Browsing by Author "Todd, S. Michelle"

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    Adrenocortical Challenge Response and Genomic Analyses in Scottish Terriers With Increased Alkaline Phosphate Activity
    Zimmerman, Kurt L.; Panciera, David L.; Hoeschele, Ina; Monroe, William E.; Todd, S. Michelle; Werre, Stephen R.; LeRoith, Tanya; Fecteau, Kellie; Lake, Bathilda B. (Frontiers, 2018-10-09)
    Scottish terriers (ST) frequently have increased serum alkaline phosphatase (ALP) of the steroid isoform. Many of these also have high serum concentrations of adrenal sex steroids. The study’s objective was to determine the cause of increased sex steroids in ST with increased ALP. Adrenal gland suppression and stimulation were compared by low dose dexamethasone (LDDS), human chorionic gonadotropin (HCG) and adrenocorticotropic hormone (ACTH) response tests. Resting plasma pituitary hormones were measured. Steroidogenesis-related mRNA expression was evaluated in six ST with increased ALP, eight dogs of other breeds with pituitary-dependent hyperadrenocorticism (HAC), and seven normal dogs. The genome-wide association of single nucleotide polymorphisms (SNP) with ALP activity was evaluated in 168 ST. ALP (reference interval 8–70 U/L) was high in all ST (1,054 U/L) and HAC (985 U/L) dogs. All HAC dogs and 2/8 ST had increased cortisol post-ACTH administration. All ST and 2/7 Normal dogs had increased sex steroids post-ACTH. ST and Normal dogs had similar post-challenge adrenal steroid profiles following LDDS and HCG. Surprisingly, mRNA of hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2) was lower in ST and Normal dogs than HAC. HSD17B2 facilities metabolism of sex steroids. A SNP region was identified on chromosome 5 in proximity to HSD17B2 that correlated with increased serum ALP. ST in this study with increased ALP had a normal pituitary-adrenal axis in relationship to glucocorticoids and luteinizing hormone.We speculate the identified SNP and HSD17B2 gene may have a role in the pathogenesis of elevated sex steroids and ALP in ST.
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    Complete Genome Sequence of Providencia stuartii CMC-4104, Isolated from a Human Splenic Abscess, Containing Multiple Copies of NDM-1 and PER-1 Carbapenem Resistance Genes
    Rao, Jayasimha; Stornelli, Nicholas K.; Everson, Nathan A.; McDaniel, Lauren F.; Gomez De La Espriella, Mariana; Faulhaber, Jason R.; Todd, S. Michelle; Lahmers, Kevin K.; Jensen, Roderick V. (American Society for Microbiology, 2022-08-04)
    We report the complete genome sequence of a clinical isolate of Providencia stuartii strain CMC-4104, isolated from a splenic abscess. Oxford Nanopore Technologies (ONT) and Illumina sequencing reads were assembled using Geneious to generate a 4,504,925-bp circular chromosome containing multiple copies of the NDM-1 and PER-1 genes in a genomic resistance island.
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    Fusobacterium Genomics Using MinION and Illumina Sequencing Enables Genome Completion and Correction
    Todd, S. Michelle; Settlage, Robert E.; Lahmers, Kevin K.; Slade, Daniel J. (American Society for Microbiology, 2018)
    Understanding the virulence mechanisms of human pathogens from the genus Fusobacterium has been hindered by a lack of properly assembled and annotated genomes. Here we report the first complete genomes for seven Fusobacterium strains, as well as resequencing of the reference strain Fusobacterium nucleatum subsp. nucleatum ATCC 25586 (total of seven species; total of eight genomes). A highly efficient and cost-effective sequencing pipeline was achieved using sample multiplexing for short-read Illumina (150 bp) and long-read Oxford Nanopore Min- ION (80 kbp) platforms, coupled with genome assembly using the open-source software Unicycler. Compared to currently available draft assemblies (previously 24 to 67 contigs), these genomes are highly accurate and consist of only one complete chromosome. We present the complete genome sequence of F. nucleatum subsp. nucleatum ATCC 23726, a genetically tractable and biomedically important strain and, in addition, reveal that the previous F. nucleatum subsp. nucleatum ATCC 25586 genome assembly contains a 452-kb genomic inversion that has been corrected using our sequencing and assembly pipeline. To enable genomic analyses by the scientific community, we concurrently used these genomes to launch FusoPortal, a repository of interactive and downloadable genomic data, genome maps, gene annotations, and protein functional analyses and classifications. In summary, this report provides detailed methods for accurately sequencing, assembling, and annotating Fusobacterium genomes, while focusing on using open-source software to foster the availability of reproducible and open data. This resource will enhance efforts to properly identify virulence proteins that may contribute to a repertoire of diseases that includes periodontitis, preterm birth, and colorectal cancer.
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    Regulatory T Cells in Arterivirus and Coronavirus Infections: Do They Protect Against Disease or Enhance it?
    Cecere, Thomas E.; Todd, S. Michelle; LeRoith, Tanya (MDPI, 2012-05-01)
    Regulatory T cells (Tregs) are a subset of T cells that are responsible for maintaining peripheral immune tolerance and homeostasis. The hallmark of Tregs is the expression of the forkhead box P3 (FoxP3) transcription factor. Natural regulatory T cells (nTreg) are a distinct population of T cells that express CD4 and FoxP3. nTregs develop in the thymus and function in maintaining peripheral immune tolerance. Other CD4+, CD4-CD8-, and CD8+CD28- T cells can be induced to acquire regulatory function by antigenic stimulation, depending on the cytokine milieu. Inducible (or adaptive) Tregs frequently express high levels of the interleukin 2 receptor (CD25). Atypical Tregs express FoxP3 and CD4 but have no surface expression of CD25. Type 1 regulatory T cells (Tr1 cells) produce IL-10, while T helper 3 cells (Th3) produce TGF-β. The function of inducible Tregs is presumably to maintain immune homeostasis, especially in the context of chronic inflammation or infection. Induction of Tregs in coronaviral infections protects against the more severe forms of the disease attributable to the host response. However, arteriviruses have exploited these T cell subsets as a means to dampen the immune response allowing for viral persistence. Treg induction or activation in the pathogenesis of disease has been described in both porcine reproductive and respiratory syndrome virus, lactate dehydrogenase elevating virus, and mouse hepatitis virus. This review discusses the development and biology of regulatory T cells in the context of arteriviral and coronaviral infection.
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    Theileria orientalis Ikeda Genotype in Cattle, Virginia, USA
    Oakes, Vanessa J.; Yabsley, Michael J.; Schwartz, Diana; LeRoith, Tanya; Bissett, Carolynn; Broaddus, Charles; Schlater, Jack L.; Todd, S. Michelle; Boes, Katie M.; Brookhart, Meghan; Lahmers, Kevin K. (Centers for Disease Control and Prevention, 2019-09)
    Theileria orientalis Ikeda genotype is a parasite that causes a disease in cattle that results in major economic issues in Asia, New Zealand, and Australia. The parasite is transmitted by Haemaphysalis longicornis ticks, which have recently been reported in numerous states throughout the eastern United States. Concurrently, cattle in Virginia showed clinical signs consistent with a hemoprotozoan infection. We used amplicons specific for the major piroplasm surface protein and small subunit rDNA of piroplasms to test blood samples from the cattle by PCR. Bidirectional Sanger sequencing showed sequences with 100% identity with T. orientalis Ikeda genotype 2 sequences. We detected the parasite in 3 unrelated herds and from various animals sampled at 2 time points. Although other benign T. orientalis genotypes are endemic to the United States, detection of T. orientalis Ikeda genotype might represent a risk for the cattle industry in Virginia.
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    A U.S. isolate of Theileria orientalis, Ikeda genotype, is transmitted to cattle by the invasive Asian longhorned tick, Haemaphysalis longicornis
    Dinkel, Kelcey D.; Herndon, David R.; Noh, Susan M.; Lahmers, Kevin K.; Todd, S. Michelle; Ueti, Massaro W.; Scoles, Glen A.; Mason, Kathleen L.; Fry, Lindsay M. (BMC, 2021-03-16)
    Background: Theileria orientalis is a tick-borne hemoparasite that causes anemia, ill thrift, and death in cattle globally. The Ikeda strain of T.orientalis is more virulent than other strains, leading to severe clinical signs and death of up to 5% of affected animals. Within the Asia–Pacific region, where it affects 25% of Australian cattle, T.orientalis Ikeda has a significant economic impact on the cattle industry. In 2017, T.orientalis Ikeda was detected in a cattle herd in Albermarle County, Virginia, United States. Months earlier, the U.S. was alerted to the invasion of the Asian longhorned tick, Haemaphysalis longicornis, throughout the eastern U.S. Abundant H.longicornis ticks were identified on cattle in the T.orientalis-affected herd in VA, and a subset of ticks from the environment were PCR-positive for T.orientalis Ikeda. A strain of T.orientalis from a previous U.S. outbreak was not transmissible by H.longicornis; however, H.longicornis is the primary tick vector of T.orientalis Ikeda in other regions of the world. Thus, the objective of this study was to determine whether invasive H.longicornis ticks in the U.S. are competent vectors of T.orientalis Ikeda. Methods: Nymphal H.longicornis ticks were fed on a splenectomized calf infected with the VA-U.S.-T.orientalis Ikeda strain. After molting, a subset of adult ticks from this cohort were dissected, and salivary glands assayed for T.orientalis Ikeda via qPCR. The remaining adult ticks from the group were allowed to feed on three calves. Calves were subsequently monitored for T.orientalis Ikeda infection via blood smear cytology and PCR. Results: After acquisition feeding on a VA-U.S.-T.orientalis Ikeda-infected calf as nymphs, a subset of molted adult tick salivary glands tested positive by qPCR for T.orientalis Ikeda. Adult ticks from the same cohort successfully transmitted T.orientalis Ikeda to 3/3 naïve calves, each of which developed parasitemia reaching 0.4–0.9%. Conclusions: Our findings demonstrate that U.S. H.longicornis ticks are competent vectors of the VA-U.S.-T.orientalis Ikeda strain. This data provides important information for the U.S. cattle industry regarding the potential spread of this parasite and the necessity of enhanced surveillance and control measures.[Figure not available: see fulltext.].