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Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.
Melanie Brügger; Thomas Démoulins; G. Tuba Barut; Beatrice Zumkehr; Blandina I. Oliveira Esteves; Kemal Mehinagic; Quentin Haas; Aline Schögler; Marie-Anne Rameix-Welti; Jean-François Eléouët; Ueli Moehrlen; Thomas M. Marti; Ralph A. Schmid; Artur Summerfield; Horst Posthaus; Nicolas Ruggli; Sean R. R. Hall; Marco P. Alves. Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection. PLOS Pathogens 2021, 17, e1009789 .
AMA StyleMelanie Brügger, Thomas Démoulins, G. Tuba Barut, Beatrice Zumkehr, Blandina I. Oliveira Esteves, Kemal Mehinagic, Quentin Haas, Aline Schögler, Marie-Anne Rameix-Welti, Jean-François Eléouët, Ueli Moehrlen, Thomas M. Marti, Ralph A. Schmid, Artur Summerfield, Horst Posthaus, Nicolas Ruggli, Sean R. R. Hall, Marco P. Alves. Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection. PLOS Pathogens. 2021; 17 (7):e1009789.
Chicago/Turabian StyleMelanie Brügger; Thomas Démoulins; G. Tuba Barut; Beatrice Zumkehr; Blandina I. Oliveira Esteves; Kemal Mehinagic; Quentin Haas; Aline Schögler; Marie-Anne Rameix-Welti; Jean-François Eléouët; Ueli Moehrlen; Thomas M. Marti; Ralph A. Schmid; Artur Summerfield; Horst Posthaus; Nicolas Ruggli; Sean R. R. Hall; Marco P. Alves. 2021. "Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection." PLOS Pathogens 17, no. 7: e1009789.
The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4+ and CD8+ T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.
Thomas Démoulins; Melanie Brügger; Beatrice Zumkehr; Blandina I. Oliveira Esteves; Kemal Mehinagic; Amal Fahmi; Loïc Borcard; Adriano Taddeo; Damian Jandrasits; Horst Posthaus; Charaf Benarafa; Nicolas Ruggli; Marco P. Alves. The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis. PLOS Pathogens 2021, 17, e1009529 .
AMA StyleThomas Démoulins, Melanie Brügger, Beatrice Zumkehr, Blandina I. Oliveira Esteves, Kemal Mehinagic, Amal Fahmi, Loïc Borcard, Adriano Taddeo, Damian Jandrasits, Horst Posthaus, Charaf Benarafa, Nicolas Ruggli, Marco P. Alves. The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis. PLOS Pathogens. 2021; 17 (4):e1009529.
Chicago/Turabian StyleThomas Démoulins; Melanie Brügger; Beatrice Zumkehr; Blandina I. Oliveira Esteves; Kemal Mehinagic; Amal Fahmi; Loïc Borcard; Adriano Taddeo; Damian Jandrasits; Horst Posthaus; Charaf Benarafa; Nicolas Ruggli; Marco P. Alves. 2021. "The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis." PLOS Pathogens 17, no. 4: e1009529.
Contagious 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.
Flavio Sacchini; Anne Mariana Liljander; Martin Heller; Elizabeth Jane Poole; Horst Posthaus; Elise Schieck; Joerg Jores. Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides. Acta Veterinaria Scandinavica 2020, 62, 1 -5.
AMA StyleFlavio Sacchini, Anne Mariana Liljander, Martin Heller, Elizabeth Jane Poole, Horst Posthaus, Elise Schieck, Joerg Jores. Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides. Acta Veterinaria Scandinavica. 2020; 62 (1):1-5.
Chicago/Turabian StyleFlavio Sacchini; Anne Mariana Liljander; Martin Heller; Elizabeth Jane Poole; Horst Posthaus; Elise Schieck; Joerg Jores. 2020. "Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides." Acta Veterinaria Scandinavica 62, no. 1: 1-5.
The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the specific features of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a state-of-the-art model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.
Thomas Demoulins; Melanie Bruegger; Beatrice Zumhehr; Blandina Oliveira Esteves; Kemal Mehinagic; Amal Fahmi; Loic Borcard; Adriano Taddeo; Horst Posthaus; Charaf Benarafa; Nicolas Ruggli; Marco P Alves. The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis. 2020, 1 .
AMA StyleThomas Demoulins, Melanie Bruegger, Beatrice Zumhehr, Blandina Oliveira Esteves, Kemal Mehinagic, Amal Fahmi, Loic Borcard, Adriano Taddeo, Horst Posthaus, Charaf Benarafa, Nicolas Ruggli, Marco P Alves. The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis. . 2020; ():1.
Chicago/Turabian StyleThomas Demoulins; Melanie Bruegger; Beatrice Zumhehr; Blandina Oliveira Esteves; Kemal Mehinagic; Amal Fahmi; Loic Borcard; Adriano Taddeo; Horst Posthaus; Charaf Benarafa; Nicolas Ruggli; Marco P Alves. 2020. "The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis." , no. : 1.
