Comparison of virulence of different Actinobacillus pleuropneumoniae serotypes and biotypes using an aerosol infection model

1996 ◽  
Vol 49 (3-4) ◽  
pp. 159-168 ◽  
Author(s):  
Mariann Juul Jacobsen ◽  
Jens Peter Nielsen ◽  
Ragnhild Nielsen
Keyword(s):  
Actinobacillus Pleuropneumoniae ◽  
Infection Model ◽  
Aerosol Infection

scholarly journals Deletion of the Ferric Uptake Regulator Fur Impairs the In Vitro Growth and Virulence of Actinobacillus pleuropneumoniae

2005 ◽  
Vol 73 (6) ◽  
pp. 3740-3744 ◽  
Author(s):  
Ilse Jacobsen ◽  
Jörg Gerstenberger ◽  
Achim D. Gruber ◽  
Janine T. Bossé ◽  
Paul R. Langford ◽  
...  
Keyword(s):  
Deletion Mutant ◽  
Constitutive Expression ◽  
Actinobacillus Pleuropneumoniae ◽  
Infection Model ◽  
Ferric Uptake Regulator ◽  
In Vitro Growth ◽  
Transferrin Binding Proteins ◽  
Aerosol Infection

ABSTRACT In order to investigate the role of the ferric uptake regulator Fur in the porcine lung pathogen Actinobacillus pleuropneumoniae, we constructed an isogenic in-frame deletion mutant, A. pleuropneumoniae Δfur. This mutant showed constitutive expression of transferrin-binding proteins, growth deficiencies in vitro, and reduced virulence in an aerosol infection model.

scholarly journals Enzymes Involved in Anaerobic Respiration Appear To Play a Role in Actinobacillus pleuropneumoniae Virulence

2005 ◽  
Vol 73 (1) ◽  
pp. 226-234 ◽  
Author(s):  
Ilse Jacobsen ◽  
Isabel Hennig-Pauka ◽  
Nina Baltes ◽  
Matthias Trost ◽  
Gerald-F. Gerlach
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Anaerobic Respiration ◽  
Clinical Score ◽  
Lavage Fluid ◽  
Actinobacillus Pleuropneumoniae ◽  
Lung Lesion ◽  
Infection Model ◽  
Binding Motif ◽  
Anaerobic Conditions

ABSTRACT Actinobacillus pleuropneumoniae, the etiological agent of porcine pleuropneumonia, is able to survive on respiratory epithelia, in tonsils, and in the anaerobic environment of encapsulated sequesters. It was previously demonstrated that a deletion of the anaerobic dimethyl sulfoxide reductase gene (dmsA) results in attenuation in acute disease (N. Baltes, S. Kyaw, I. Hennig-Pauka, and G. F. Gerlach, Infect. Immun. 71:6784-6792, 2003). In the present study, using two-dimensional polyacrylamide gel electrophoresis and quadrupole time-of-flight mass spectrometry, we identified an aspartate ammonia-lyase (AspA) which is upregulated upon induction with bronchoalveolar lavage fluid (BALF). This enzyme is involved in the production of fumarate, an alternative electron acceptor under anaerobic conditions. The coding gene (aspA) was cloned and shown to be present in all A. pleuropneumoniae serotype reference strains. The transcriptional start point was identified downstream of a putative FNR binding motif, and BALF-dependent activation of aspA was confirmed by construction of an isogenic A. pleuropneumoniae mutant carrying a chromosomal aspA::luxAB transcriptional fusion. Two aspA deletion mutants, A. pleuropneumoniae ΔaspA and A. pleuropneumoniae ΔaspAΔdmsA, were constructed, both showing reduced growth under anaerobic conditions in vitro. Pigs challenged with either of the two mutants in an aerosol infection model showed a lower lung lesion score than that of the A. pleuropneumoniae wild-type (wt) controls. Pigs challenged with A. pleuropneumoniae ΔaspAΔdmsA had a significantly lower clinical score, and this mutant was rarely reisolated from unaltered lung tissue; in contrast, A. pleuropneumoniae ΔaspA and the A. pleuropneumoniae wt were consistently reisolated in high numbers. These results suggest that enzymes involved in anaerobic respiration are necessary for the pathogen's ability to persist on respiratory tract epithelium and play an important role in A. pleuropneumoniae pathogenesis.

