Scholarly Works, Virginia-Maryland College of Veterinary Medicine

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Research articles, presentations, and other scholarship


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  • Peeling back the many layers of competitive exclusion
    Maurer, John J.; Cheng, Ying; Pedroso, Adriana; Thompson, Kasey K.; Akter, Shamima; Kwan, Tiffany; Morota, Gota; Kinstler, Sydney; Porwollik, Steffen; McClelland, Michael; Escalante-Semerena, Jorge C.; Lee, Margie D. (Frontiers, 2024-03-21)
    Baby chicks administered a fecal transplant from adult chickens are resistant to Salmonella colonization by competitive exclusion. A two-pronged approach was used to investigate the mechanism of this process. First, Salmonella response to an exclusive (Salmonella competitive exclusion product, Aviguard®) or permissive microbial community (chicken cecal contents from colonized birds containing 7.85 Log₁ₒ Salmonella genomes/gram) was assessed ex vivo using a S. typhimurium reporter strain with fluorescent YFP and CFP gene fusions to rrn and hilA operon, respectively. Second, cecal transcriptome analysis was used to assess the cecal communities’ response to Salmonella in chickens with low (≤5.85 Log₁ₒ genomes/g) or high (≥6.00 Log₁ₒ genomes/g) Salmonella colonization. The ex vivo experiment revealed a reduction in Salmonella growth and hilA expression following co-culture with the exclusive community. The exclusive community also repressed Salmonella’s SPI-1 virulence genes and LPS modification, while the anti-virulence/inflammatory gene avrA was upregulated. Salmonella transcriptome analysis revealed significant metabolic disparities in Salmonella grown with the two different communities. Propanediol utilization and vitamin B12 synthesis were central to Salmonella metabolism co-cultured with either community, and mutations in propanediol and vitamin B12 metabolism altered Salmonella growth in the exclusive community. There were significant differences in the cecal community’s stress response to Salmonella colonization. Cecal community transcripts indicated that antimicrobials were central to the type of stress response detected in the low Salmonella abundance community, suggesting antagonism involved in Salmonella exclusion. This study indicates complex community interactions that modulate Salmonella metabolism and pathogenic behavior and reduce growth through antagonism may be key to exclusion.
  • De Novo Assembly and Annotation of 11 Diverse Shrub Willow (Salix) Genomes Reveals Novel Gene Organization in Sex-Linked Regions
    Hyden, Brennan; Feng, Kai; Yates, Timothy B.; Jawdy, Sara; Cereghino, Chelsea; Smart, Lawrence B.; Muchero, Wellington (MDPI, 2023-02-02)
    Poplar and willow species in the Salicaceae are dioecious, yet have been shown to use different sex determination systems located on different chromosomes. Willows in the subgenus Vetrix are interesting for comparative studies of sex determination systems, yet genomic resources for these species are still quite limited. Only a few annotated reference genome assemblies are available, despite many species in use in breeding programs. Here we present de novo assemblies and annotations of 11 shrub willow genomes from six species. Copy number variation of candidate sex determination genes within each genome was characterized and revealed remarkable differences in putative master regulator gene duplication and deletion. We also analyzed copy number and expression of candidate genes involved in floral secondary metabolism, and identified substantial variation across genotypes, which can be used for parental selection in breeding programs. Lastly, we report on a genotype that produces only female descendants and identified gene presence/absence variation in the mitochondrial genome that may be responsible for this unusual inheritance.
  • Escherichia coli-associated granulomatous colitis in a cat
    Safian, Alexander M.; Bolton, Timothy (Wiley, 2021)
    A 6-year-old male castrated domestic shorthair cat was evaluated for a 6-month history of haematochezia, mucoid diarrhoea, tenesmus and rectal prolapse. Colonic histopathology revealed multifocal mucosal ulceration and lamina propria infiltration with large numbers of periodic acid-Schiff-positivemacrophages. Large clusters of intracellular Escherichia coli were confirmed with fluorescence in situ hybridization testing, similar to that seen in dogs with granulomatous colitis. An 8-week course of marbofloxacin resulted in resolution of clinical signs; however, recurrence occurred 4 weeks later. A 12-week course of marbofloxacin resulted in disease remission for which the cat still remains free of clinical signs (15 months). Escherichia coli-associated granulomatous colitis, although reported with rarity in this species, is an important infectious cause of chronic large intestinal disease in the cat.
