (Hydrochoerus hydrochaeris), the world’s largest living rodent. We found that the genome-wide ratio of non-synonymous to synonymous mutations (ω) is elevated in the capybara relative to other rodents, likely caused by a generation-time effect and consistent with a nearly-neutral model of molecular evolution. A genome-wide scan for adaptive protein evolution in the capybara highlighted several genes controlling post-natal bone growth regulation and musculoskeletal development, which are relevant to anatomical and developmental modifications for an increase in overall body size. Capybara-specific gene-family expansions included a putative novel anticancer adaptation that involves T cell-mediated tumor suppression, offering a potential resolution to the increased cancer risk in this lineage. Our comparative genomic results uncovered the signature of an intragenomic conflict where the evolution of gigantism in the capybara involved selection on genes and pathways that are directly linked to cancer.

scholarly journals A Genomic Virulence Reference Map of Enterococcus faecalis Reveals an Important Contribution of Phage03-Like Elements in Nosocomial Genetic Lineages to Pathogenicity in a Caenorhabditis elegans Infection Model

2015 ◽  
Vol 83 (5) ◽  
pp. 2156-2167 ◽  
Author(s):  
Sabina Leanti La Rosa ◽  
Lars-Gustav Snipen ◽  
Barbara E. Murray ◽  
Rob J. L. Willems ◽  
Michael S. Gilmore ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Enterococcus Faecalis ◽  
Principal Component ◽  
Gene Clusters ◽  
Clinical Strain ◽  
Comparative Genomic ◽  
Infection Model ◽  
Content Type ◽  
C Elegans ◽  
Virulence Traits

In the present study, the commensal and pathogenic host-microbe interaction ofEnterococcus faecaliswas explored using aCaenorhabditis elegansmodel system. The virulence of 28E. faecalisisolates representing 24 multilocus sequence types (MLSTs), including human commensal and clinical isolates as well as isolates from animals and of insect origin, was investigated usingC. elegansstrainglp-4(bn2ts);sek-1(km4). This revealed that 6E. faecalisisolates behaved in a commensal manner with no nematocidal effect, while the remaining strains showed a time to 50% lethality ranging from 47 to 120 h. Principal component analysis showed that the difference in nematocidal activity explained 94% of the variance in the data. Assessment of known virulence traits revealed that gelatinase and cytolysin production accounted for 40.8% and 36.5% of the observed pathogenicity, respectively. However, coproduction of gelatinase and cytolysin did not increase virulence additively, accounting for 50.6% of the pathogenicity and therefore indicating a significant (26.7%) saturation effect. We employed a comparative genomic analysis approach using the 28 isolates comprising a collection of 82,356 annotated coding sequences (CDS) to identify 2,325 patterns of presence or absence among the investigated strains. Univariate statistical analysis of variance (ANOVA) established that individual patterns positively correlated (n= 61) with virulence. The patterns were investigated to identify potential new virulence traits, among which we found five patterns consisting of the phage03-like gene clusters. Strains harboring phage03 showed, on average, 17% higher killing ofC. elegans(P= 4.4e−6). The phage03 gene cluster was also present in gelatinase-and-cytolysin-negative strainE. faecalisJH2-2. Deletion of this phage element from the JH2-2 clinical strain rendered the mutant apathogenic inC. elegans, and a similar mutant of the nosocomial V583 isolate showed significantly attenuated virulence. Bioinformatics investigation indicated that, unlike otherE. faecalisvirulence traits, phage03-like elements were found at a higher frequency among nosocomial isolates. In conclusion, our report provides a valuable virulence map that explains enhancement inE. faecalisvirulence and contributes to a deeper comprehension of the genetic mechanism leading to the transition from commensalism to a pathogenic lifestyle.

scholarly journals Genome-Wide Analysis of Four Pathotypes of Wheat Rust Pathogen (Puccinia graminis) Reveals Structural Variations and Diversifying Selection