Establishment and comparison of Actinobacillus pleuropneumoniae experimental infection model in mice and piglets

2019 ◽  
Vol 128 ◽  
pp. 381-389 ◽  
Author(s):  
Chun-tong Bao ◽  
Jia-meng Xiao ◽  
Bai-jun Liu ◽  
Jian-fang Liu ◽  
Ri-ning Zhu ◽  
...  
Keyword(s):  
Experimental Infection ◽  
Actinobacillus Pleuropneumoniae ◽  
Infection Model ◽  
Experimental Infection Model

scholarly journals Pulmonary Necrosis Resulting from DNA Vaccination against Tuberculosis

2003 ◽  
Vol 71 (4) ◽  
pp. 2192-2198 ◽  
Author(s):  
Jennifer L. Taylor ◽  
Oliver C. Turner ◽  
Randall J. Basaraba ◽  
John T. Belisle ◽  
Kris Huygen ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Vaccine ◽  
Latent Tuberculosis ◽  
Mycobacterium Leprae ◽  
Dna Vaccination ◽  
Infection Model ◽  
New Approach ◽  
Dna Coding ◽  
Cellular Necrosis ◽  
Aerosol Infection

ABSTRACT The use of DNA constructs encoding mycobacterial proteins is a promising new approach to vaccination against tuberculosis. A DNA vaccine encoding the hsp60 molecule of Mycobacterium leprae has previously been shown to protect against intravenous infection of mice with Mycobacterium tuberculosis in both the prophylactic and immunotherapeutic modes. It is shown here, however, that this vaccine was not effective in a more realistic aerosol infection model or in a model of latent tuberculosis in the lungs. Moreover, when given in an immunotherapeutic model the immunized mice developed classical Koch reactions characterized by multifocal discrete regions of cellular necrosis throughout the lung granulomas. Similar and equally severe reactions were seen in mice given a vaccine with DNA coding for the Ag85 antigen of M. tuberculosis. This previously unanticipated safety problem indicates that DNA vaccines should be used with caution in individuals who may have already been exposed to tuberculosis.

Pharmacokinetic/pharmacodynamic assessment of cefquinome against Actinobacillus Pleuropneumoniae in a piglet tissue cage infection model

2018 ◽  
Vol 219 ◽  
pp. 100-106 ◽  
Author(s):  
Longfei Zhang ◽  
Xun Wu ◽  
Zilong Huang ◽  
Nan Zhang ◽  
Yuzhi Wu ◽  
...  
Keyword(s):  
Actinobacillus Pleuropneumoniae ◽  
Infection Model

scholarly journals Effect of Coadministration of Moxifloxacin and Rifampin on Mycobacterium tuberculosis in a Murine Aerosol Infection Model

2012 ◽  
Vol 56 (6) ◽  
pp. 3054-3057 ◽  
Author(s):  
V. Balasubramanian ◽  
S. Solapure ◽  
S. Gaonkar ◽  
K. N. Mahesh Kumar ◽  
R. K. Shandil ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hollow Fiber ◽  
Lung Model ◽  
Control Group ◽  
Infection Model ◽  
Content Type ◽  
Days Of Therapy ◽  
Cell Kill ◽  
Aerosol Infection

ABSTRACTCoadministration of moxifloxacin and rifampin was evaluated in a murine model ofMycobacterium tuberculosispulmonary infection to determine whether the finding of antagonism documented in a hollow-fiber infection model could be recapitulatedin vivo. Colony counts were followed in a no-treatment control group, groups administered moxifloxacin or rifampin monotherapy, and a group administered a combination of the two agents. Following 18 days of once-daily oral administration to mice infected withM. tuberculosis, there was a reduction in the plasma exposure to rifampin that decreased further when rifampin was coadministered with moxifloxacin. Pharmacodynamic analysis demonstrated a mild antagonistic interaction between moxifloxacin and rifampin with respect to cell kill in the mouse model for tuberculosis (TB). No emergence of resistance was noted over 28 days of therapy, even with monotherapy. This was true even though one of the agents in the combination (moxifloxacin) induces error-prone replication. The previously noted antagonism with respect to cell kill shown in the hollow-fiber infection model was recapitulated in the murine TB lung model, although to a lesser extent.