  • Endemicity of Yaws and Seroprevalence of Treponema pallidum Antibodies in Nonhuman Primates, Kenya
    Zimmerman, Dawn M.; Hardgrove, Emily H.; von Fricken, Michael E.; Kamau, Joseph; Chai, Daniel; Mutura, Samson; Kivali, Velma; Hussein, Fatima; Ambala, Peris; Surmat, Andrea; Maina, Joseph G.; Knauf, Sascha (2019-11)
    Human yaws has historically been endemic to Kenya, but current epidemiologic data are lacking. We report seroprevalence for Treponema pallidum antibodies in olive baboons (Papio anubis) and vervet monkeys (Chlorocebus pygerythrus) in Laikipia County, Kenya. Our results suggest endemicity of the yaws bacterium in monkeys, posing a possible zoonotic threat to humans.
  • Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function
    McDaniel, Dylan K.; Ringel-Scaia, Veronica M.; Morrison, Holly A.; Coutermarsh-Ott, Sheryl; Council-Troche, McAlister; Angle, Jonathan W.; Perry, Justin B.; Davis, Grace; Leng, Weinan; Minarchick, Valerie; Yang, Yi; Chen, Bo; Reece, Sky W.; Brown, David A.; Cecere, Thomas E.; Brown, Jared M.; Gowdy, Kymberly M.; Hochella, Michael F. Jr.; Allen, Irving C. (Frontiers, 2019-11-28)
    Coal is one of the most abundant and economic sources for global energy production. However, the burning of coal is widely recognized as a significant contributor to atmospheric particulate matter linked to deleterious respiratory impacts. Recently, we have discovered that burning coal generates large quantities of otherwise rare Magnéli phase titanium suboxides from TiO2 minerals naturally present in coal. These nanoscale Magnéli phases are biologically active without photostimulation and toxic to airway epithelial cells in vitro and to zebrafish in vivo. Here, we sought to determine the clinical and physiological impact of pulmonary exposure to Magnéli phases using mice as mammalian model organisms. Mice were exposed to the most frequently found Magnéli phases, Ti6O11, at 100 parts per million (ppm) via intratracheal administration. Local and systemic titanium concentrations, lung pathology, and changes in airway mechanics were assessed. Additional mechanistic studies were conducted with primary bone marrow derived macrophages. Our results indicate that macrophages are the cell type most impacted by exposure to these nanoscale particles. Following phagocytosis, macrophages fail to properly eliminate Magnéli phases, resulting in increased oxidative stress, mitochondrial dysfunction, and ultimately apoptosis. In the lungs, these nanoparticles become concentrated in macrophages, resulting in a feedback loop of reactive oxygen species production, cell death, and the initiation of gene expression profiles consistent with lung injury within 6 weeks of exposure. Chronic exposure and accumulation of Magnéli phases ultimately results in significantly reduced lung function impacting airway resistance, compliance, and elastance. Together, these studies demonstrate that Magnéli phases are toxic in the mammalian airway and are likely a significant nanoscale environmental pollutant, especially in geographic regions where coal combustion is a major contributor to atmospheric particulate matter.
