Project description:Clonal emergence is a major driver for changes in bacterial disease epidemiology. Recently, it has been proposed that episodic emergence of novel, hypervirulent clones of group A Streptococcus (GAS) results from horizontal gene transfer (HGT) and recombination events leading to increased expression of the cytotoxins Nga (NADase) and SLO (streptolysin O). We previously described a gene fusion event involving the gene encoding the GAS M protein (emm) and an adjacent M-like protein (enn) in the emm4 GAS population, a GAS emm type that lacks the hyaluronic acid capsule. Using whole genome sequencing of a temporally and geographically diverse set of 1,127 isolates, we discovered that the North American emm4 GAS population has undergone clonal replacement with emergent GAS strains completely replacing historical isolates by 2017. Emergent emm4 GAS strains were defined by a handful of small genetic variations, including the emm-enn gene fusion, and showed a marked in vitro growth defect compared to historical strains. In contrast to other previously described GAS clonal emergence events, emergent emm4 GAS lacked significant HGT events and showed no significant increase in transcript levels of nga/slo toxin gene via RNA sequencing and quantitative real-time PCR analysis relative to historic strains. Despite the in vitro growth differences, emergent emm4 GAS strains demonstrated hypervirulence in mouse and ex vivo growth in human blood compared to historical strains. Thus, these data detail the emergence and dissemination of a hypervirulent acapsular GAS clone defined by small genetic variation thereby defining a novel model for GAS strain replacement.
2021-05-05 | GSE160737 | GEO
Project description:Antimicrobial Susceptibility in Historical C. difficile Isolates
Project description:Despite high vaccination coverage, pertussis is on the rise in many countries including Czech Republic. To better understand B. pertussis resurgence we compared the changes in genome structures between Czech vaccine and circulating strains and subsequently, we determined how these changes translated into global transcriptomic and proteomic profiles. The whole-genome sequencing revealed that both historical and recent isolates of B. pertussis display substantial variation in genome organization and cluster separately. The RNA-seq and LC-MS/MS analyses indicate that these variations translated into discretely separated transcriptomic and proteomic profiles. Compared to vaccine strains, recent isolates displayed increased expression of flagellar genes and decreased expression of polysaccharide capsule operon. Czech strains (Bp46, K10, Bp155, Bp318 and Bp6242)exhibited increased expression of T3SS and sulphate metabolism genes when compared to Tohama I. In spite of 50 years of vaccination the Czech vaccine strains (VS67, VS393 and VS401) differ from recent isolates to a lesser extent than from another vaccine strain Tohama I.
2021-09-08 | PXD015184 | Pride
Project description:Whole genome sequencing of historical Listeria monocytogenes isolates
| PRJNA906255 | ENA
Project description:Historical Mycobacterium bovis isolates of animal origin, Canada
Project description:Free-breeding dogs have occupied the Galápagos islands at least since the 1830s, however, it was not until the 1900s that dog populations grew substantially, endangering wildlife and spreading disease. In 1981, authorities sanctioned the culling of free-roaming dogs. Yet there are currently large free-roaming dog populations of unknown ancestry on the islands of Isabela and Santa Cruz, whose ancestry has never been assessed on a genome-wide scale. Thus, we performed a complete genomic analysis of the current Galápagos dog population as well as historical Galápagos dogs sampled between 1969 and 2003, testing for population structure, admixture, and shared ancestry. Our dataset included samples from 187 modern and six historical Galápagos dogs, together with whole genome sequence from over 2,000 modern purebred and village dogs. Our results indicate that modern Galápagos dogs are recently admixed with purebred dogs but show no evidence of a population bottleneck related to the culling. Additionally, IBD analyses reveal evidence of shared shepherd-dog ancestry in the historical Galápagos dogs. Overall, our results demonstrate that the 1980s culling of dogs was ineffective in controlling population size and did little to reduce genetic diversity, instead producing a stable and expanding population with genomic signatures of historical dogs remaining today. The insights from this study can be used to improve population control strategies for the Galápagos Islands and other endangered endemic communities worldwide.
Project description:In C. elegans worms, epigenetic information transmits transgenerationally. Still, it is unknown whether the effects transfer to the next generation inside or outside of the nucleus. Here we use the tractability of gene-specific double-stranded RNA-induced silencing to demonstrate that RNAi can be inherited independently of any nuclear factors via mothers that are genetically engineered to transmit only their ooplasm but not the oocytes’ nuclei to the next generation. We characterize the mechanisms and, utilizing RNA sequencing, chimeric worms and sequence polymorphism between different isolates, identify endogenous small RNAs which, similarly to exogenous siRNAs, are inherited in a nucleus-independent manner. From an historical perspective, these results might be regarded as partial vindication of discredited cytoplasmic inheritance theories from the 19th century, such as Darwin’s “pangenesis” theory.