Article
Veterinary Sciences
Kamonpun Chuekwon, Chun-Yen Chu, Li-Ting Cheng
Summary: The study shows that the N-terminus of flagellin (nFliC) is a versatile and potent adjuvant for vaccine formulation. Both genetic fusion and simple admixture of nFliC with the antigen ApxIIPF enhance humoral and cellular immune responses, and increase vaccine protective efficacy. Even without supplemental adjuvants, genetically linked nFliC still provides significant immune enhancement.
BMC VETERINARY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jone Amuategi, Rocio Alonso, Helena Ostolaza
Summary: Adenylate Cyclase Toxin (ACT) is an important virulence factor secreted by Bordetella pertussis, and its activities depend on its interaction with membrane cholesterol and the stabilization of transmembrane helices. Our study provides insights into the molecular mechanisms underlying the dependence of ACT activities on cholesterol and the modulation of toxicity in pore-forming toxins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jana Holubova, Attila Juhasz, Jiri Masin, Ondrej Stanek, David Jurnecka, Adriana Osickova, Peter Sebo, Radim Osicka
Summary: The whooping cough agent, Bordetella pertussis, secretes a toxin-hemolysin that affects host cells by increasing cAMP levels and forming pores, however, enhancing or reducing the pore-forming activity does not significantly alter its virulence in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Andrea M. DiVenere, Dzifa Amengor, Rui P. Silva, Jory A. Goldsmith, Jason S. McLellan, Jennifer A. Maynard
Summary: This study demonstrates the protective role of neutralizing antibodies against ACT in pertussis infection. These antibodies can synergistically interact with antibodies against current vaccine antigens, providing protection against pertussis infection.
Article
Chemistry, Multidisciplinary
Alexis Voegele, Mirko Sadi, Darragh Patrick O'Brien, Pauline Gehan, Dorothee Raoux-Barbot, Maryline Davi, Sylviane Hoos, Sebastien Brule, Bertrand Raynal, Patrick Weber, Ariel Mechaly, Ahmed Haouz, Nicolas Rodriguez, Patrice Vachette, Dominique Durand, Sebastien Brier, Daniel Ladant, Alexandre Chenal
Summary: The P454 segment of the CyaA toxin is capable of translocating across membranes and interacting with calmodulin, with key residues involved in membrane destabilization and calmodulin binding. Inhibitors of calmodulin can efficiently block CyaA internalization. This suggests a potential mechanism for the vectorial translocation of the toxin into host cells.
Article
Multidisciplinary Sciences
Siou-Cen Li, Yu-Tsen Cheng, Ching-Yang Wang, Jia-Ying Wu, Zeng-Weng Chen, Jyh-Perng Wang, Jiunn-Horng Lin, Shih-Ling Hsuan
Summary: This study reveals that ApxI exotoxin induces cytotoxicity in porcine alveolar macrophages by downregulating the activity of FAK and Akt. Preincubation with a CD18 antibody reduces ApxI-induced cytotoxicity, and ectopic expression of pLFA-1 renders cells more susceptible to ApxI. Furthermore, the attenuation of FAK activity by ApxI contributes to subsequent cell death, as demonstrated in FAK-deficient MEFs.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Stelli G. Stancheva, Janna Frombling, Elena L. Sassu, Isabel Hennig-Pauka, Andrea Ladinig, Wilhelm Gerner, Tom Grunert, Monika Ehling-Schulz
Summary: This study provides an in-depth analysis of the exoproteome of Actinobacillus pleuropneumoniae serotype 2, revealing potential therapeutic and vaccine targets and highlighting differences in the immune response to different Apx toxins.
MICROBIAL PATHOGENESIS
(2022)
Article
Multidisciplinary Sciences
Anna Lepesheva, Adriana Osickova, Jana Holubova, David Jurnecka, Sarka Knoblochova, Carlos Espinosa-Vinals, Ladislav Bumba, Karolina Skopova, Radovan Fiser, Radim Osicka, Peter Sebo, Jiri Masin
Summary: The study focused on the impact of pore-forming repeats in toxins on target cell membrane, with findings indicating that the aromatic side chain of the Y940 residue plays a crucial role in the functional folding of CyaA. Substitution of Y940 in the acylated segment of CyaA can lead to self-aggregation and impairment of toxin function.