Clostridium perfringens β-toxin (CPB) is a highly active β-pore-forming toxin (β-PFT) and the essential virulence factor for fatal, necro-hemorrhagic enteritis in animals and humans. The molecular mechanisms involved in CPB’s action on its target, the endothelium of small intestinal vessels, are poorly understood. Here, we identify platelet endothelial cell adhesion molecule-1 (CD31 or PECAM-1) as the specific membrane receptor for CPB on endothelial cells. CD31 expression corresponds with the cell-type specificity of CPB, and it is essential for toxicity in cultured cells and mice. Ectopic CD31 expression renders resistant cells and liposomes susceptible to CPB-induced membrane damage. Moreover, the extracellular Ig6 domain of mouse, human, and porcine CD31 is essential for the interaction with CPB. Hence, our results explain the cell-type specificity of CPB in vitro and in the natural disease caused by C. perfringens type C.
Julia Bruggisser; Basma Tarek; Marianne Wyder; Philipp Müller; Christoph von Ballmoos; Guillaume Witz; Gaby Enzmann; Urban Deutsch; Britta Engelhardt; Horst Posthaus. CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell Host & Microbe 2020, 28, 69 -78.e6.
AMA StyleJulia Bruggisser, Basma Tarek, Marianne Wyder, Philipp Müller, Christoph von Ballmoos, Guillaume Witz, Gaby Enzmann, Urban Deutsch, Britta Engelhardt, Horst Posthaus. CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell Host & Microbe. 2020; 28 (1):69-78.e6.
Chicago/Turabian StyleJulia Bruggisser; Basma Tarek; Marianne Wyder; Philipp Müller; Christoph von Ballmoos; Guillaume Witz; Gaby Enzmann; Urban Deutsch; Britta Engelhardt; Horst Posthaus. 2020. "CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin." Cell Host & Microbe 28, no. 1: 69-78.e6.
Clostridium perfringens type C causes severe and lethal necrotic enteritis (NE) in newborn piglets. NE is diagnosed through a combination of pathology and bacteriologic investigations. The hallmark lesion of NE is deep, segmental mucosal necrosis with marked hemorrhage of the small intestine. C. perfringens can be isolated from intestinal samples in acute cases but it is more challenging to identify pathogenic strains in subacute-to-chronic cases. Toxinotyping or genotyping is required to differentiate C. perfringens type C from commensal type A strains. Recent research has extended our knowledge about the pathogenesis of the disease, although important aspects remain to be determined. The pathogenesis involves rapid overgrowth of C. perfringens type C in the small intestine, inhibition of beta-toxin (CPB) degradation by trypsin inhibitors in the colostrum of sows, and most likely initial damage to the small intestinal epithelial barrier. CPB itself acts primarily on vascular endothelial cells in the mucosa and can also inhibit platelet function. Prevention of the disease is achieved by immunization of pregnant sows with C. perfringens type C toxoid vaccines, combined with proper sanitation on farms. For the implementation of prevention strategies, it is important to differentiate between disease-free and pathogen-free status of a herd. The latter is more challenging to maintain, given that C. perfringens type C can persist for a long time in the environment and in the intestinal tract of adult animals and thus can be distributed via clinically and bacteriologically inapparent carrier animals.
Horst Posthaus; Sonja Kittl; Basma Tarek; Julia Bruggisser. Clostridium perfringenstype C necrotic enteritis in pigs: diagnosis, pathogenesis, and prevention. Journal of Veterinary Diagnostic Investigation 2020, 32, 203 -212.
AMA StyleHorst Posthaus, Sonja Kittl, Basma Tarek, Julia Bruggisser. Clostridium perfringenstype C necrotic enteritis in pigs: diagnosis, pathogenesis, and prevention. Journal of Veterinary Diagnostic Investigation. 2020; 32 (2):203-212.
Chicago/Turabian StyleHorst Posthaus; Sonja Kittl; Basma Tarek; Julia Bruggisser. 2020. "Clostridium perfringenstype C necrotic enteritis in pigs: diagnosis, pathogenesis, and prevention." Journal of Veterinary Diagnostic Investigation 32, no. 2: 203-212.
SUMMARYClostridium perfringensβ-toxin (CPB) is a highly active hemolysin β-pore forming toxin and the essential virulence factor for a severe, necro-hemorrhagic enteritis in animals and humans.In vivoandin vitroit exerts a remarkable cell type specificity towards endothelial cells, platelets and some leucocytic cell lines. The target cell specificity of CPB is, however, poorly understood and a receptor explaining this selective toxicity has not been identified. This has hampered further research into the pathogenesis ofC. perfringenstype C induced enteritis. Here we identify Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) as the specific membrane receptor for CPB on endothelial cells. CD31 expression is essential for CPB toxicity in endothelial cells and lethality in mice and sufficient to render previously resistant cells highly susceptible to the toxin. We further demonstrate, that the extracellular membrane proximal Ig6 domain of CD31 is required for the interaction with CPB and that expression of CD31 corresponds with the specificity of the toxin towards cultured cell lines. Our results thus provide an explanation for the cell type specificity of CPB and can be linked to the characteristic lesions observed a devastating enteric disease in animals and humans.
Julia Bruggisser; Basma Tarek; Marianne Wyder; Guillaume Witz; Gaby Enzmann; Urban Deutsch; Britta Engelhardt; Horst Posthaus. Cell-specific targeting byClostridium perfringensβ-toxin unraveled: the role of CD31 as the toxin receptor. 2019, 787242 .
