scholarly journals Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides

2020 ◽  
Vol 62 (1) ◽  
Author(s):  
Flavio Sacchini ◽  
Anne Mariana Liljander ◽  
Martin Heller ◽  
Elizabeth Jane Poole ◽  
Horst Posthaus ◽  
...  
Keyword(s):  
Post Infection ◽  
Close Contact ◽  
Contagious Bovine Pleuropneumonia ◽  
Adult Cattle ◽  
Field Situation ◽  
Successful Infection ◽  
Colony Forming Units ◽  
Infection Models ◽  
Mycoplasma Mycoides ◽  
Current Infection

AbstractContagious bovine pleuropneumonia (CBPP) is a respiratory disease caused by Mycoplasma mycoides subsp. mycoides. Infection occurs via Mycoplasma-containing droplets and therefore requires close contact between animals. The current infection models are suboptimal and based on intratracheal installation of mycoplasmas or in-contact infection. This work tested the infection of adult cattle via aerosols containing live mycoplasmas mimicking the infection of cattle in the field. Therefore, we infected six cattle with aerosolized Mycoplasma mycoides subsp. mycoides strain Afadé over seven consecutive days with altogether 109 colony forming units. All animals seroconverted between 11–24 days post infection and five out of six animals showed typical CBPP lesions. One animal did not show any lung lesions at necropsy, while another animal had to be euthanized at 25 days post infection because it reached endpoint criteria. Seroconversion confirmed successful infection and the spectrum of clinical and lesions observed mirrors epidemiological models and the field situation, in which only a fraction of animals suffers from acute clinical disease post infection.

scholarly journals Observations on experimental inactivated vaccines for contagious bovine pleuropneumonia

1986 ◽  
Vol 97 (2) ◽  
pp. 305-315 ◽  
Author(s):  
M. A. Gray ◽  
P. Simam ◽  
G. R. Smith
Keyword(s):  
Small Dose ◽  
Close Contact ◽  
Contagious Bovine Pleuropneumonia ◽  
Complete Protection ◽  
Freund’S Complete Adjuvant ◽  
Extreme Form ◽  
Protective Antibody ◽  
Freund's Complete Adjuvant ◽  
Mycoplasma Mycoides ◽  
Inactivated Vaccines

SummaryIn two trials the efficacy of inactivated vaccines against contagious bovine pleuropneumonia was tested by exposing vaccinated cattle to droplet infection provided by close contact with experimentally infected ‘donors’. Complete protection was given by an extreme form of vaccination in which a heavy suspension of killed Mycoplasma mycoides subsp. mycoides emulsified with Freund's complete adjuvant was given in two large doses. ‘Mouse-protective antibody’ (MPA) was also produced, i.e. serum transferred to mice 2–4 h before intraperitoneal challenge prevented the development of mycoplasmaemia. However, the study did not answer the question ‘Is MPA protective for cattle?’. No protection was given by a milder form of vaccination in which a lighter suspension of killed Hiycoplasmas emulsified with Freund's incomplete adjuvant was given in a comparatively small dose on a single occasion.

scholarly journals Cytotoxicity of Mycoplasma mycoides subsp. mycoides Small Colony Type to Bovine Epithelial Cells

2007 ◽  
Vol 76 (1) ◽  
pp. 263-269 ◽  
Author(s):  
Daniela F. Bischof ◽  
Carole Janis ◽  
Edy M. Vilei ◽  
Giuseppe Bertoni ◽  
Joachim Frey
Keyword(s):  
Close Contact ◽  
Clinical Signs ◽  
Host Cells ◽  
Uptake System ◽  
Contagious Bovine Pleuropneumonia ◽  
Colony Type ◽  
Mycoplasma Mycoides ◽  
Small Colony ◽  
High Cytotoxicity