SCIENTIFIC REPORTS
(2021)
Article
Veterinary Sciences
Kamonpun Chuekwon, Chun-Yen Chu, Li-Ting Cheng
Summary: The hemolytic/leukolytic toxins ApxI, II and III are important in the pathogenicity of Actinobacillus pleuropneumoniae and can serve as effective vaccine antigens. This study aimed to determine if only the pore-forming domain of the toxins is sufficient for protective immunity. Mice were vaccinated with these domains and showed significant antibody and cellular immune responses. In a challenge test, the pore-forming domains of ApxI, II, III and three of them provided varying levels of protection. The pore-forming domain of Apx toxins holds promise as a vaccine antigen against A. pleuropneumoniae.
THAI JOURNAL OF VETERINARY MEDICINE
(2023)
Article
Veterinary Sciences
Eduardo Hernandez-Cuellar, Alma Lilian Guerrero-Barrera, Francisco Javier Avelar-Gonzalez, Juan Manuel Diaz, Jesus Chavez-Reyes, Alfredo Salazar de Santiago
Summary: This study demonstrated the induction of rapid cell death by ApxI in porcine respiratory epithelial cells and endothelial cells, which is dependent on the activation of caspase-1 via the NLRP3 inflammasome. Inhibition of the NLRP3 inflammasome or blocking K+ efflux can reduce ApxI-induced cell death.
VETERINARY RECORD OPEN
(2021)
Article
Cell Biology
Illiassou H. Soumana, Kalyan K. Dewan, Bodo Linz, Israel Rivera, Longhuan Ma, Laura K. Howard, Amanda D. Caulfield, Colleen J. Sedney, Uriel Blas-Machado, Peter Sebo, Eric T. Harvill
Summary: Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis. Researchers have developed a new experimental model that simulates the viral stage of the disease, aiding in the study of bacterial factors that contribute to its transmission.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biophysics
Claudio Piselli, Lorraine Benier, Cornelia Koy, Michael O. Glocker, Roland Benz
Summary: The cell wall of Rhodococcus corynebacteroides and Rhodococcus ruber contains cell wall channels formed by polypeptide subunits, which may belong to a large protein family (PF09203) that forms MspA-like cell wall channels. These proteins are able to form channels in lipid bilayers.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2022)
Article
Microbiology
Jana Holubova, Ondrej Stanek, Attila Juhasz, Illiassou Hamidou Soumana, Peter Makovicky, Peter Sebo
Summary: Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality. This study successfully established a new mouse model to study the transmission and host mechanisms of B. pertussis, providing new insights for future vaccine development.
Article
Microbiology
Nela Klimova, Jana Holubova, Gaia Streparola, Jakub Tomala, Ludmila Brazdilova, Ondrej Stanek, Ladislav Bumba, Peter Sebo
Summary: The pertussis toxin PT inhibits migration of infected dendritic cells from the lungs to the draining lymph nodes, delaying the induction of adaptive serum antibody responses to infection. This suggests that PT action allows time for B. pertussis proliferation on the airway mucosa to facilitate transmission among humans.
Article
Multidisciplinary Sciences
Jan Felix, Ladislav Bumba, Clarissa Liesche, Angelique Fraudeau, Fabrice Rebeille, Jessica Y. El Khoury, Karine Huard, Benoit Gallet, Christine Moriscot, Jean-Philippe Kleman, Yoan Duhoo, Matthew Jessop, Eaazhisai Kandiah, Frederic Barras, Juliette Jouhet, Irina Gutsche
Summary: The membrane lipid composition is a key factor for bacterial stress adaptation. The ravA-viaA pathway responds to aminoglycosides under anaerobic conditions and is involved in cell membrane regulation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Claudio Piselli, Vinaya Kumar Golla, Roland Benz, Ulrich Kleinekathoefer
Summary: This study focuses on the characterization of the lysine cluster in OprO, a porin protein in the outer membrane of Pseudomonas aeruginosa. The importance of lysine residues in ion conductance and phosphate ion flow was demonstrated through experiments and simulations. The results suggest that an improved understanding of lysine residues and ion mobility could lead to the development of more effective antibiotics for P. aeruginosa.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Article
Biochemistry & Molecular Biology
Michaela Hovorkova, Jakub Cerveny, Ladislav Bumba, Helena Pelantova, Josef Cvacka, Vladimir Kren, Olivier Renaudet, David Goyard, Pavla Bojarova
Summary: A new type of glycoconjugate with low nanomolar affinity was developed to inhibit galectins of interest for biomedical research. The presentation of carbohydrate ligands on specific structural scaffolds was found to impact the affinity and selectivity to different galectins.