  • The Komodo dragon (Varanus komodoensis) genome and identification of innate immunity genes and clusters
    van Hoek, Monique L.; Prickett, M. D.; Settlage, Robert E.; Kang, Lin; Michalak, Pawel; Vliet, Kent A.; Bishop, Barney M. (2019-08-30)
    Background We report the sequencing, assembly and analysis of the genome of the Komodo dragon (Varanus komodoensis), the largest extant lizard, with a focus on antimicrobial host-defense peptides. The Komodo dragon diet includes carrion, and a complex milieu of bacteria, including potentially pathogenic strains, has been detected in the saliva of wild dragons. They appear to be unaffected, suggesting that dragons have robust defenses against infection. While little information is available regarding the molecular biology of reptile immunity, it is believed that innate immunity, which employs antimicrobial host-defense peptides including defensins and cathelicidins, plays a more prominent role in reptile immunity than it does in mammals. . Results High molecular weight genomic DNA was extracted from Komodo dragon blood cells. Subsequent sequencing and assembly of the genome from the collected DNA yielded a genome size of 1.6 Gb with 45x coverage, and the identification of 17,213 predicted genes. Through further analyses of the genome, we identified genes and gene-clusters corresponding to antimicrobial host-defense peptide genes. Multiple β-defensin-related gene clusters were identified, as well as a cluster of potential Komodo dragon ovodefensin genes located in close proximity to a cluster of Komodo dragon β-defensin genes. In addition to these defensins, multiple cathelicidin-like genes were also identified in the genome. Overall, 66 β-defensin genes, six ovodefensin genes and three cathelicidin genes were identified in the Komodo dragon genome. Conclusions Genes with important roles in host-defense and innate immunity were identified in this newly sequenced Komodo dragon genome, suggesting that these organisms have a robust innate immune system. Specifically, multiple Komodo antimicrobial peptide genes were identified. Importantly, many of the antimicrobial peptide genes were found in gene clusters. We found that these innate immunity genes are conserved among reptiles, and the organization is similar to that seen in other avian and reptilian species. Having the genome of this important squamate will allow researchers to learn more about reptilian gene families and will be a valuable resource for researchers studying the evolution and biology of the endangered Komodo dragon.
  • Genomic divergence and adaptive convergence in Drosophila simulans from Evolution Canyon, Israel
    Kang, Lin; Rashkovetsky, Eugenia; Michalak, Katarzyna; Garner, Harold R.; Mahaney, James E.; Rzigalinski, Beverly A.; Korol, Abraham B.; Nevo, Eviatar; Michalak, Pawel (2019-06-11)
    Biodiversity refugia formed by unique features of the Mediterranean arid landscape, such as the dramatic ecological contrast of "Evolution Canyon," provide a natural laboratory in which local adaptations to divergent microclimate conditions can be investigated. Significant insights have been provided by studies of Drosophila melanogaster diversifying along the thermal gradient in Evolution Canyon, but a comparative framework to survey adaptive convergence across sister species at the site has been lacking. To fill this void, we present an analysis of genomic polymorphism and evolutionary divergence of Drosophila simulans, a close relative of Drosophila melanogaster with which it co-occurs on both slopes of the canyon. Our results show even deeper interslope divergence in D. simulans than in D. melanogaster, with extensive signatures of selective sweeps present in flies from both slopes but enhanced in the population from the hotter and drier south-facing slope. Interslope divergence was enriched for genes related to electrochemical balance and transmembrane transport, likely in response to increased selection for dehydration resistance on the hotter slope. Both species shared genomic regions that underwent major selective sweeps, but the overall level of adaptive convergence was low, demonstrating no shortage of alternative genomic solutions to cope with the challenges of the microclimate contrast. Mobile elements were a major source of genetic polymorphism and divergence, affecting all parts of the genome, including coding sequences of mating behavior-related genes.
  • Campylobacter jejuni - An emerging foodborne pathogen
    Altekruse, Sean Fitzgerald; Stern, N. J.; Fields, P. I.; Swerdlow, David L. (1999-01)
    Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection-Guillain-Barre syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain.