ABSTRACT The cytotoxicities of various strains of Mycoplasma mycoides subsp. mycoides small colony type (SC), the agent of contagious bovine pleuropneumonia (CBPP), were measured in vitro using embryonic calf nasal epithelial (ECaNEp) cells. Strains isolated from acute cases of CBPP induced high cytotoxicity in the presence of glycerol, concomitant with the release of large amounts of toxic H2O2 that were found to be translocated into the cytoplasms of the host cells by close contact of the Mycoplasma strains with the host cells. Currently used vaccine strains also showed high cytotoxicity and high H2O2 release, indicating that they are attenuated in another virulence attribute. Strains isolated from recent European outbreaks of CBPP with mild clinical signs, which are characterized by a defect in the glycerol uptake system, released small amounts of H2O2 and showed low cytotoxicity to ECaNEp cells. M. mycoides subsp. mycoides SC strain PG1 released large amounts of H2O2 but was only slightly cytotoxic. PG1 was found to have a reduced capacity to bind to ECaNEp cells and was unable to translocate H2O2 into the bovine cells, in contrast to virulent strains that release large amounts of H2O2. Thus, an efficient translocation of H2O2 into host cells is a prerequisite for the cytotoxic effect and requires an intact adhesion mechanism to ensure a close contact between mycoplasmas and host cells.

scholarly journals 707. QPX9003: Pharmacology of a Novel Polymyxin in Mice and Rats

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S319-S319
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
Jonathan Parkinson ◽  
Kade Roberts ◽  
Philip Thompson ◽  
...  
Keyword(s):  
Post Infection ◽  
Lethal Dose ◽  
Lung Infection ◽  
Infection Model ◽  
Rat Lung ◽  
Sprague Dawley ◽  
Bacterial Killing ◽  
Swiss Mice ◽  
Infection Models

Abstract Background Currently available polymyxins are limited by toxicity and poor efficacy at tolerated doses. We have developed a new series of polymyxin derivatives with improved safety profiles and in vitro potency against major MDR bacteria. The following describes studies on the in vivo antimicrobial activity and toxicity of QPX9003 in mice and rats. Methods Mouse studies. The minimum lethal dose (MLD by IV bolus) and nephrotoxicity (6 IP doses administered 2 hours apart) of QPX9003 and polymyxin B (PMB) were determined in Swiss mice. For the neutropenic mouse thigh infection using A. baumannii, Swiss mice were infected with ~106 CFU/thigh. Doses were administered IP at various intervals starting 2-hour post-infection and continued over 24 hours. Rat studies. For the rat lung infection model, Sprague-Dawley rats were infected with ~107 CFU/lung. QPX9003 and PMB were administered IV every 4 hours starting 2 hours post-infection and continued over 24 hours. Bacteria. For both infection models, animals were infected with A. baumannii AB1016 (QPX9003 MIC of 0.5 mg/L and PMB MIC of 1.0 mg/L). Untreated control groups were sacrificed at the start of treatment and both untreated and treated groups were sacrificed 24 hours after the start of treatment, infected tissues harvested, homogenized, and plated to determine colony counts. Results QPX9003 had reduced acute toxicity and nephrotoxicity compared with PMB in mice. QPX9003 showed better bacterial killing of A. baumannii than PMB at similar plasma exposures in both the mouse thigh model (−0.41 vs. +0.83 log CFU/thigh) and rat lung infection model (−1.10 vs. +1.44 log CFU/lung). Conclusion QPX9003 was less acutely toxic, less nephrotoxic, and was more efficacious in mouse and rat infection models compared with PMB. QPX9003 is a promising new polymyxin. (This work was supported in part by federal funds from the National Institutes of Allergy and Infectious Diseases [R01AI098771], and the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under OTA number HHSO100201600026C). Disclosures All authors: No reported disclosures.

scholarly journals 1560. Pharmacokinetics–Pharmacodynamics (PK-PD) of Gepotidacin (GEP) Against Escherichia coli in Murine Pyelonephritis and Thigh Infection Models

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S569-S569
Author(s):  
Aline Barth ◽  
Cindy l Mininger ◽  
Thomas Lewandowski ◽  
Mohammad Hossain ◽  
Stephen Rittenhouse ◽  
...  
Keyword(s):  
Post Infection ◽  
Tissue Samples ◽  
Acute Cystitis ◽  
E Coli ◽  
Poppk Model ◽  
Infection Models ◽  
Median Plasma ◽  
Bacterial Replication ◽  
Parameter Values

