Norris, M. H. | Search bioRxiv

bioRxiv2024

Phylogeographic patterns of Escherichia coli isolated from white-tailed deer, Odocoileus virginianus , during necropsy in a farmed deer surveillance program

White-tailed deer (Odocoileus virginianus) (WTD) farms are distributed throughout Florida and number nearly 400. The Cervidae Health Research Initiative (CHeRI) is an initiative that investigates disease and health of farmed cervids statewide. Within the Florida industry, Epizootic Hemorrhagic disease virus (EHDV) and Bluetongue virus (BTV) are major causes of disease and associated economic losses. Often, deer survive EHDV or BTV infections but succumb to secondary bacterial infections, including Escherichia coli. E. coli can be opportunistic with severe illness or death occurring in hosts weakened from viral infection. We investigated presumptive E. coli strains isolated from WTD during necropsy investigations. Genomic DNA was extracted and whole genome sequenced from 61 suspect E. coli isolates. Exploratory spatial data analysis (ESDA) of the distribution of E. coli phylotypes, distribution of E. coli, and deer between ranches was performed. We examined phylogenetic relationships between isolates, categorized by ranch and year and compared to all reported E. coli isolates in Florida from EnteroBase. One strain was Enterobacter hormaechei and the other 60 were E. coli. Two E. coli strains were toxigenic. Deer isolates represented 7 phylogroups with B1 being the most prevalent (45/60) and geographically widespread (14/16 counties reporting E. coli). Phylogroup A was the second most prevalent phylogroup. In at least two instances two phylogroups were present within a single animal. We found that deer isolates spanned many of known phylotypes in Florida from animals and humans. Diversity patterns suggest deer are infected locally with most animals on ranches having high genomic similarity within phylogroups. *Sequence data from this article have been deposited in the National Center for Biotechnology Information (NCBI) database under BioProject PRJNA1183872.

genomics↗

bioRxiv2021

Genome-scale CRISPR Screens Identify Host Factors that Promote Human Coronavirus Infection

The COVID-19 pandemic has resulted in 153 million infections and 3.2 million deaths as of May 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as potentially antigenically distinct SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. While we identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication, we also identified a substantial number of novel genes and pathways. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. Finally, we identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Overall, our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development. One Sentence SummaryGenome-wide CRISPR screens identified host factors that promote human coronavirus infection, revealing novel antiviral drug targets.

microbiology↗