scholarly journals Combined Pan-, Population-, and Phylo-Genomic Analysis of Aspergillus fumigatus Reveals Population Structure and Lineage-Specific Diversity

2021 ◽  
Author(s):  
Lotus A Lofgren ◽  
Brandon S Ross ◽  
Robert A Cramer ◽  
Jason Eric Stajich
Keyword(s):  
Population Structure ◽  
Aspergillus Fumigatus ◽  
Intraspecific Variation ◽  
Resistance Genes ◽  
Reference Genome ◽  
Antifungal Resistance ◽  
Functional Enrichment ◽  
Promising Alternative ◽  
Accessory Genes ◽  
Genomic Analyses

Aspergillus fumigatus is a deadly agent of human fungal disease, where virulence heterogeneity is thought to be at least partially structured by genetic variation between strains. While population genomic analyses based on reference genome alignments offer valuable insights into how gene variants are distributed across populations, these approaches fail to capture intraspecific variation in genes absent from the reference genome. Pan-genomic analyses based on de novo assemblies offer a promising alternative to reference-based genomics, with the potential to address the full genetic repertoire of a species. Here, we use a combination of population genomics, phylogenomics, and pan-genomics to assess population structure and recombination frequency, phylogenetically structured gene presence-absence variation, evidence for metabolic specificity, and the distribution of putative antifungal resistance genes in A. fumigatus. We provide evidence for three distinct populations of A. fumigatus, structured by both gene variation (SNPs and indels) and distinct gene presence-absence variation with unique suites of accessory genes present exclusively in each clade. Accessory genes displayed functional enrichment for nitrogen and carbohydrate metabolism, hinting that populations may be stratified by environmental niche specialization. Similarly, the distribution of antifungal resistance genes and resistance alleles were often structured by phylogeny. Despite low levels of outcrossing, A. fumigatus demonstrated a large pan-genome including many genes unrepresented in the Af293 reference genome. These results highlight the inadequacy of relying on a single-reference genome based approach for evaluating intraspecific variation, and the power of combined genomic approaches to elucidate population structure, genetic diversity, and putative ecological drivers of clinically relevant fungi.

scholarly journals Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

2018 ◽  
Author(s):  
Chrispin Chaguza ◽  
Ellen Heinsbroek ◽  
Rebecca A. Gladstone ◽  
Terence Tafatatha ◽  
Maaike Alaerts ◽  
...  
Keyword(s):  
Population Structure ◽  
Mobile Genetic Elements ◽  
Post Vaccination ◽  
Accessory Genome ◽  
Genetic Elements ◽  
Genomic Level ◽  
Accessory Genes ◽  
Serotype Replacement ◽  
Vaccine Type ◽  
Genome Level

AbstractPneumococcal conjugate vaccines (PCV) have reduced pneumococcal diseases globally. Despite this, much remains to be learned about their effect on pathogen population structure. Here we undertook whole genome sequencing of 660 pneumococcal strains from asymptomatic carriers to investigate population restructuring in pneumococcal strains sampled before and after PCV13 introduction in a previously vaccine-naïve setting. We show substantial decreasing frequency of vaccine-type (VT) strains and their strain diversity post-vaccination in the vaccinated but not unvaccinated age groups indicative of direct but limited or delayed indirect effect of vaccination. Clearance of identical VT serotypes associated with multiple lineages occurred regardless of their genetic background. Interestingly, despite the increasing frequency of non-vaccine type (NVT) strains through serotype replacement, the serotype diversity was not fully restored to the levels observed prior to vaccination implying limited serotype replacement. The frequency of antibiotic resistant strains was low and remained largely unchanged post-vaccination but intermediate-penicillin-resistant lineages were reduced in the post vaccine population. Significant perturbations marked by changing frequency of accessory genes associated with diverse functions especially mobile genetic elements and bacteriocin activity were detected. This phylogenomic analysis demonstrates early vaccine-induced pneumococcal population restructuring not only at serotype but also accessory genome level.Author summaryDifferent formulations of PCVs have been effective in reducing the invasive pneumococcal disease burden globally. Clinical trials have started to indicate high impact and effectiveness of PCV13 in Sub Saharan Africa (SSA) but there is limited understanding of how the introduction of PCVs alters the population structure of pneumococcal strains at serotype and genomic level. Here we investigated this using pneumococcal strains sampled pre‐ and post-PCV13 introduction from a previously vaccine naïve setting in Northern Malawi. Our findings reveal decrease in frequency of VT serotypes and their associated lineages in the largely vaccinated under-five population but not older individuals indicating a direct but limited or delayed indirect protection. The diversity of serotypes also decreased post-vaccination in VT strains in the under-fives but there was no change in NVT strains suggesting incomplete serotype replacement. At the genomic level, logistic regression revealed changing frequency of accessory genes largely associated with mobile genetic elements but such changes did not include any antibiotic resistance genes. These findings show significant perturbations at serotype and accessory genome level in carried pneumococcal population after two years from PCV13 introduction but the pneumococcal population was still perturbed and had not returned to a new equilibrium state.

