Mycoplasma hyopneumoniae Inhibits Porcine Beta-Defensin 2 Production by Blocking the Unfolded Protein Response To Facilitate Epithelial Adhesion and Infection
INFECTION AND IMMUNITY
Authors: Pan, Qiao; Wang, Xiumei; Liu, Tong; Yu, Ying; Li, Lu; Zhou, Rui; Li, Ganwu; Xin, Jiuqing
Mycoplasma hyopneumoniae causes the disease porcine enzootic pneumonia, a highly contagious and chronic disease affecting pigs. Understanding the molecular mechanisms of its pathogenicity is critical for developing effective interventions to control this swine respiratory disease. Here, we describe a novel virulence mechanism by which M. hyopneumoniae interferes with the host unfolded protein response (UPR) and eventually facilitates bacterial adhesion and infection. We observed that M. hyopneumoniae infection suppressed the UPR target molecules GRP78 and CHOP by reducing PKR-like endoplasmic reticulum kinase/eukaryotic initiation factor 2 alpha (PERK/eIF2 alpha) phosphorylation, ATF6 cleavage, and X-box binding protein 1 (XBP1) splicing. Interestingly, further analyses revealed that host UPR inhibition subsequently suppressed the NF-kappa B pathway, leading to the reduced production of porcine beta-defensin 2 (PBD-2), thus facilitating M. hyopneumoniae adherence and infection. This study provides new insights into the molecular pathogenesis of M. hyopneumoniae and sheds light upon its interactions with the host.
Clinical response to 2 protocols of aerosolized gentamicin in 46 dogs withBordetella bronchisepticainfection (2012-2018)
JOURNAL OF VETERINARY INTERNAL MEDICINE
Authors: Canonne, Aude Morgane; Roels, Elodie; Menard, Maud; Desquilbet, Loic; Billen, Frederic; Clercx, Cecile
Background Bordetella bronchiseptica(Bb) infection commonly causes respiratory disease in dogs. Gentamicin delivered by aerosol maximizes local drug delivery without systemic absorption but clinical response to protocols remains undetermined. Objectives To compare the clinical response to 2 protocols of aerosolized delivery of gentamicin in bordetellosis. Animals Forty-six dogs withBbinfection confirmed by culture or quantitative polymerase chain reaction on bronchoalveolar lavage. Methods Retrospective study. Administration of aerosolized gentamicin for >= 10 minutes q12h for >= 3 weeks using 4 mg/kg diluted with saline (group 1) or undiluted 5% solution (group 2). Clinical response firstly assessed after 3-4 weeks and treatment pursued by 3-weeks increments if cure not reached. Cure defined as absence of cough persisting at least a week after treatment interruption. Results Demographic data were similar between both groups. Clinical cure at 3-4 weeks was more frequently observed with the use of undiluted solution (19/33 vs 3/13 dogs,P= .03) in association with a shorter median duration of treatment (4 vs 6 weeks,P= .01). Dogs from group 2 having less than 1000 cells/mu L in lavage were also more likely to be cured at 3-4 weeks than dogs with more than 1000 cells/mu L [9/9 vs 10/19,P= .006] and median duration of treatment in that subgroup of animals was reduced (3 vs 5 weeks,P= .02). Conclusion and Clinical Importance Aerosolized delivery of gentamicin seems effective for inducing clinical cure inBbinfection. Clinical response appears better using undiluted 5% solution, particularly in the subgroup of dogs having less than 1000 cells/mu L in lavage.