2021 ◽  
Vol 7 (9) ◽  
pp. 701
Author(s):  
Kanti Kiran ◽  
Hukam C. Rawal ◽  
Himanshu Dubey ◽  
Rajdeep Jaswal ◽  
Subhash C. Bhardwaj ◽  
...  
Keyword(s):  
Control Measures ◽  
Comparative Genomic ◽  
Puccinia Graminis ◽  
Structural Variations ◽  
Illumina Hiseq ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Genomic Studies ◽  
Paired End Sequencing ◽  
Wheat Rust

Diseases caused by Puccinia graminis are some of the most devastating diseases of wheat. Extensive genomic understanding of the pathogen has proven helpful not only in understanding host- pathogen interaction but also in finding appropriate control measures. In the present study, whole-genome sequencing of four diverse P. graminis pathotypes was performed to understand the genetic variation and evolution. An average of 63.5 Gb of data per pathotype with about 100× average genomic coverage was achieved with 100-base paired-end sequencing performed with Illumina Hiseq 1000. Genome structural annotations collectively predicted 9273 functional proteins including ~583 extracellular secreted proteins. Approximately 7.4% of the genes showed similarity with the PHI database which is suggestive of their significance in pathogenesis. Genome-wide analysis demonstrated pathotype 117-6 as likely distinct and descended through a different lineage. The 3–6% more SNPs in the regulatory regions and 154 genes under positive selection with their orthologs and under negative selection in the other three pathotypes further supported pathotype 117-6 to be highly diverse in nature. The genomic information generated in the present study could serve as an important source for comparative genomic studies across the genus Puccinia and lead to better rust management in wheat.

scholarly journals Whole-Genome Sequencing of Corallococcus sp. Strain EGB Reveals the Genetic Determinants Linking Taxonomy and Predatory Behavior

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1421
Author(s):  
Yuqiang Zhao ◽  
Yanxin Wang ◽  
Chengyao Xia ◽  
Xu Li ◽  
Xianfeng Ye ◽  
...  
Keyword(s):  
Extracellular Enzymes ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Predatory Behavior ◽  
Phytopathogenic Fungi ◽  
Plant Diseases ◽  
Comparative Genomic ◽  
Comprehensive Overview ◽  
Circular Chromosome ◽  
Pan Genome

Corallococcus sp. strain EGB is a Gram-negative myxobacteria isolated from saline soil, and has considerable potential for the biocontrol of phytopathogenic fungi. However, the detailed mechanisms related to development and predatory behavior are unclear. To obtain a comprehensive overview of genetic features, the genome of strain EGB was sequenced, annotated, and compared with 10 other Corallococcus species. The strain EGB genome was assembled as a single circular chromosome of 9.4 Mb with 7916 coding genes. Phylogenomics analysis showed that strain EGB was most closely related to Corallococcus interemptor AB047A, and it was inferred to be a novel species within the Corallococcus genus. Comparative genomic analysis revealed that the pan-genome of Corallococcus genus was large and open. Only a small proportion of genes were specific to strain EGB, and most of them were annotated as hypothetical proteins. Subsequent analyses showed that strain EGB produced abundant extracellular enzymes such as chitinases and β-(1,3)-glucanases, and proteases to degrade the cell-wall components of phytopathogenic fungi. In addition, 35 biosynthetic gene clusters potentially coding for antimicrobial compounds were identified in the strain EGB, and the majority of them were present in the dispensable pan-genome with unexplored metabolites. Other genes related to secretion and regulation were also explored for strain EGB. This study opens new perspectives in the greater understanding of the predatory behavior of strain EGB, and facilitates a potential application in the biocontrol of fungal plant diseases in the future.

scholarly journals Comparative genomic analysis of Mycobacterium tuberculosis reveals evolution and genomic instability within Uganda I sub-lineage

2020 ◽  
Author(s):  
Stephen Kanyerezi ◽  
Patricia Nabisubi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Core Genome ◽  
Variant Calling ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Genome Wide Association ◽  
Comparative Genomic ◽  
Pan Genome ◽  
Genome Wide