AMA StyleJulia Bruggisser, Basma Tarek, Marianne Wyder, Guillaume Witz, Gaby Enzmann, Urban Deutsch, Britta Engelhardt, Horst Posthaus. Cell-specific targeting byClostridium perfringensβ-toxin unraveled: the role of CD31 as the toxin receptor. . 2019; ():787242.
Chicago/Turabian StyleJulia Bruggisser; Basma Tarek; Marianne Wyder; Guillaume Witz; Gaby Enzmann; Urban Deutsch; Britta Engelhardt; Horst Posthaus. 2019. "Cell-specific targeting byClostridium perfringensβ-toxin unraveled: the role of CD31 as the toxin receptor." , no. : 787242.
Clostridium perfringens type C induced necrotizing enteritis (NE) causes high mortality in newborn piglets. Immunization programs employing commercially available vaccines are used to prevent disease. Sows are vaccinated during every gestation period and piglets take up antibodies from the colostrum. Antibodies against the major clostridial toxin beta-toxin (CPB) are considered essential for protective immunity. Because the pathogen can persist for several years on farms, continuous vaccination is essential to protect pig herds from the re-occurrence of NE. In two field trials using commercially available vaccines we monitored neutralizing anti-CPB antibodies in pigs after vaccination. The first trial compared antibody titers in primiparous (gilts) and multiparous sows and their piglets after vaccination. A proportion of gilts and their piglets’ showed no or low antibody titers. All multiparous sows developed significantly higher serum and colostrum antibody titers after a booster vaccination shortly before their next farrowing. These colostral antibody titer highly correlated with the serum antibody titer of their piglets after consumption of colostrum. In a second field trial, we adapted the vaccination schemes using 3 instead of 2 initial vaccinations before the first farrowing of gilts. This significantly increased serum and colostrum antibody titers in gilts and serum antibody titers in piglets. We demonstrate that despite following recommended vaccination protocols, a proportion of gilts might not sufficiently seroconvert to provide efficient passive immunity to their offsprings. A simple adaptation of the vaccination scheme can however improve passive protection of piglets from NE.
Olivia K. Richard; Alexander Grahofer; Heiko Nathues; Horst Posthaus. Vaccination against Clostridium perfringens type C enteritis in pigs: a field study using an adapted vaccination scheme. Porcine Health Management 2019, 5, 1 -9.
AMA StyleOlivia K. Richard, Alexander Grahofer, Heiko Nathues, Horst Posthaus. Vaccination against Clostridium perfringens type C enteritis in pigs: a field study using an adapted vaccination scheme. Porcine Health Management. 2019; 5 (1):1-9.
Chicago/Turabian StyleOlivia K. Richard; Alexander Grahofer; Heiko Nathues; Horst Posthaus. 2019. "Vaccination against Clostridium perfringens type C enteritis in pigs: a field study using an adapted vaccination scheme." Porcine Health Management 5, no. 1: 1-9.
Animal diseases due to mycoplasmas are a major cause of morbidity and mortality associated with economic losses for farmers all over the world. Currently used mycoplasma vaccines exhibit several drawbacks, including low efficacy, short time of protection, adverse reactions, and difficulty in differentiating infected from vaccinated animals. Therefore, there is a need for improved vaccines to control animal mycoplasmoses. Here, we used genome engineering tools derived from synthetic biology approaches to produce targeted mutations in the essential GTPase-encoding obg gene of Mycoplasma mycoides subsp. capri . Some of the resulting mutants exhibited a marked temperature-sensitive phenotype. The virulence of one of the obg mutants was evaluated in a caprine septicemia model and found to be strongly reduced. Although the obg mutant reverted to a virulent phenotype in one infected animal, we believe that these results contribute to a strategy that should help in building new vaccines against animal mycoplasmoses.
Carole Lartigue; Yanina Valverde Timana; Fabien Labroussaa; Elise Schieck; Anne Liljander; Flavio Sacchini; Horst Posthaus; Brigitte Batailler; Pascal Sirand-Pugnet; Sanjay Vashee; Joerg Jores; Alain Blanchard. Attenuation of a Pathogenic Mycoplasma Strain by Modification of the obg Gene by Using Synthetic Biology Approaches. mSphere 2019, 4, e00030-19 .
AMA StyleCarole Lartigue, Yanina Valverde Timana, Fabien Labroussaa, Elise Schieck, Anne Liljander, Flavio Sacchini, Horst Posthaus, Brigitte Batailler, Pascal Sirand-Pugnet, Sanjay Vashee, Joerg Jores, Alain Blanchard. Attenuation of a Pathogenic Mycoplasma Strain by Modification of the obg Gene by Using Synthetic Biology Approaches. mSphere. 2019; 4 (3):e00030-19.
Chicago/Turabian StyleCarole Lartigue; Yanina Valverde Timana; Fabien Labroussaa; Elise Schieck; Anne Liljander; Flavio Sacchini; Horst Posthaus; Brigitte Batailler; Pascal Sirand-Pugnet; Sanjay Vashee; Joerg Jores; Alain Blanchard. 2019. "Attenuation of a Pathogenic Mycoplasma Strain by Modification of the obg Gene by Using Synthetic Biology Approaches." mSphere 4, no. 3: e00030-19.