scholarly journals Genetic Analysis Using an Isogenic Mating Pair of Aspergillus fumigatus Identifies Azole Resistance Genes and Lack of MAT Locus’s Role in Virulence

2015 ◽  
Vol 11 (4) ◽  
pp. e1004834 ◽  
Author(s):  
Liliana Losada ◽  
Janyce A. Sugui ◽  
Michael A. Eckhaus ◽  
Yun C. Chang ◽  
Stephanie Mounaud ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Aspergillus Fumigatus ◽  
Resistance Genes ◽  
Azole Resistance ◽  
Mating Pair

scholarly journals Comparative chloroplast genomic analyses revealed extensive genomic arrangement in some core and non-core caryophyllales

2019 ◽  
Vol 26 (1) ◽  
pp. 106-117 ◽  
Author(s):  
M. Ajmal Ali
Keyword(s):  
Comparative Analysis ◽  
Chloroplast Genome ◽  
Phylogenetic Relationship ◽  
Reference Genome ◽  
Gene Organization ◽  
Genomic Rearrangement ◽  
Coding Region ◽  
Genomic Arrangement ◽  
Genomic Analyses

The order Caryophyllales exhibit diverse diversity in morphology to molecules, which leads to taxonomic complexities in circumscribing especially to its families. The comparative analysis of the available chloroplast genome to detect pattern of genomic arrangement and variation is lacking; hence, the alignment pattern and genomic rearrangement across the Caryophyllales were detected, and the phylogenetic relationship among the families of the Caryophyllales based on maximum cp genes were inferred. The comparison of the Caryophyllales cp genomes based on representatives of 10 families with Taxillus chinensis as reference genome revealed that coding region were more conserved than the non-coding region; however, clpP, rpl16 and ycf15 were the most divergent coding region among all taxa. Further, the genomic rearrangement occurred in gene organization of the taxa among different families of Caryophyllales, the extensive rearrangement were observed in Amaranthaceae, Caryophyllaceae, Chenopodiaceae,Droseraceae and Cactaceae.

scholarly journals The chromosome-scale reference genome of black pepper provides insight into piperine biosynthesis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Lisong Hu ◽  
Zhongping Xu ◽  
Maojun Wang ◽  
Rui Fan ◽  
Daojun Yuan ◽  
...  
Keyword(s):  
Reference Genome ◽  
Gene Families ◽  
Black Pepper ◽  
Piper Nigrum ◽  
Comparative Genomic ◽  
Specific Gene ◽  
Phylogenomic Analysis ◽  
Genomic Analyses ◽  
Species Specific ◽  
Insight Into

Abstract Black pepper (Piper nigrum), dubbed the ‘King of Spices’ and ‘Black Gold’, is one of the most widely used spices. Here, we present its reference genome assembly by integrating PacBio, 10x Chromium, BioNano DLS optical mapping, and Hi-C mapping technologies. The 761.2 Mb sequences (45 scaffolds with an N50 of 29.8 Mb) are assembled into 26 pseudochromosomes. A phylogenomic analysis of representative plant genomes places magnoliids as sister to the monocots-eudicots clade and indicates that black pepper has diverged from the shared Laurales-Magnoliales lineage approximately 180 million years ago. Comparative genomic analyses reveal specific gene expansions in the glycosyltransferase, cytochrome P450, shikimate hydroxycinnamoyl transferase, lysine decarboxylase, and acyltransferase gene families. Comparative transcriptomic analyses disclose berry-specific upregulated expression in representative genes in each of these gene families. These data provide an evolutionary perspective and shed light on the metabolic processes relevant to the molecular basis of species-specific piperine biosynthesis.

Population structure and dynamics of insecticide resistance genes in Culex pipiens populations from Italy

Heredity ◽  
1998 ◽  
Vol 81 (3) ◽  
pp. 342-348 ◽  
Author(s):  
Francesco Silvestrini ◽  
Carlo Severini ◽  
Valeria di Pardo ◽  
Roberto Romi ◽  
Elvira de Matthaeis ◽  
...  
Keyword(s):  
Population Structure ◽  
Insecticide Resistance ◽  
Resistance Genes ◽  
Culex Pipiens ◽  
Structure And Dynamics ◽  
Population Structure And Dynamics

scholarly journals Sequencing and Comparative Genomic Analysis of pK29, a 269-Kilobase Conjugative Plasmid Encoding CMY-8 and CTX-M-3 β-Lactamases in Klebsiella pneumoniae