Induction of protective immunity by aerosol or oral application of candidate vaccines in a dose-controlled pig aerosol infection model

1996 ◽  
Vol 44 (1-3) ◽  
pp. 171-181 ◽  
Author(s):  
Andreas Hensel ◽  
Leo A.M.G. van Leengoed ◽  
Michael Szostak ◽  
Horst Windt ◽  
Herbert Weissenböck ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Infection Model ◽  
Oral Application ◽  
Aerosol Infection

scholarly journals Comparative Studies Evaluating Mouse Models Used for Efficacy Testing of Experimental Drugs againstMycobacterium tuberculosis

2010 ◽  
Vol 55 (3) ◽  
pp. 1237-1247 ◽  
Author(s):  
Mary A. De Groote ◽  
Janet C. Gilliland ◽  
Colby L. Wells ◽  
Elizabeth J. Brooks ◽  
Lisa K. Woolhiser ◽  
...  
Keyword(s):  
Mouse Models ◽  
Low Dose ◽  
Drug Regimen ◽  
Drug Combinations ◽  
Infection Model ◽  
High Dose ◽  
Standard Drug ◽  
Experimental Drugs ◽  
Infection Models ◽  
Aerosol Infection

ABSTRACTMethodologies for preclinical animal model testing of drugs againstMycobacterium tuberculosisvary from laboratory to laboratory; however, it is unknown if these variations result in different outcomes. Thus, a series of head-to-head comparisons of drug regimens in three commonly used mouse models (intravenous, a low-dose aerosol, and a high-dose aerosol infection model) and in two strains of mice are reported here. Treatment with standard tuberculosis (TB) drugs resulted in similar efficacies in two mouse species after a low-dose aerosol infection. When comparing the three different infection models, the efficacies in mice of rifampin and pyrazinamide were similar when administered with either isoniazid or moxifloxacin. Relapse studies revealed that the standard drug regimen showed a significantly higher relapse rate than the moxifloxacin-containing regimen. In fact, 4 months of the moxifloxacin-containing combination regimen showed similar relapse rates as 6 months of the standard regimen. The intravenous model showed slower bactericidal killing kinetics with the combination regimens tested and a higher relapse of infection than either aerosol infection models. All three models showed similar outcomes forin vivoefficacy and relapse of infection for the drug combinations tested, regardless of the mouse infection model used. Efficacy data for the drug combinations used also showed similar results, regardless of the formulation used for rifampin or timing of the drugs administered in combination. In all three infection models, the dual combination of rifampin and pyrazinamide was less sterilizing than the standard three-drug regimen, and therefore the results do not support the previously reported antagonism between standard TB agents.

scholarly journals IFN-γ-/- mice resist Actinobacillus pleuropneumoniae infection by promoting early lung IL-18 release and PMN-I accumulation

2021 ◽  
Author(s):  
Chuntong Bao ◽  
Baijun Liu ◽  
Rining Zhu ◽  
Jiameng Xiao ◽  
Ziheng Li ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Bacterial Load ◽  
Actinobacillus Pleuropneumoniae ◽  
Infection Model ◽  
Treatment Protocols ◽  
Porcine Pleuropneumonia ◽  
Mouse Infection Model ◽  
Common Infectious Disease ◽  
Ifn Γ

Porcine pleuropneumonia is a common infectious disease of pigs caused by Actinobacillus pleuropneumoniae (APP). IFN-γ expression increases in the lung of pigs after APP infection, but the role of IFN-γ during the infection is still obscure. In this study, an IFN-γ-/- mouse infection model was established, and bacterial load, the levels of inflammatory cytokines and the types of neutrophils in the lungs were studied at different times post APP infection. We found that wild-type (WT) mice were more susceptible to APP than IFN-γ-/- mice. At 6 h post infection (hpi), the expression of IL-18 and IL-1β in the lungs of IFN-γ-/- mice were significantly increased compared to WT mice. The bacterial load and levels of inflammatory cytokines (IL-1β and IL-6) of IFN-γ-/- mice were significantly reduced at 12 hpi compared to WT mice. After an initial loss, the numbers of lung polymorphonuclear (PMN)-I cells dramatically increased in the lungs of IFN-γ-/- but not WT mice, whereas PMN-II cells continually decreased. Finally, in vivo administration of IL-18 significantly reduced clinical scores and bacterial load in the lungs of APP-infected mice. This study identifies IFN-γ as a target for regulating the inflammatory response in the lung, and provides a basis for understanding the course of clinical bacterial pneumonia and for the formulation of treatment protocols.

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