Background: Beta-toxin (CPB) is the major virulence factor of Clostridium perfringens type C, causing hemorrhagic enteritis in newborn pigs but also other animals and humans. Vaccines containing inactivated CPB are known to induce protective antibody titers in sow colostrum and neutralization of the CPB activity is thought to be essential for protective immunity in newborn piglets. However, no method is available to quantify the neutralizing effect of vaccine-induced antibody titers in pigs. (2) Methods: We developed a novel assay for the quantification of neutralizing anti-CPB antibodies. Sera and colostrum of sows immunized with a commercial C. perfringens type A and C vaccine was used to determine neutralizing effects on CPB induced cytotoxicity in endothelial cells. Antibody titers of sows and their piglets were determined and compared to results obtained by an ELISA. (3) Results: Vaccinated sows developed neutralizing antibodies against CPB in serum and colostrum. Multiparous sows developed higher serum and colostrum antibody titers after booster vaccinations than uniparous sows. The antibody titers of sows and those of their piglets correlated highly. Piglets from vaccinated sows were protected against intraperitoneal challenge with C. perfringens type C supernatant. (4) Conclusions: The test based on primary porcine endothelial cells quantifies neutralizing antibody activity in serum and colostrum of vaccinated sows and could be used to reduce and refine animal experimentation during vaccine development.
Olivia K. Richard; Sven Springer; Jacqueline Finzel; Tobias Theuß; Marianne Wyder; Beatriz Vidondo; Horst Posthaus. Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial. Toxins 2019, 11, 225 .
AMA StyleOlivia K. Richard, Sven Springer, Jacqueline Finzel, Tobias Theuß, Marianne Wyder, Beatriz Vidondo, Horst Posthaus. Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial. Toxins. 2019; 11 (4):225.
Chicago/Turabian StyleOlivia K. Richard; Sven Springer; Jacqueline Finzel; Tobias Theuß; Marianne Wyder; Beatriz Vidondo; Horst Posthaus. 2019. "Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial." Toxins 11, no. 4: 225.
Mycoplasmas are the smallest free-living organisms and cause a number of economically important diseases affecting humans, animals, insects, and plants. Here, we demonstrate that highly virulent Mycoplasma mycoides subspecies capri (Mmc) can be fully attenuated via targeted deletion of non-essential genes encoding, among others, potential virulence traits. Five genomic regions, representing approximately 10% of the original Mmc genome, were successively deleted using Saccharomyces cerevisiae as an engineering platform. Specifically, a total of 68 genes out of the 432 genes verified to be individually non-essential in the JCVI-Syn3.0 minimal cell, were excised from the genome. In vitro characterization showed that this mutant was similar to its parental strain in terms of its doubling time, even though 10% of the genome content were removed. A novel in vivo challenge model in goats revealed that the wild-type parental strain caused marked necrotizing inflammation at the site of inoculation, septicemia and all animals reached endpoint criteria within 6 days after experimental infection. This is in contrast to the mutant strain, which caused no clinical signs nor pathomorphological lesions. These results highlight, for the first time, the rational design, construction and complete attenuation of a Mycoplasma strain via synthetic genomics tools. Trait addition using the yeast-based genome engineering platform and subsequent in vitro or in vivo trials employing the Mycoplasma chassis will allow us to dissect the role of individual candidate Mycoplasma virulence factors and lead the way for the development of an attenuated designer vaccine.
Joerg Jores; Li Ma; Paul Ssajjakambwe; Elise Schieck; Anne Liljander; Suchismita Chandran; Michael H. Stoffel; Valentina Cippa; Yonathan Arfi; Nacyra Assad-Garcia; Laurent Falquet; Pascal Sirand-Pugnet; Alain Blanchard; Carole Lartigue; Horst Posthaus; Fabien Labroussaa; Sanjay Vashee. Removal of a Subset of Non-essential Genes Fully Attenuates a Highly Virulent Mycoplasma Strain. Frontiers in Microbiology 2019, 10, 664 .
AMA StyleJoerg Jores, Li Ma, Paul Ssajjakambwe, Elise Schieck, Anne Liljander, Suchismita Chandran, Michael H. Stoffel, Valentina Cippa, Yonathan Arfi, Nacyra Assad-Garcia, Laurent Falquet, Pascal Sirand-Pugnet, Alain Blanchard, Carole Lartigue, Horst Posthaus, Fabien Labroussaa, Sanjay Vashee. Removal of a Subset of Non-essential Genes Fully Attenuates a Highly Virulent Mycoplasma Strain. Frontiers in Microbiology. 2019; 10 ():664.
Chicago/Turabian StyleJoerg Jores; Li Ma; Paul Ssajjakambwe; Elise Schieck; Anne Liljander; Suchismita Chandran; Michael H. Stoffel; Valentina Cippa; Yonathan Arfi; Nacyra Assad-Garcia; Laurent Falquet; Pascal Sirand-Pugnet; Alain Blanchard; Carole Lartigue; Horst Posthaus; Fabien Labroussaa; Sanjay Vashee. 2019. "Removal of a Subset of Non-essential Genes Fully Attenuates a Highly Virulent Mycoplasma Strain." Frontiers in Microbiology 10, no. : 664.