  • Evaluation of Risk of Zoonotic Pathogen Transmission in a University-Based Animal Assisted Intervention (AAI) Program
    Boyle, Sara F.; Corrigan, Virginia Kiefer; Buechner-Maxwell, Virginia A.; Pierce, Bess J. (Frontiers, 2019-06-04)
    Introduction: Previous studies have shown that apparently healthy animals participating in Animal-Assisted Interventions (AAI) have the potential to asymptomatically carry and even transmit zoonotic pathogens to people, which is of particular concern for therapy animal teams visiting healthcare settings. This two-part study was designed to investigate the risk of zoonotic pathogen transmission within a university-based AAI program as a combination of the prevalence of these pathogens in the animal population as well as the handlers’ understanding of the risks of zoonoses in AAI and their adherence to infection control practices. Methods: In part one of the study, AAI program records were retrospectively reviewed and infectious disease screening test results were compiled from 22 dogs and 2 cats. Screening tests for dogs and cats included a zinc sulfate fecal float, fecal culture, and nasal and perianal skin swabs for methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudointermedius (MRSP). Additional tests for cats were blood cultures for Bartonella henselae and Toxoplasmosis IgG and IgM antibody titers. In part two, a survey was conducted of 40 registered therapy animal handlers to assess knowledge, attitudes, and perceptions regarding risk of infectious disease transmission in AAI settings, including risk to the animal, the handler, and those being visited. Results: In part one, there were 17 total positive results of the 118 infectious disease screenings performed, 14 of which were potentially zoonotic organisms. In part two of the study, a majority (70%) of respondents expressed they had no concerns regarding infectious disease transmission in AAI settings. Despite handler education and guidelines, adherence to infection control practices was lacking. Discussion: The results of this study support prior findings that animals participating in AAI can be asymptomatic carriers of zoonotic organisms. Compliance with infection control practices and hand hygiene are paramount to mitigate risk of zoonotic disease transmission, but was inconsistent among this group of handlers. Given the popularity of AAI programs in the U.S., similar studies should be performed on a larger scale to determine the level of adherence to currently recommended practices and potential need for improvement in infectious disease control education and/or policies.
  • Mapping the potential use of endectocide-treated cattle to reduce malaria transmission
    Imbahale, Susan S.; Montana Lopez, Julia; Brew, Joe; Paaijmansz, Krijn; Rist, Cassidy; Chaccour, Carlos J. (Springer Nature, 2019-04-09)
    Treating cattle with endectocide is a longstanding veterinary practice to reduce the load of endo and ectoparasites, but has the potential to be added to the malaria control and elimination toolbox, as it also kills malaria mosquitoes feeding on the animals. Here we used openly available data to map the areas of the African continent where high malaria prevalence in 2-10 year old children coincides with a high density of cattle and high density of the partly zoophilic malaria vector Anopheles arabiensis. That is, mapping the areas where treating cattle with endectocide would potentially have the greatest impact on reducing malaria transmission. In regions of Africa that are not dominated by rainforest nor desert, the map shows a scatter of areas in several countries where this intervention shows potential, including central and eastern sub-Saharan Africa. The savanna region underneath the Sahel in West Africa appears as the climatic block that would benefit to the largest extent from this intervention, encompassing several countries. West Africa currently presents the highest under-10 malaria prevalence and elimination within the next twenty years cannot be contemplated there with currently available interventions alone, making the use of endectocide treated cattle as a complementary intervention highly appealing.
  • Pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota
    Mu, Qinghui; Cabana-Puig, Xavier; Mao, Jiangdi; Swartwout, Brianna K.; Abdelhamid, Leila; Cecere, Thomas E.; Wang, Haifeng; Reilly, Christopher M.; Luo, Xin M. (2019-07-16)
    Background Dysbiosis of gut microbiota exists in the pathogenesis of many autoimmune diseases, including systemic lupus erythematosus (lupus). Lupus patients who experienced pregnancy usually had more severe disease flares post-delivery. However, the possible role of gut microbiota in the link between pregnancy and exacerbation of lupus remains to be explored. Results In the classical lupus mouse model MRL/lpr, we compared the structures of gut microbiota in pregnant and lactating individuals vs. age-matched naïve mice. Consistent with studies on non-lupus mice, both pregnancy and lactation significantly changed the composition and diversity of gut microbiota. Strikingly, modulation of gut microbiota using the same strategy resulted in different disease outcomes in postpartum (abbreviated as “PP,” meaning that the mice had undergone pregnancy and lactation) vs. control (naïve; i.e., without pregnancy or lactation) MRL/lpr females; while vancomycin treatment attenuated lupus in naïve mice, it did not do so, or even exacerbated lupus, in PP mice. Lactobacillus animalis flourished in the gut upon vancomycin treatment, and direct administration of L. animalis via oral gavage recapitulated the differential effects of vancomycin in PP vs. control mice. An enzyme called indoleamine 2,3-dioxygenase was significantly inhibited by L. animalis; however, this inhibition was only apparent in PP mice, which explained, at least partially, the lack of beneficial response to vancomycin in these mice. The differential production of immunosuppressive IL-10 and proinflammatory IFNγ in PP vs. control mice further explained why the disease phenotypes varied between the two types of mice bearing the same gut microbiota remodeling strategy. Conclusions These results suggest that pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota. Further studies are necessary to better understand the complex relationship between pregnancy and lupus.
  • Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review
    Tham, Heng L.; Linder, Keith E.; Olivry, Thierry (2019-07-19)
    Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes. In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans. Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.
  • Reflective Roofing Research: Influence of Roof Color on Adjacent Air and Surface Temperatures
    Grant, Elizabeth J.; Black, Kenneth Allan; Werre, Stephen R. (2017-03-19)
    An experimental study was conducted to answer questions about the thermal effects of roof reflectivity on the neighbouring built environment. Temperatures were recorded at the surface of black ethylene propylene diene monomer (EPDM) and white thermoplastic polyolefin (TPO) membrane overlay areas; in the air and at electrical metallic tubing (EMT) above them; and at opaque and glazed wall surfaces adjacent to them. The surface of the EPDM roof was significantly hotter than the TPO roof by 36°C and 26°C on two test dates. Air temperatures were 2°C higher above EPDM versus TPO up to 14 cm, with no significant differences above this height. Temperatures were 2°C higher at EMT above the TPO surface than above the EPDM. A precast concrete panel wall was 3°C to 5°C warmer adjacent to TPO versus EPDM. Exterior glazing surface temperatures were 2°C warmer adjacent to TPO versus EPDM.
  • Non-controlled, open-label clinical trial to assess the effectiveness of a dietetic food on pruritus and dermatologic scoring in atopic dogs
    Witzel-Rollins, Angela; Murphy, Maryanne; Becvarova, Iveta; Werre, Stephen R.; Cadiergues, Marie-Christine; Meyer, Hein (2019-06-28)
    Background Canine atopic dermatitis (AD) is a common skin disease. The goal of this study was to evaluate food designed to improve skin barrier function and lower inflammation to reduce pruritus and clinical severity in client-owned atopic dogs. The food contained an antioxidant blend to reduce oxidative stress, plant polyphenols to stabilize mast cells, and polyunsaturated fatty acids to improve skin health and reduce inflammation. Results Seventeen dogs were included in the analysis. Initially 48 adult atopic dogs were enrolled and exclusively fed a dermatologic food for 8 weeks in a non-controlled, open-label study. Thirty-one dogs were excluded for the following reasons: oral and topical medication changes (n = 17), missing data (n = 4), fatty acid supplementation (n = 3), food refusal (n = 3), dropped out (n = 3), and owner concerns (n = 1). Using a scale from 0 (normal) - 4 (severe), veterinarians evaluated the presence and severity of clinical signs of atopy at weeks 0, 4, and 8. Pet owners also rated their pet’s clinical signs of atopy on a scale from 0 (not present) - 10 (present continuously) at weeks 0, 4, and 8. Compared with initial baseline scores (median 19, range 3–69), the total veterinarian scores were significantly lower at weeks 4 (median 11, range 1–15) and 8 (median 7, range 3–46) (p < 0.05). Similarly, owner assessments showed significant improvements in the least squares mean (LSM) from baseline to 4 weeks (itching, redness, licking, and scratching) continuing to 8 weeks (itching, redness, and scratching) (p < 0.05). Conclusions In this open, non-controlled study evaluating a dermatologic diet in seventeen client-owned dogs, owner and veterinarian assessments showed statistically significant reductions in clinical scores designed to measure severity of atopic dermatitis. While these results show promise for the management of canine atopic dermatitis, controlled clinical trials are also needed to affirm our findings.