Abstract Background GEP, a first in class novel triazaacenaphthylene bacterial topoisomerase inhibitor, inhibits bacterial replication and has in vitro activity against key pathogens implicated in a range of infections, including drug-resistant strains of E. coli associated with acute cystitis. Methods PK and PD studies were conducted in murine (male CD-1 mice) thigh and kidney infections. The administered doses ranged from 1 to 200 mg/kg SC every 6 hours starting 1-hour post-infection. Infected tissues were evaluated for bacterial burden at 24-h post-infection (baseline controls at 1-hour post-infection). Plasma and tissue samples (kidney or thigh homogenates) were collected at 15, 30, 60, 120, 240 and 360 minutes. A population PK (PopPK) model was built in NONMEM using plasma exposures. Efficacy was determined against E. coli ALL, 997577, ATCC25922, IR5 and NCTC13441 (MICs of 1 to 4 µg/mL) in thigh-infected neutropenic (I-) mice and against E. coli ALL in kidney-infected immunocompetent (I+) and I- mice. The PopPK model was used to determine GEP exposures associated with efficacy. PK-PD analyses were conducted using Phoenix WinNonLin 6.3 (Pharsight). The change in log10 colony-forming units (CFU) from baseline were correlated with free drug (f) AUC:MIC using an inhibitory model from the Phoenix library, and model parameter values for each isolate were used to calculate the plasma fAUC:MIC associated with stasis, 1- or 2-log10 reductions in CFU. Results Plasma PK data were best fit by a 1-compartment IV model with first-order elimination and were similar in I+ vs. I- and thigh- vs. kidney-infected mice. The AUC0-6 of GEP in kidney was approximately 4- to 5-fold higher than in plasma while the AUC0-6 in thigh was approximately half of plasma. In the I- thigh model, median plasma fAUC:MIC ratios for stasis, 1- or 2-log10 reductions in CFU were 11, 16, and 25 (ranges 3–17, 4–25 and 7–40), respectively. Efficacy vs. E. coli ALL was similar in I- mice infected in thigh or kidney. In I+ mice, the PK-PD target was reduced by half. Conclusion Median plasma fAUC:MIC targets ranged from 11 to 25. Higher drug levels in kidney vs. plasma or thigh did not translate into improved efficacy in pyelonephritis vs. thigh-infection models. Disclosures All authors: No reported disclosures.

A simplified PCR method for genotyping Mycoplasma mycoides subspecies mycoides small colony: The aetiologic agent of contagious bovine pleuropneumonia

2012 ◽  
Vol 159 (1-2) ◽  
pp. 257-259
Author(s):  
Colin P. Churchward ◽  
Miroslav Hlúšek ◽  
Robin A.J. Nicholas ◽  
Roger D. Ayling ◽  
Laura McAuliffe
Keyword(s):  
Contagious Bovine Pleuropneumonia ◽  
Mycoplasma Mycoides ◽  
Small Colony ◽  
Pcr Method

scholarly journals Development of a Novel Cocktail Enzyme-Linked Immunosorbent Assay and a Field-Applicable Lateral-Flow Rapid Test for Diagnosis of Contagious Bovine Pleuropneumonia

2016 ◽  
Vol 54 (6) ◽  
pp. 1557-1565 ◽  
Author(s):  
Martin Heller ◽  
Nimmo Gicheru ◽  
Georgina Tjipura-Zaire ◽  
Cecilia Muriuki ◽  
Mingyan Yu ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Rapid Test ◽  
Lateral Flow ◽  
Sub Saharan Africa ◽  
Enzyme Linked Immunosorbent Assay ◽  
Contagious Bovine Pleuropneumonia ◽  
Serum Samples ◽  
Content Type ◽  
Mycoplasma Mycoides ◽  
Sub Saharan

Contagious bovine pleuropneumonia (CBPP) is a severe respiratory disease that is widespread in sub-Saharan Africa. It is caused byMycoplasma mycoidessubsp.mycoides, a bacterium belonging to theMycoplasma mycoidescluster. In the absence of an efficient CBPP vaccine, improved and easy-to-use diagnostic assays for recurrent testing combined with isolation and treatment of positive animals represent an option for CBPP control in Africa. Here we describe the comprehensive screening of 17 immunogenicMycoplasma mycoidessubsp.mycoidesproteins using well-characterized bovine sera for the development of a novel cocktail enzyme-linked immunosorbent assay (ELISA) for laboratory use. Two recombinantMycoplasmaimmunogens, MSC_0136 and MSC_0636, were used to set up a standardized cocktail ELISA protocol. According to the results from more than 100 serum samples tested, the sensitivity and specificity of the novel cocktail ELISA were 85.6% and 96.4%, respectively, with an overall diagnostic accuracy comparable to that of the Office International des Epizooties (OIE)-prescribed serological assays. In addition, we provide a proof of principle for a field-applicable, easy-to-use commercially produced prototype lateral-flow test for rapid (<30-min) diagnosis of CBPP.

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