Echinococcus multilocularis is the etiologic agent of alveolar echinococcosis (AE), a severe and potentially fatal larval cestode infection primarily affecting the liver. AE is known to occur in dead-end intermediate hosts, including humans and nonhuman primates. Between 1999 and 2016, AE was diagnosed in seven western lowland gorillas (Gorilla gorilla gorilla), all from a Swiss zoo. Six gorillas died of the disease. One individual is still alive, receives continuous albendazole medication, and shows no clinical signs. Most infected animals remained asymptomatic for years. Only one young gorilla showed early signs of acute discomfort and abdominal pain. In the final stage of the disease, affected animals died suddenly, or showed a short course of nonspecific but severe clinical signs, including lethargy, recumbency, abdominal enlargement, and anorexia. Postmortem examination confirmed hepatic AE complicated by peritonitis in most cases. Echinococcus multilocularis infection may remain undetected because of a very long incubation period. Hematological and biochemical parameters rarely showed abnormalities in this phase. Thus, inclusion of abdominal hepatic ultrasound examination and serology is recommended for early AE detection in routine examinations of gorillas in endemic areas or where food is potentially contaminated with E. multilocularis eggs. Ultrasound or computed tomography was useful to monitor progression and to estimate the volumetric extension of the hepatic lesions. Current medication with albendazole, which proved to be effective for human patients, was not able to stop progression of hepatic lesions in gorillas. Therefore, its therapeutic value remains questionable in gorillas. However, long-term oral albendazole treatment proved to be safe, and therapeutic plasma levels published for humans were achieved. Preventive measures such as thermo-treatment of food or vaccination of gorillas and other nonhuman primates should be considered in areas where E. multilocularis is present.
Christian Wenker; Stefan Hoby; Fabia Wyss; Bernard Mengiardi; Renate Vögtli; Horst Posthaus; Peter Deplazes; Bruno Gottstein. ALVEOLAR ECHINOCOCCOSIS IN WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA): ALBENDAZOLE WAS NOT ABLE TO STOP PROGRESSION OF THE DISEASE. Journal of Zoo and Wildlife Medicine 2019, 50, 243 -253.
AMA StyleChristian Wenker, Stefan Hoby, Fabia Wyss, Bernard Mengiardi, Renate Vögtli, Horst Posthaus, Peter Deplazes, Bruno Gottstein. ALVEOLAR ECHINOCOCCOSIS IN WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA): ALBENDAZOLE WAS NOT ABLE TO STOP PROGRESSION OF THE DISEASE. Journal of Zoo and Wildlife Medicine. 2019; 50 (1):243-253.
Chicago/Turabian StyleChristian Wenker; Stefan Hoby; Fabia Wyss; Bernard Mengiardi; Renate Vögtli; Horst Posthaus; Peter Deplazes; Bruno Gottstein. 2019. "ALVEOLAR ECHINOCOCCOSIS IN WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA): ALBENDAZOLE WAS NOT ABLE TO STOP PROGRESSION OF THE DISEASE." Journal of Zoo and Wildlife Medicine 50, no. 1: 243-253.
Mycoplasmas are the smallest free-living organisms and cause a number of economically important diseases affecting humans, animals, insects and plants. Here, we demonstrate that highly virulentMycoplasma mycoidessubspeciescapri(Mmc) can be fully attenuatedviatargeted deletion of non-essential genes encoding, among others, potential virulence traits. Five genomic regions, representing approximately ten percent of the originalMmcgenome, were successively deleted usingSaccharomyces cerevisiaeas an engineering platform. Specifically, a total of 68 genes out of the 432 genes verified to be individually nonessential in the JCVI-Syn3.0 minimal cell, were excised from the genome.In vitrocharacterization showed that this mutant was similar to its parental strain in terms of its doubling time, even though ten percent of the genome content were removed. A novelin vivochallenge model in goats revealed that the wild-type parental strain caused marked necrotizing inflammation at the site of inoculation, septicemia and all animals reaching endpoint criteria within seven days after experimental infection. This is in contrast to the mutant strain, which caused no clinical signs nor pathomorphological lesions. These results highlight, for the first time, the rational design, construction and complete attenuation of aMycoplasmastrain via synthetic genomics tools. Trait addition using the yeast-based genome engineering platform and subsequentin vitroorin vivotrials employing theMycoplasmachassis will allow us to dissect the role of individual candidateMycoplasmavirulence factors and lead the way for the development of an attenuated designer vaccine.IMPORTANCEMembers of theMycoplasma mycoidescluster cause important animal plaques in Africa and Asia, which impact animal welfare, provision of food and the life of thousands of small-scale farmers. We applied synthetic biology tools toMycoplasma mycoidesin order to design and create a fully attenuatedMycoplasmastrain that was subsequently confirmedin vivousing a novel caprine infection model. This is the first time that aMycoplasmamutant developed by applying synthetic biology tools has been testedin vivoto pin point candidate virulence traits. The mutant strain is similar to “apathogenicE. coliK12” strains that boosted the research on host-pathogen interactions for the genusEscherichiaand other bacterial genera.