BIOORGANIC CHEMISTRY
(2023)
Article
Microbiology
Klara Latrova, Tereza Dolejsova, Lucia Motlova, Gabriela Mikusova, Juraj Bosak, Kateiina Snopkova, David Smajs, Ivo Konopasek, Radovan Fiser
Summary: Fonticins are phage tail-like bacteriocins produced by the Gram-negative bacterium Pragia fontium. They can penetrate sensitive cells and form large pores. This research reveals the structural properties of Fonticins and their potential application as a nanodevice.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Chemistry, Medicinal
Abhishek Acharya, Ishan Ghai, Claudio Piselli, Jigneshkumar Dahyabhai Prajapati, Roland Benz, Mathias Winterhalter, Ulrich Kleinekathoefer
Summary: In this study, the molecular mechanism of an antibiotic permeating through a bacterial channel is revealed, with a focus on the role of conformational dynamics of the constriction loop. The dynamics of the L3 loop, specifically the F118 to S125 segment, at the constriction regions of the OmpF porin is investigated using temperature accelerated sliced sampling approach. The importance of hydrogen-bond stabilization in the conformational dynamics of the L3 loop is demonstrated through single channel electrophysiology experiments and applied-field simulations. The findings suggest that conformational dynamics of the constriction loop may play a general role in antibiotic permeation through porins.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Multidisciplinary Sciences
Frantisek Spoutil, Goretti Aranaz-Novaliches, Michaela Prochazkova, Tomas Wald, Vendula Novosadova, Petr Kasparek, Radim Osicka, Janne E. Reseland, Staale P. Lyngstadaas, Hanna Tiainen, Kristyna Bousova, Jiri Vondrasek, Radislav Sedlacek, Jan Prochazka
Summary: Highly specialized enamel matrix proteins (EMPs), essential for enamel maturation, have diverged from a common ancestral gene and exhibit non-canonical functions. To investigate their role, comprehensive phenotyping and data from the International Mouse Phenotyping Consortium were used to assess the impact of EMPs on various physiological systems. The results showed that the absence of amelogenin, ameloblastin, amelotin, and enamelin affected multiple functions, supporting the hypothesis that EMPs serve as general physiological regulators. The findings also demonstrated the influence of amelogenin and ameloblastin on bone physiology, highlighting the non-canonical function of EMPs in modern species.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Kevin Munoz Navarrete, Ladislav Bumba, Tatyana Prudnikova, Ivana Malcova, Tania Romero Allsop, Peter Sebo, Jana Kamanova
Summary: The study reveals that BopN is a gatekeeper of the Bordetella T3SS, responsible for regulating the secretion and translocation of the BteA effector into host cells. It is similar to gatekeepers that control access to the T3SS channel from the bacterial cytoplasm. Deletion of the bopN gene in B. bronchiseptica increased secretion of BteA, but decreased the translocation of BteA into host cell cytoplasm.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Giusto D. Badami, Marco P. La Manna, Paola Di Carlo, Ondrej Stanek, Irena Linhartova, Nadia Caccamo, Peter Sebo, Francesco Dieli
Summary: HLA-E-restricted CD8+ T lymphocytes play a critical role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. This study investigates the ability of the enzymatically inactive Bordetella pertussis adenylate cyclase (CyaA) toxoid to deliver HLA-E-binding Mtb epitopes for expanding human CD8+ T cells in vitro. The results demonstrate that the CyaA-toxoid containing HLA-E-restricted Mtb epitopes can significantly expand antigen-specific CD8+ T cells and promote interferon-gamma production and cytotoxic activity.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
L. Brazdilova, J. Holubova, O. Stanek, N. Klimova, L. Bumba, P. Sebo
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)