2007 ◽  
Vol 51 (8) ◽  
pp. 3004-3007 ◽  
Author(s):  
Ying-Tsong Chen ◽  
Tsai-Ling Lauderdale ◽  
Tsai-Lien Liao ◽  
Yih-Ru Shiau ◽  
Hung-Yu Shu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Conjugative Plasmid ◽  
Comparative Genomic ◽  
Antimicrobial Resistance Genes ◽  
Genomic Analyses ◽  
The Common

ABSTRACT A 269-kilobase conjugative plasmid, pK29, from a Klebsiella pneumoniae strain was sequenced. The plasmid harbors multiple antimicrobial resistance genes, including those encoding CMY-8 AmpC-type and CTX-M-3 extended-spectrum β-lactamases in the common backbone of IncHI2 plasmids. Mechanisms for dissemination of the resistance genes are highlighted in comparative genomic analyses.

scholarly journals Extracellular DNA Release Acts as an Antifungal Resistance Mechanism in Mature Aspergillus fumigatus Biofilms

2013 ◽  
Vol 12 (3) ◽  
pp. 420-429 ◽  
Author(s):  
Ranjith Rajendran ◽  
Craig Williams ◽  
David F. Lappin ◽  
Owain Millington ◽  
Margarida Martins ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Antifungal Susceptibility ◽  
Resistance Mechanism ◽  
Chitinase Activity ◽  
Antifungal Resistance ◽  
Extracellular Dna ◽  
Mrna Levels ◽  
Biofilm Growth ◽  
Content Type ◽  
Dnase Treatment

ABSTRACT Aspergillus fumigatus has been shown to form biofilms that are associated with adaptive antifungal resistance mechanisms. These include multidrug efflux pumps, heat shock proteins, and extracellular matrix (ECM). ECM is a key structural and protective component of microbial biofilms and in bacteria has been shown to contain extracellular DNA (eDNA). We therefore hypothesized that A. fumigatus biofilms also possess eDNA as part of the ECM, conferring a functional role. Fluorescence microscopy and quantitative PCR analyses demonstrated the presence of eDNA, which was released phase dependently (8 < 12 < 24 < 48 h). Random amplification of polymorphic DNA (RAPD) PCR showed that eDNA was identical to genomic DNA. Biofilm architectural integrity was destabilized by DNase treatment. Biochemical and transcriptional analyses showed that chitinase activity and mRNA levels of chitinase, a marker of autolysis, were significantly upregulated as the biofilm matured and that inhibition of chitinases affected biofilm growth and stability, indicating mechanistically that autolysis was possibly involved. Finally, using checkerboard assays, it was shown that combinational treatment of biofilms with DNase plus amphotericin B and caspofungin significantly improved antifungal susceptibility. Collectively, these data show that eDNA is an important structural component of A. fumigatus ECM that is released through autolysis, which is important for protection from environmental stresses, including antifungal therapy.

scholarly journals Next-Generation Sequencing and Comparative Analysis of Sequential Outbreaks Caused by Multidrug-Resistant Acinetobacter baumannii at a Large Academic Burn Center

2015 ◽  
Vol 60 (3) ◽  
pp. 1249-1257 ◽  
Author(s):  
Hajime Kanamori ◽  
Christian M. Parobek ◽  
David J. Weber ◽  
David van Duin ◽  
William A. Rutala ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Reference Genome ◽  
Index Case ◽  
Multidrug Resistant ◽  
Next Generation ◽  
The Third ◽  
Burn Center ◽  
Generation Sequencing

Next-generation sequencing (NGS) analysis has emerged as a promising molecular epidemiological method for investigating health care-associated outbreaks. Here, we used NGS to investigate a 3-year outbreak of multidrug-resistantAcinetobacter baumannii(MDRAB) at a large academic burn center. A reference genome from the index case was generated usingde novoassembly of PacBio reads. Forty-six MDRAB isolates were analyzed by pulsed-field gel electrophoresis (PFGE) and sequenced using an Illumina platform. After mapping to the index case reference genome, four samples were excluded due to low coverage, leaving 42 samples for further analysis. Multilocus sequence types (MLST) and the presence of acquired resistance genes were also determined from the sequencing data. A transmission network was inferred from genomic and epidemiological data using a Bayesian framework. Based on single-nucleotide variant (SNV) differences, this MDRAB outbreak represented three sequential outbreaks caused by distinct clones. The first and second outbreaks were caused by sequence type 2 (ST2), while the third outbreak was caused by ST79. For the second outbreak, the MLST and PFGE results were discordant. However, NGS-based SNV typing detected a recombination event and consequently enabled a more accurate phylogenetic analysis. The distribution of resistance genes varied among the three outbreaks. The first- and second-outbreak strains possessed ablaOXA-23-likegroup, while the third-outbreak strains harbored ablaOXA-40-likegroup. NGS-based analysis demonstrated the superior resolution of outbreak transmission networks for MDRAB and provided insight into the mechanisms of strain diversification between sequential outbreaks through recombination.

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