Genomic plasticity and rapid host switching can promote the evolution of generalism : a case study in the zoonotic pathogen Campylobacter

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/I02464X/1, the Medical Research Council (MRC) grants MR/M501608/1 and MR/L015080/1, and the Wellcome Trust grant 088786/C/09/Z. GM was supported by a NISCHR Health Research Fellowship (HF-14–13).Peer reviewedPublisher PD

Dimethyl 5,5′-methyl­enebis(2-hy­droxy­benzoate)

In the title compound, C17H16O6, the two methyl salicylate moieties are related by crystallographic twofold rotational symmetry with the two benzene rings close to being perpendicular [inter-ring dihedral angle = 86.6 (8)°]. Intra­molecular phenolic O—H⋯O hydrogen bonds with carboxyl O-atom acceptors are present, with these groups also involved in centrosymmetric cyclic inter­molecular O—H⋯O hydrogen-bonding associations [graph set R 2 2(4)], giving infinite chains extending across (101)

The impact of host metapopulation structure on the population genetics of colonizing bacteria

Many key bacterial pathogens are frequently carried asymptomatically, and the emergence and spread of these opportunistic pathogens can be driven, or mitigated, via demographic changes within the host population. These inter-host transmission dynamics combine with basic evolutionary parameters such as rates of mutation and recombination, population size and selection, to shape the genetic diversity within bacterial populations. Whilst many studies have focused on how molecular processes underpin bacterial population structure, the impact of host migration and the connectivity of the local populations has received far less attention. A stochastic neutral model incorporating heightened local transmission has been previously shown to fit closely with genetic data for several bacterial species. However, this model did not incorporate transmission limiting population stratification, nor the possibility of migration of strains between subpopulations, which we address here by presenting an extended model. We study the consequences of migration in terms of shared genetic variation and show by simulation that the previously used summary statistic, the allelic mismatch distribution, can be insensitive to even large changes in microepidemic and migration rates. Using likelihood-free inference with genotype network topological summaries we fit a simpler model to commensal and hospital samples from the common nosocomial pathogens Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium. Only the hospital data for E. faecium display clearly marked deviations from the model predictions which may be attributable to its adaptation to the hospital environment

Crowdfunding Models, Strategies, and Choices Between Them

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Draft Genomes, Phylogenetic Reconstruction, and Comparative Genomics of Two Novel Cohabiting Bacterial Symbionts Isolated from Frankliniella occidentalis

Obligate bacterial symbionts are widespread in many invertebrates, where they are often confined to specialized host cells and are transmitted directly from mother to progeny. Increasing numbers of these bacteria are being characterized but questions remain about their population structure and evolution. Here we take a comparative genomics approach to investigate two prominent bacterial symbionts (BFo1 and BFo2) isolated from geographically separated populations of western flower thrips, Frankliniella occidentalis. Our multifaceted approach to classifying these symbionts includes concatenated multilocus sequence analysis (MLSA) phylogenies, ribosomal multilocus sequence typing (rMLST), construction of whole-genome phylogenies, and in-depth genomic comparisons. We showed that the BFo1 genome clusters more closely to species in the genus Erwinia, and is a putative close relative to Erwinia aphidicola. BFo1 is also likely to have shared a common ancestor with Erwinia pyrifoliae/Erwinia amylovora and the nonpathogenic Erwinia tasmaniensis and genetic traits similar to Erwinia billingiae. The BFo1 genome contained virulence factors found in the genus Erwinia but represented a divergent lineage. In contrast, we showed that BFo2 belongs within the Enterobacteriales but does not group closely with any currently known bacterial species. Concatenated MLSA phylogenies indicate that it may have shared a common ancestor to the Erwinia and Pantoea genera, and based on the clustering of rMLST genes, it was most closely related to Pantoea ananatis but represented a divergent lineage. We reconstructed a core genome of a putative common ancestor of Erwinia and Pantoea and compared this with the genomes of BFo bacteria. BFo2 possessed none of the virulence determinants that were omnipresent in the Erwinia and Pantoea genera. Taken together, these data are consistent with BFo2 representing a highly novel species that maybe related to known Pantoea

Trycycler: consensus long-read assemblies for bacterial genomes

While long-read sequencing allows for the complete assembly of bacterial genomes, long-read assemblies contain a variety of errors. Here, we present Trycycler, a tool which produces a consensus assembly from multiple input assemblies of the same genome. Benchmarking showed that Trycycler assemblies contained fewer errors than assemblies constructed with a single tool. Post-assembly polishing further reduced errors and Trycycler+polishing assemblies were the most accurate genomes in our study. As Trycycler requires manual intervention, its output is not deterministic. However, we demonstrated that multiple users converge on similar assemblies that are consistently more accurate than those produced by automated assembly tools

Genome-wide association of functional traits linked with<i> Campylobacter jejuni </i>survival from farm to fork

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, primarily associated with the consumption of contaminated poultry. C. jejuni lineages vary in host range and prevalence in human infection, suggesting differences in survival throughout the poultry processing chain. From 7,343 MLST-characterised isolates, we sequenced 600 C. jejuni and C. coli isolates from various stages of poultry processing and clinical cases. A genome-wide association study (GWAS) in C. jejuni ST-21 and ST-45 complexes identified genetic elements over-represented in clinical isolates that increased in frequency throughout the poultry processing chain. Disease-associated SNPs were distinct in these complexes, sometimes organised in haplotype blocks. The function of genes containing associated elements was investigated, demonstrating roles for cj1377c in formate metabolism, nuoK in aerobic survival and oxidative respiration, and cj1368-70 in nucleotide salvage. This work demonstrates the utility of GWAS for investigating transmission in natural zoonotic pathogen populations and provides evidence that major C. jejuni lineages have distinct genotypes associated with survival, within the host specific niche, from farm to fork. </p

Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders