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  1. Article ; Online: Editorial

    Mark Gray / Stefano Guido / Abirami Kugadas

    Frontiers in Veterinary Science, Vol

    The use of large animal models to improve pre-clinical translational research

    2022  Volume 9

    Keywords disease models (animal) ; comparative model ; large animal models ; translational ; genetically altered animals ; Veterinary medicine ; SF600-1100
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities

    Anastasiia Petenkova / Shelby A. Auger / Jeffrey Lamb / Daisy Quellier / Cody Carter / On Tak To / Jelena Milosevic / Rana Barghout / Abirami Kugadas / Xiaoxiao Lu / Jennifer Geddes-McAlister / Raina Fichorova / David B. Sykes / Mark D. Distefano / Mihaela Gadjeva

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 16

    Abstract: Abstract The bactericidal function of neutrophils is dependent on a myriad of intrinsic and extrinsic stimuli. Using systems immunology approaches we identify microbiome- and infection-induced changes in neutrophils. We focus on investigating the ... ...

    Abstract Abstract The bactericidal function of neutrophils is dependent on a myriad of intrinsic and extrinsic stimuli. Using systems immunology approaches we identify microbiome- and infection-induced changes in neutrophils. We focus on investigating the Prenylcysteine oxidase 1 like (Pcyox1l) protein function. Murine and human Pcyox1l proteins share ninety four percent aminoacid homology revealing significant evolutionary conservation and implicating Pcyox1l in mediating important biological functions. Here we show that the loss of Pcyox1l protein results in significant reductions in the mevalonate pathway impacting autophagy and cellular viability under homeostatic conditions. Concurrently, Pcyox1l CRISPRed-out neutrophils exhibit deficient bactericidal properties. Pcyox1l knock-out mice demonstrate significant susceptibility to infection with the gram-negative pathogen Psuedomonas aeruginosa exemplified through increased neutrophil infiltrates, hemorrhaging, and reduced bactericidal functionality. Cumulatively, we ascribe a function to Pcyox1l protein in modulation of the prenylation pathway and suggest connections beween metabolic responses and neutrophil functionality.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: β-Hemolysis May Not Be a Reliable Indicator of Leukotoxicity of Mannheimia haemolytica Isolates

    Jegarubee Bavananthasivam / Sudarvili Shanthalingam / Abirami Kugadas / Bindu Raghavan / Sai Batra / Subramaniam Srikumaran

    Toxins, Vol 10, Iss 5, p

    2018  Volume 173

    Abstract: Mannheimia (Pasteurella) haemolytica causes bronchopneumonia in domestic and wild ruminants. Leukotoxin is the critical virulence factor of M. haemolytica. Since β-hemolysis is caused by a large number of leukotoxin-positive M. haemolytica isolates, all ... ...

    Abstract Mannheimia (Pasteurella) haemolytica causes bronchopneumonia in domestic and wild ruminants. Leukotoxin is the critical virulence factor of M. haemolytica. Since β-hemolysis is caused by a large number of leukotoxin-positive M. haemolytica isolates, all β-hemolytic M. haemolytica isolates are considered to be leukotoxic as well. However, conflicting reports exist in literature as to the leukotoxic and hemolytic properties of M. haemolytica. One group of researchers reported their leukotoxin-deletion mutants to be hemolytic while another reported their mutants to be non-hemolytic. The objective of this study was to determine whether β-hemolysis is a reliable indicator of leukotoxicity of M. haemolytica isolates. Ninety-five isolates of M. haemolytica were first confirmed for presence of leukotoxin gene (lktA) by a leukotoxin-specific PCR assay. Culture supernatant fluids from these isolates were then tested for presence of leukotoxin protein by an ELISA, and for leukotoxic activity by a cytotoxicity assay. All isolates were tested for β-hemolysis by culture on blood agar plates. Sixty-two isolates (65%) produced leukotoxin protein while 33 isolates (35%) did not. Surprisingly, 18 of the 33 isolates (55%), that did not produce leukotoxin protein, were hemolytic. Of the 62 isolates that produced leukotoxin, 55 (89%) were leukotoxic while 7 (11%) were not. All except one of the 55 leukotoxic isolates (98%) were also hemolytic. All seven isolates that were not leukotoxic were hemolytic. Taken together, these results suggest that β-hemolysis may not be a reliable indicator of leukotoxicity of M. haemolytica isolates. Furthermore, all M. haemolytica isolates that possess lktA gene may not secrete active leukotoxin.
    Keywords Mannheimia haemolytica ; leukotoxin ; leukotoxicity ; hemolysis ; indicator ; Medicine ; R
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Effect of vaccination against pneumonia on the survival of bighorn sheep (Ovis canadensis) commingled with carrier animals

    Raghavan, Bindu / Abirami Kugadas / Gary J. Haldorson / Jegarubee Bavananthasivam / Subramaniam Srikumaran

    Veterinary microbiology. 2017 May, v. 203

    2017  

    Abstract: Leukotoxin producing (lkt+) members of Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi are important pathogens of pneumonia in bighorn sheep (BHS; Ovis canadensis), causing fatal disease. Predisposing or concurrent ... ...

    Abstract Leukotoxin producing (lkt+) members of Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi are important pathogens of pneumonia in bighorn sheep (BHS; Ovis canadensis), causing fatal disease. Predisposing or concurrent infection with Mycoplasma ovipneumoniae enhances the severity of the disease, resulting in increased morbidity and mortality. Several studies have investigated the effectiveness of vaccines against lkt+ members of Pasteurellaceae in preventing fatal pneumonia in BHS. In all of these studies, however, vaccinated animals were challenged experimentally, by direct inoculation of the pathogens, rather than by natural challenge. Moreover, none has investigated the efficacy of the vaccines under conditions of concurrent infection with M. ovipneumoniae. We immunized three bighorn rams and one pregnant ewe with an experimental multivalent vaccine along with a commercial vaccine. The immunized animals were then commingled with two bighorn ewes known to be carriers of lkt+ members of Pasteurellaceae, to simulate natural infection or disease transmission. All vaccinated animals remained healthy. We then inoculated the two carrier ewes with nasal washings from domestic sheep containing M. ovipneumoniae. Within a week, all animals developed mild to moderate signs of pneumonia. While the rams died within two-three months post-inoculation (p.i.), the vaccinated ewe and her lamb died five and eight months p.i., respectively. Taken together, these results suggest that vaccination of BHS against lkt+ members of Pasteurellaceae alone can protect them from natural challenge by these pathogens. However, it may not be adequate to protect them against pneumonia compounded by concurrent infection with M. ovipneumoniae.
    Keywords disease transmission ; ewes ; leukotoxins ; Mannheimia haemolytica ; mixed infection ; morbidity ; mortality ; Mycoplasma ovipneumoniae ; nose ; Ovis canadensis ; pathogens ; pneumonia ; rams ; vaccination ; vaccines
    Language English
    Dates of publication 2017-05
    Size p. 56-61.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 753154-0
    ISSN 1873-2542 ; 0378-1135
    ISSN (online) 1873-2542
    ISSN 0378-1135
    DOI 10.1016/j.vetmic.2017.02.013
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Role of carriers in the transmission of pneumonia in bighorn sheep (Ovis canadensis)

    Bindu Raghavan / Kayla Erickson / Abirami Kugadas / Sai A. Batra / Douglas R. Call / Margaret A. Davis / William J. Foreyt / Subramaniam Srikumaran

    Biology Open, Vol 5, Iss 6, Pp 745-

    2016  Volume 755

    Abstract: In the absence of livestock contact, recurring lamb mortality in bighorn sheep (Ovis canadensis) populations previously exposed to pneumonia indicates the likely presence of carriers of pneumonia-causing pathogens, and possibly inadequate maternally ... ...

    Abstract In the absence of livestock contact, recurring lamb mortality in bighorn sheep (Ovis canadensis) populations previously exposed to pneumonia indicates the likely presence of carriers of pneumonia-causing pathogens, and possibly inadequate maternally derived immunity. To investigate this problem we commingled naïve, pregnant ewes (n=3) with previously exposed rams (n=2). Post-commingling, all ewes and lambs born to them acquired pneumonia-causing pathogens (leukotoxin-producing Pasteurellaceae and Mycoplasma ovipneumoniae), with subsequent lamb mortality between 4-9 weeks of age. Infected ewes became carriers for two subsequent years and lambs born to them succumbed to pneumonia. In another experiment, we attempted to suppress the carriage of leukotoxin-producing Pasteurellaceae by administering an antibiotic to carrier ewes, and evaluated lamb survival. Lambs born to both treatment and control ewes (n=4 each) acquired pneumonia and died. Antibody titers against leukotoxin-producing Pasteurellaceae in all eight ewes were ‘protective’ (>1:800 and no apparent respiratory disease); however their lambs were either born with comparatively low titers, or with high (but non-protective) titers that declined rapidly within 2-8 weeks of age, rendering them susceptible to fatal disease. Thus, exposure to pneumonia-causing pathogens from carrier ewes, and inadequate titers of maternally derived protective antibodies, are likely to render bighorn lambs susceptible to fatal pneumonia.
    Keywords Bighorn sheep ; Pneumonia ; Carrier ; Antibodies ; Pasteurellaceae ; Mycoplasma ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2016-06-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis.

    Abirami Kugadas / Stig Hill Christiansen / Saiprasad Sankaranarayanan / Neeraj K Surana / Stefanie Gauguet / Ryan Kunz / Raina Fichorova / Thomas Vorup-Jensen / Mihaela Gadjeva

    PLoS Pathogens, Vol 12, Iss 9, p e

    2016  Volume 1005855

    Abstract: The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular ... ...

    Abstract The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa-induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice that are typically resistant to P. aeruginosa-induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found to be dependent on both eye and gut microbiota with the eye microbiota having a moderate, but significant impact on the resistance to infection. These events were IL-1ß-dependent as corneal IL-1ß levels were decreased in the infected GF and antibiotic-treated mice when compared to the SPF controls, and neutralization of IL-1ß increased the ocular bacterial burden in the SPF mice. Monocolonizing GF mice with Coagulase Negative Staphylococcus sp. isolated from the conjunctival swabs was sufficient to restore resistance to infection. Cumulatively, these data underline a previously unappreciated role for microbiota in regulating susceptibility to ocular keratitis. We predict that these results will have significant implications for contact lens wearers, where alterations in the ocular commensal communities may render the ocular surface vulnerable to infections.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2016-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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