Biology subjects

Alt, D.

Publications and source records attributed to Alt, D..

3 recordsLinked to original sources

bioRxiv2020

A pseudomolecule assembly of the Rocky Mountain elk genome reveals putative immune system gene loss near chromosomal fissions

Rocky Mountain elk (Cervus canadensis) is a major reservoir for Brucella abortus in the Greater Yellowstone area, which has significant economic implications to the cattle industry. Vaccination attempts against intracellular bacterial diseases in elk populations have not been successful due to a negligible adaptive cellular immune response. A lack of genomic resources has impeded attempts to better understand why vaccination does not induce protective immunity. To overcome this limitation, PacBio, Illumina, and HiC sequencing with a total of 686-fold coverage was used to assemble the elk genome into 35 pseudomolecules. A robust gene annotation was generated resulting in 18,013 gene models and 33,422 mRNAs. The accuracy of the assembly was assessed using synteny to the red deer and cattle genomes identifying several chromosomal rearrangements, fusions and fissions. Because this genome assembly and annotation provide a foundation for genome-enabled exploration of Cervus species, we demonstrate its utility by exploring the conservation of immune system-related genes. We conclude by comparing cattle immune system-related genes to the elk genome, revealing nine putative gene losses in elk. Author SummaryBrucellosis, also known as contagious abortion, is a bacterial disease that commonly affects livestock and remains prevalent in Rocky Mountain elk (Cervus canadensis). Since the 1920s the USDA has led a program to eradicate Brucellosis from cattle, yet wild Rocky Mountain elk continue to be a source of transmission. Attempts to vaccinate wild elk herds have been unsuccessful, due to a poor and short-lived immune response. To investigate the genetic basis for this inherent difference, we created the first genome and annotation for the Rocky Mountain elk. This genome assembly is of the highest quality and contains single linear sequences for all 35 chromosomes. In order to generate gene models, an array of RNA-Seq data and proteins from many different organ tissues and cells were used in gene prediction software. Specifically, we compare cattle immune system genes with the Rocky Mountain elk, revealing the putative loss of nine immune-system related genes in elk.

genomics↗

bioRxiv2020

Global population genomic analysis of Mycoplasma bovis isolates reveals transcontinental variations and potential virulence genes

Among more than twenty species belonging to the class Mollecutes, Mycoplasma bovis is the most common cause of bovine mycoplasmosis in North America and Europe. Bovine mycoplasmosis causes significant economic loss in the cattle industry. The number of M. bovis positive herds has recently increased in North America and Europe. Since antibiotic treatment is ineffective and no efficient vaccine is available, M. bovis-induced mycoplasmosis is primarily controlled by herd management measures such as the restriction of moving infected animals out of the herds and culling of infected animals or shedders. To better understand the population structure and genomic factors that may contribute to its transmission, we sequenced 147 M. bovis strains isolated from four different countries and hosts, primarily cattle. We performed a large-scale comparative analysis of M. bovis genomes by integrating 104 publicly available genomes and our dataset (251 total genomes). A whole genome-single nucleotide polymorphism (SNP)-based phylogeny revealed that M. bovis population structure is composed of five clades with one of the isolates clustering with the outgroup M. agalactiae. These isolates were found to cluster with those from Canada, Israel, Lithuania, and Switzerland, suggesting trans-continental transmission of the strains. We also validated a previous report suggesting minimum divergence in isolates of Australian origin, which grouped within a single clade along with strains from China and Israel. However, no observable pattern of host association in M. bovis genomes was found in this study. Our comparative genome analysis also revealed that M. bovis has an open pangenome with a large breadth of unexplored diversity of genes. Analysis of vsp gene-host association revealed a single vsp significantly associated with bovine isolates that may be targeted for diagnostics or vaccine development. Our study also found that M. bovis genome harbors a large number of IS elements, including a novel 1624 bp IS element, and ISMbov9. Collectively, the genome data and the whole genome-based population analysis in this study may help to develop control measures to reduce the incidence of M. bovis-induced mycoplasmosis in cattle and/or to identify candidate genes for vaccine development.

microbiology↗

bioRxiv2020

A Live Attenuated Vaccine Model Confers Cross-Protective Immunity Against Different Species of Leptospira spp.

Leptospirosis is the leading zoonotic disease in terms of morbidity and mortality worldwide with a great health and economic impact in both humans and animals. Effective prevention is urgently needed as rapid urbanization, climate change and drivers of disease transmission continue to intensify. The key challenge has been developing a widely-applicable vaccine that protects against the 13 different pathogenic species and >300 serovars that can cause leptospirosis, providing a major public health benefit and opportunity to leverage One Health approaches. Live attenuated mutants that can boost immunity and induce protection are enticing vaccine candidates and poorly explored in the field. We evaluated a recently characterized motility-deficient mutant lacking the expression of a flagellar protein, FcpA. Although the fcpA- mutant has lost its ability to penetrate mucous membranes and cause disease, a transient bacteremia prior to clearance by the host immune response was observed. In two animal models, immunization with a single dose of the fcpA- mutant was sufficient to induce robust anti-protein antibodies response that promoted protection against infection with different Leptospira spp. species. Furthermore, characterization of the immune response identified a small repertoire of biologically relevant proteins that are highly conserved among pathogenic Leptospira species and potential correlates of cross-protective immunity.

microbiology↗