Joerg Jores; Li Ma; Paul Ssajjakambwe; Elise Schieck; Anne M Liljander; Suchismita Chandran; Michael H Stoffel; Valentina L Cippa; Yonathan Arfi; Nacyra Asad-Garcia; Laurent Falquet; Pascal Sirand-Pugnet; Alain Blanchard; Carole Lartigue; Horst Posthaus; Fabien Labroussaa; Sanjay Vashee. Removal of a subset of non-essential genes fully attenuates a highly virulentMycoplasmastrain. 2019, 508978 .
AMA StyleJoerg Jores, Li Ma, Paul Ssajjakambwe, Elise Schieck, Anne M Liljander, Suchismita Chandran, Michael H Stoffel, Valentina L Cippa, Yonathan Arfi, Nacyra Asad-Garcia, Laurent Falquet, Pascal Sirand-Pugnet, Alain Blanchard, Carole Lartigue, Horst Posthaus, Fabien Labroussaa, Sanjay Vashee. Removal of a subset of non-essential genes fully attenuates a highly virulentMycoplasmastrain. . 2019; ():508978.
Chicago/Turabian StyleJoerg Jores; Li Ma; Paul Ssajjakambwe; Elise Schieck; Anne M Liljander; Suchismita Chandran; Michael H Stoffel; Valentina L Cippa; Yonathan Arfi; Nacyra Asad-Garcia; Laurent Falquet; Pascal Sirand-Pugnet; Alain Blanchard; Carole Lartigue; Horst Posthaus; Fabien Labroussaa; Sanjay Vashee. 2019. "Removal of a subset of non-essential genes fully attenuates a highly virulentMycoplasmastrain." , no. : 508978.
Capsular polysaccharides have been confirmed to be an important virulence trait in many gram-positive and gram-negative bacteria. Similarly, they are proposed to be virulence traits in minimal Mycoplasma that cause disease in humans and animals. In the current study, goats were infected with the caprine pathogen Mycoplasma mycoides subsp. capri or an engineered mutant lacking the capsular polysaccharide, galactofuranose. Goats infected with the mutant strain showed only transient fever. In contrast, 5 of 8 goats infected with the parental strain reached end-point criteria after infection. These findings confirm that galactofuranose is a virulence factor in M. mycoides.
Joerg Jores; Elise Schieck; Anne Liljander; Flavio Sacchini; Horst Posthaus; Carole Lartigue; Alain Blanchard; Fabien Labroussaa; Sanjay Vashee. In vivo role of capsular polysaccharide in Mycoplasma mycoides. Journal of Infectious Diseases 2018, 219, 1559 -1563.
AMA StyleJoerg Jores, Elise Schieck, Anne Liljander, Flavio Sacchini, Horst Posthaus, Carole Lartigue, Alain Blanchard, Fabien Labroussaa, Sanjay Vashee. In vivo role of capsular polysaccharide in Mycoplasma mycoides. Journal of Infectious Diseases. 2018; 219 (10):1559-1563.
Chicago/Turabian StyleJoerg Jores; Elise Schieck; Anne Liljander; Flavio Sacchini; Horst Posthaus; Carole Lartigue; Alain Blanchard; Fabien Labroussaa; Sanjay Vashee. 2018. "In vivo role of capsular polysaccharide in Mycoplasma mycoides." Journal of Infectious Diseases 219, no. 10: 1559-1563.
Observational studies are a basis for much of our knowledge of veterinary pathology, yet considerations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offered advice on planning and carrying out an observational study. Part 2 of the series focuses on methodology. Our general recommendations are to consider using already-validated methods, published guidelines, data from primary sources, and quantitative analyses. We discuss 3 common methods in pathology research—histopathologic scoring, immunohistochemistry, and polymerase chain reaction—to illustrate principles of method validation. Some aspects of quality control include use of clear objective grading criteria, validation of key reagents, assessing sample quality, determining specificity and sensitivity, use of technical and biologic negative and positive controls, blinding of investigators, approaches to minimizing operator-dependent variation, measuring technical variation, and consistency in analysis of the different study groups. We close by discussing approaches to increasing the rigor of observational studies by corroborating results with complementary methods, using sufficiently large numbers of study subjects, consideration of the data in light of similar published studies, replicating the results in a second study population, and critical analysis of the study findings.
Jeff L. Caswell; Laura L. Bassel; Jamie L. Rothenburger; Andrea Gröne; Jan M. Sargeant; Amanda P. Beck; Stina Ekman; Katherine Gibson-Corley; Thijs Kuiken; Elise E. B. LaDouceur; David K. Meyerholz; Francesco C. Origgi; Horst Posthaus; Simon L. Priestnall; Lorenzo Ressel; Leslie Sharkey; Leandro B. C. Teixeira; Kazuyuki Uchida; Jerrold M. Ward; Joshua D. Webster; Jyoji Yamate. Observational Study Design in Veterinary Pathology, Part 2: Methodology. Veterinary Pathology 2018, 55, 774 -785.