AbstractIntroductionTuberculosis (TB) is the leading cause of morbidity and mortality globally, responsible for an estimated annual 10.0 million new cases and 1.3 million deaths among infectious diseases with Africa contributing a quarter of these cases in 2019. Classification of Mycobacterium tuberculosis (MTB) strains is important in understanding their geographical predominance and pathogenicity. Different studies have gone ahead to classify MTB using different methods. Some of these include; RFLP, spoligotyping, MIRU-VNTR and SNP set based phylogeny. The SNP set based classification has been found to be in concordance with the region of difference (RD) analysis of MTB complex classification system. In Uganda, the most common cause of pulmonary tuberculosis (PTB) is Uganda genotype of MTB and accounts for up to 70 % of isolates.MethodsSequenced MTB genome samples were retrieved from NCBI and others from local sequencing projects. The genomes were subjected to snippy (a rapid haploid variant calling and core genome alignment) to call variants and annotate them. Outputs from snippy were used to classify the isolates into Uganda genotypes and Non Ugandan genotypes based on 62 SNP set. The Ugandan genotype isolates were later subjected to 413 SNP set and then to a pan genome wide association analysis.Results6 Uganda genotype isolates were found not to classify as either Uganda I or II genotypes based on the 62 SNP set. Using the 413 SNP set, the 6 Uganda genotype isolates were found to have only one SNP out of the 7 SNPs that classify the Uganda I genotypes. They were also found to have both missense and frameshift mutations within the ctpH gene whereas the rest of Uganda I that had a mutation within this gene, was a missense.ConclusionAmong the Uganda genotypes genomes, Uganda I genomes are unstable. We used publicly available datasets to perform analysis like mapping, variant calling, mixed infection, pan-genome analysis to investigate and compare evolution of the Ugandan genotype.

scholarly journals Detection and Assessment of Clarithromycin Inducible Resistant Strains Among Korean Mycobacterium abscessus Clinical Strains: PCR Methods

2014 ◽  
Vol 28 (5) ◽  
pp. 409-414 ◽  
Author(s):  
Seung‐Heon Lee ◽  
Hee Kyung Yoo ◽  
Seol Hee Kim ◽  
Won‐Jung Koh ◽  
Chang Ki Kim ◽  
...  
Keyword(s):  
Mycobacterium Abscessus ◽  
Clinical Strains ◽  
Resistant Strains

scholarly journals Categorization of Orthologous Gene Clusters in 92 Ascomycota Genomes Reveals Functions Important for Phytopathogenicity

2021 ◽  
Vol 7 (5) ◽  
pp. 337
Author(s):  
Daniel Peterson ◽  
Tang Li ◽  
Ana M. Calvo ◽  
Yanbin Yin
Keyword(s):  
Comparative Genomics ◽  
Orthologous Gene ◽  
Gene Clusters ◽  
Phytopathogenic Fungi ◽  
Secreted Proteins ◽  
Economic Losses ◽  
Comparative Genomic ◽  
Signal Peptides ◽  
Comparative Genomics Analysis

Phytopathogenic Ascomycota are responsible for substantial economic losses each year, destroying valuable crops. The present study aims to provide new insights into phytopathogenicity in Ascomycota from a comparative genomic perspective. This has been achieved by categorizing orthologous gene groups (orthogroups) from 68 phytopathogenic and 24 non-phytopathogenic Ascomycota genomes into three classes: Core, (pathogen or non-pathogen) group-specific, and genome-specific accessory orthogroups. We found that (i) ~20% orthogroups are group-specific and accessory in the 92 Ascomycota genomes, (ii) phytopathogenicity is not phylogenetically determined, (iii) group-specific orthogroups have more enriched functional terms than accessory orthogroups and this trend is particularly evident in phytopathogenic fungi, (iv) secreted proteins with signal peptides and horizontal gene transfers (HGTs) are the two functional terms that show the highest occurrence and significance in group-specific orthogroups, (v) a number of other functional terms are also identified to have higher significance and occurrence in group-specific orthogroups. Overall, our comparative genomics analysis determined positive enrichment existing between orthogroup classes and revealed a prediction of what genomic characteristics make an Ascomycete phytopathogenic. We conclude that genes shared by multiple phytopathogenic genomes are more important for phytopathogenicity than those that are unique in each genome.

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