  • Characterization of Outer Membrane Vesicles from Brucella melitensis and Protection Induced in Mice
    Avila-Calderon, Eric Daniel; Lopez-Merino, Ahidé; Jain, Neeta; Peralta, Humberto; Lopez-Villegas, Edgar Oliver; Sriranganathan, Nammalwar; Boyle, Stephen M.; Witonsky, Sharon G.; Contreras-Rodriguez, Araceli (Hindawi Publishing Corp, 2011-12-29)
    The outer membrane vesicles (OMVs) from smooth B. melitensis 16 M and a derived rough mutant, VTRM1 strain, were purified and characterized with respect to protein content and induction of immune responses in mice. Proteomic analysis showed 29 proteins present in OMVs from B. melitensis 16 M; some of them are well-known Brucella immunogens such as SOD, GroES, Omp31, Omp25, Omp19, bp26, and Omp16. OMVs from a rough VTRM1 induced significantly higher expression of IL-12, TNFa, and IFN? genes in bone marrow dendritic cells than OMVs from smooth strain 16 M. Relative to saline control group, mice immunized intramuscularly with rough and smooth OMVs were protected from challenge with virulent strain B. melitensis 16 M just as well as the group immunized with live strain B. melitensis Rev1 (P < 0.005). Additionally, the levels of serum IgG2a increased in mice vaccinated with OMVs from rough strain VTRM1 consistent with the induction of cell-mediated immunity.
  • Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway
    Wattam, Alice R.; Inzana, Thomas J.; Williams, Kelly P.; Mane, Shrinivasrao P.; Shukla, Maulik; Almeida, Nalvo F.; Dickerman, Allan W.; Mason, Steven; Moriyon, Ignacio; O'Callaghan, David; Whatmore, Adrian M.; Sobral, Bruno; Tiller, Rebekah V.; Hoffmaster, Alex R.; Frace, Michael A.; De Castro, Cristina; Molinaro, Antonio; Boyle, Stephen M.; De, Barun K.; Setubal, Joao C. (American Society for Microbiology, 2012-11)
    Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced Brucella spp. Several important differences were noted. Both BO1T and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of N-formyl-perosamine. While BO1T maintained the genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the wbk region involved in O-antigen synthesis in classic smooth Brucella spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the Brucella species described thus far. IMPORTANCE This report examines differences between genomes from four new Brucella strains and those from the classic Brucella spp. Our results show that the four new strains are outliers with respect to the previously known Brucella strains and yet are part of the genus, forming two new clades. The analysis revealed important information about the evolution and survival mechanisms of Brucella species, helping reshape our knowledge of this important zoonotic pathogen. One discovery of special importance is that one of the strains, BO2, produces an O-antigen distinct from any that has been seen in any other Brucella isolates to date.