AMA StyleJeff L. Caswell, Laura L. Bassel, Jamie L. Rothenburger, Andrea Gröne, Jan M. Sargeant, Amanda P. Beck, Stina Ekman, Katherine Gibson-Corley, Thijs Kuiken, Elise E. B. LaDouceur, David K. Meyerholz, Francesco C. Origgi, Horst Posthaus, Simon L. Priestnall, Lorenzo Ressel, Leslie Sharkey, Leandro B. C. Teixeira, Kazuyuki Uchida, Jerrold M. Ward, Joshua D. Webster, Jyoji Yamate. Observational Study Design in Veterinary Pathology, Part 2: Methodology. Veterinary Pathology. 2018; 55 (6):774-785.
Chicago/Turabian StyleJeff L. Caswell; Laura L. Bassel; Jamie L. Rothenburger; Andrea Gröne; Jan M. Sargeant; Amanda P. Beck; Stina Ekman; Katherine Gibson-Corley; Thijs Kuiken; Elise E. B. LaDouceur; David K. Meyerholz; Francesco C. Origgi; Horst Posthaus; Simon L. Priestnall; Lorenzo Ressel; Leslie Sharkey; Leandro B. C. Teixeira; Kazuyuki Uchida; Jerrold M. Ward; Joshua D. Webster; Jyoji Yamate. 2018. "Observational Study Design in Veterinary Pathology, Part 2: Methodology." Veterinary Pathology 55, no. 6: 774-785.
Martina Dettwiler; Kemal Mehinagic; S Gobeli Brawand; A Thomann; S Feyer; L Hüsser; G Theubet; J Gigandet; S Rottenberg; Horst Posthaus. Bacillus anthracis as a cause of bovine abortion – a necropsy case requiring special biosafety measures. Schweiz Arch Tierheilkd 2018, 160, 547 -552.
AMA StyleMartina Dettwiler, Kemal Mehinagic, S Gobeli Brawand, A Thomann, S Feyer, L Hüsser, G Theubet, J Gigandet, S Rottenberg, Horst Posthaus. Bacillus anthracis as a cause of bovine abortion – a necropsy case requiring special biosafety measures. Schweiz Arch Tierheilkd. 2018; 160 (9):547-552.
Chicago/Turabian StyleMartina Dettwiler; Kemal Mehinagic; S Gobeli Brawand; A Thomann; S Feyer; L Hüsser; G Theubet; J Gigandet; S Rottenberg; Horst Posthaus. 2018. "Bacillus anthracis as a cause of bovine abortion – a necropsy case requiring special biosafety measures." Schweiz Arch Tierheilkd 160, no. 9: 547-552.
Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods.
Jeff L. Caswell; Laura L. Bassel; Jamie L. Rothenburger; Andrea Gröne; Jan M. Sargeant; Amanda P. Beck; Stina Ekman; Katherine Gibson-Corley; Thijs Kuiken; Elise E. B. LaDouceur; David K. Meyerholz; Francesco C. Origgi; Horst Posthaus; Simon L. Priestnall; Lorenzo Ressel; Leslie Sharkey; Leandro B. C. Teixeira; Kazuyuki Uchida; Jerrold M. Ward; Joshua D. Webster; Jyoji Yamate. Observational Study Design in Veterinary Pathology, Part 1: Study Design. Veterinary Pathology 2018, 55, 607 -621.
AMA StyleJeff L. Caswell, Laura L. Bassel, Jamie L. Rothenburger, Andrea Gröne, Jan M. Sargeant, Amanda P. Beck, Stina Ekman, Katherine Gibson-Corley, Thijs Kuiken, Elise E. B. LaDouceur, David K. Meyerholz, Francesco C. Origgi, Horst Posthaus, Simon L. Priestnall, Lorenzo Ressel, Leslie Sharkey, Leandro B. C. Teixeira, Kazuyuki Uchida, Jerrold M. Ward, Joshua D. Webster, Jyoji Yamate. Observational Study Design in Veterinary Pathology, Part 1: Study Design. Veterinary Pathology. 2018; 55 (5):607-621.
Chicago/Turabian StyleJeff L. Caswell; Laura L. Bassel; Jamie L. Rothenburger; Andrea Gröne; Jan M. Sargeant; Amanda P. Beck; Stina Ekman; Katherine Gibson-Corley; Thijs Kuiken; Elise E. B. LaDouceur; David K. Meyerholz; Francesco C. Origgi; Horst Posthaus; Simon L. Priestnall; Lorenzo Ressel; Leslie Sharkey; Leandro B. C. Teixeira; Kazuyuki Uchida; Jerrold M. Ward; Joshua D. Webster; Jyoji Yamate. 2018. "Observational Study Design in Veterinary Pathology, Part 1: Study Design." Veterinary Pathology 55, no. 5: 607-621.
Hepatozoon silvestris is an emerging apicomplexan parasite discovered in European wild cats from Bosnia and Herzegovina and blood samples of a domestic cat from Southern Italy in 2017. It has also been identified in Ixodes ricinus collected from a domestic cat in Wales, UK, in 2018. The clinical relevance, pathogenesis and epidemiology of this novel Hepatozoon species are not yet understood. Thus, the objective of this paper was to report and describe the first fatal case of an H. silvestris infection in a domestic cat. The cat, which originated from Switzerland, died shortly after presenting clinical signs of lethargy, weakness and anorexia. At necropsy, no specific lesions were observed. Histopathology of the heart revealed a severe lympho-plasmacytic and histiocytic myocarditis. Mature and developing protozoal meronts morphologically compatible with Hepatozoon species were observed associated with the myocardial inflammation. No other lesions were present in any other organ evaluated, and the cat tested negative for retroviral and other immunosuppressive infectious agents. Polymerase chain reaction from the myocardium resulted in a specific amplicon of the Hepatozoon 18S rRNA gene. Sequencing and BLAST analysis revealed 100% sequence identity with H. silvestris. The severity of the infection with fatal outcome in an otherwise healthy animal suggests a high virulence of H. silvestris for domestic cats. The presence of this emerging parasite in a domestic cat in Switzerland with no travel history provides further evidence for a geographical distribution throughout Europe.
Kristel Kegler; Ursina Nufer; Amer Alic; Horst Posthaus; Philipp Olias; Walter Basso. Fatal infection with emerging apicomplexan parasite Hepatozoon silvestris in a domestic cat. Parasites & Vectors 2018, 11, 428 .
AMA StyleKristel Kegler, Ursina Nufer, Amer Alic, Horst Posthaus, Philipp Olias, Walter Basso. Fatal infection with emerging apicomplexan parasite Hepatozoon silvestris in a domestic cat. Parasites & Vectors. 2018; 11 (1):428.
Chicago/Turabian StyleKristel Kegler; Ursina Nufer; Amer Alic; Horst Posthaus; Philipp Olias; Walter Basso. 2018. "Fatal infection with emerging apicomplexan parasite Hepatozoon silvestris in a domestic cat." Parasites & Vectors 11, no. 1: 428.
Animal health data recorded in free text, such as in necropsy reports, can have valuable information for national surveillance systems. However, these data are rarely utilized because the text format requires labor-intensive classification of records before they can be analyzed with using statistical or other software. In a previous study, we designed a text-mining tool to extract data from text in necropsy reports. In the current study, we used the tool to extract data from the reports from pig and cattle necropsies performed between 2000 and 2011 at the Institute of Animal Pathology (ITPA), University of Bern, Switzerland. We evaluated data quality in terms of credibility, completeness and representativeness of the Swiss pig and cattle populations. Data was easily extracted from necropsy reports. Data quality in terms of completeness and validity varied a lot depending on the type of data reported. Diseases of the gastrointestinal system were reported most frequently (54.6% of pig submissions and 40.8% of cattle submissions). Diseases affecting serous membranes were reported in 16.0% of necropsied pigs and 27.6% of cattle. Respiratory diseases were reported in 18.3% of pigs and 21.6% of cattle submissions. This study suggests that extracting data from necropsy reports can provide information of value for animal health surveillance. This data has potential value for monitoring endemic disease syndromes in different age and production groups, or for early detection of emerging or re-emerging diseases. The study identified data entry and other errors that could be corrected to improve the quality and validity of the data. Submissions to veterinary diagnostic laboratories have selection biases and these should be considered when designing surveillance systems that include necropsy reports.
Susanne Küker; Celine Faverjon; Lenz Furrer; John Berezowski; Horst Posthaus; Fabio Rinaldi; Flavie Vial. The value of necropsy reports for animal health surveillance. BMC Veterinary Research 2018, 14, 191 .
AMA StyleSusanne Küker, Celine Faverjon, Lenz Furrer, John Berezowski, Horst Posthaus, Fabio Rinaldi, Flavie Vial. The value of necropsy reports for animal health surveillance. BMC Veterinary Research. 2018; 14 (1):191.
Chicago/Turabian StyleSusanne Küker; Celine Faverjon; Lenz Furrer; John Berezowski; Horst Posthaus; Fabio Rinaldi; Flavie Vial. 2018. "The value of necropsy reports for animal health surveillance." BMC Veterinary Research 14, no. 1: 191.
M Schediwy; S Balmer; C Bredtmann; D Hadorn; P Bless; G Rosato; T Sydler; M Harisberger; R Graage; H Saura-Martinez; H Posthaus; C Gurtner. Reviving post-mortem diagnostics as a tool to increase porcine herd health and strengthen early detection of pig diseases – the PathoPig project 2014-2016. Schweiz Arch Tierheilkd 2018, 160, 375 -384.
AMA StyleM Schediwy, S Balmer, C Bredtmann, D Hadorn, P Bless, G Rosato, T Sydler, M Harisberger, R Graage, H Saura-Martinez, H Posthaus, C Gurtner. Reviving post-mortem diagnostics as a tool to increase porcine herd health and strengthen early detection of pig diseases – the PathoPig project 2014-2016. Schweiz Arch Tierheilkd. 2018; 160 (6):375-384.
Chicago/Turabian StyleM Schediwy; S Balmer; C Bredtmann; D Hadorn; P Bless; G Rosato; T Sydler; M Harisberger; R Graage; H Saura-Martinez; H Posthaus; C Gurtner. 2018. "Reviving post-mortem diagnostics as a tool to increase porcine herd health and strengthen early detection of pig diseases – the PathoPig project 2014-2016." Schweiz Arch Tierheilkd 160, no. 6: 375-384.