  • PATRIC: The VBI PathoSystems Resource Integration Center
    Snyder, E. E.; Kampanya, N.; Lu, J.; Nordberg, E. K.; Karur, H. R.; Shukla, Maulik; Soneja, J.; Tian, Y.; Xue, T.; Yoo, H.; Zhang, F.; Dharmanolla, C.; Dongre, N. V.; Gillespie, J. J.; Hamelius, J.; Hance, M.; Huntington, K. I.; Jukneliene, D.; Koziski, J.; Mackasmiel, L.; Mane, S. P.; Nguyen, V.; Purkayastha, A.; Shallom, J.; Yu, G.; Guo, Y.; Gabbard, Joseph L.; Hix, D.; Azad, A. F.; Baker, S. C.; Boyle, S. M.; Khudyakov, Y.; Meng, Xiang-Jin; Rupprecht, C.; Vinje, J.; Crasta, Oswald R.; Czar, M. J.; Dickerman, Allan W.; Eckart, J. D.; Kenyon, R.; Will, R.; Setubal, Joao C.; Sobral, Bruno (2007-01)
    The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website ( will continually grow with the addition of data, analysis and functionality over the course of the project.
  • A versatile computational pipeline for bacterial genome annotation improvement and comparative analysis, with Brucella as a use case
    Yu, G. X.; Snyder, E. E.; Boyle, S. M.; Crasta, Oswald R.; Czar, M. J.; Mane, S. P.; Purkayastha, A.; Sobral, Bruno; Setubal, Joao C. (2007-06)
    We present a bacterial genome computational analysis pipeline, called GenVar. The pipeline, based on the program GeneWise, is designed to analyze an annotated genome and automatically identify missed gene calls and sequence variants such as genes with disrupted reading frames (split genes) and those with insertions and deletions (indels). For a given genome to be analyzed, GenVar relies on a database containing closely related genomes (such as other species or strains) as well as a few additional reference genomes. GenVar also helps identify gene disruptions probably caused by sequencing errors. We exemplify GenVar's capabilities by presenting results from the analysis of four Brucella genomes. Brucella is an important human pathogen and zoonotic agent. The analysis revealed hundreds of missed gene calls, new split genes and indels, several of which are species specific and hence provide valuable clues to the understanding of the genome basis of Brucella pathogenicity and host specificity.
  • CAGm: A repository of germline microsatellite variations in the 1000 genomes project
    Kinney, N.; Titus-Glover, K.; Wren, J.D.; Varghese, Ronnie; Michalak, Pawel; Liao, H.; Anandakrishnan, Ramu; Pulenthiran, A.; Kang, L.; Garner, Harold R. (Oxford University Press, 2019-01-08)
    The human genome harbors an abundance of repetitive DNA; however, its function continues to be debated. Microsatellites-a class of short tandem repeat-are established as an important source of genetic variation. Array length variants are common among microsatellites and affect gene expression; but, efforts to understand the role and diversity of microsatellite variation has been hampered by several challenges. Without adequate depth, both long-read and short-read sequencing may not detect the variants present in a sample; additionally, large sample sizes are needed to reveal the degree of population-level polymorphism. To address these challenges we present the Comparative Analysis of Germline Microsatellites (CAGm): A database of germline microsatellites from 2529 individuals in the 1000 genomes project. A key novelty of CAGm is the ability to aggregate microsatellite variation by population, ethnicity (super population) and gender. The database provides advanced searching for microsatellites embedded in genes and functional elements. All data can be downloaded as Microsoft Excel spreadsheets. Two use-case scenarios are presented to demonstrate its utility: A mononucleotide (A) microsatellite at the BAT-26 locus and a dinucleotide (CA) microsatellite in the coding region of FGFRL1. CAGm is freely available at © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.
  • Infectious genomic DNA clone and serological profile of torque teno sus virus 1 and 2
    (United States Patent and Trademark Office, 2018-09-04)
    The present invention also provides infectious DNA clones, biologically functional plasmid or viral vector containing the infectious nucleic acid genome molecule of Torque teno sus virus (TTsuV). The present invention also provides methods for diagnosing TTsuV infection via immunological methods, e.g., enzyme-linked immunoabsorbent assay (ELISA) and Western blot using PTTV specific antigens for detecting serum PTTV specific antibodies which indicate infections TTsuV1, TTsuV2, and individual TTsuV1 genotypes.