Showing papers by "Jiri Stulik published in 2015"
TL;DR: Results show that vaccination with ΔdsbA/F SC200 mutant, but not ΔiglH/FSC200 mutants, induces an early innate inflammatory response leading to strong Th1-like antibody response, and elicited protection against the subsequent challenge with type A SCHU S4 strain in mice.
Abstract: Francisella tularensis subspecies tularensis is a highly virulent intracellular bacterial pathogen, causing the disease tularemia. However, a safe and effective vaccine for routine application against F. tularensis has not yet been developed. We have recently constructed the deletion mutants for the DsbA homolog protein (ΔdsbA/FSC200) and a hypothetical protein IglH (ΔiglH/FSC200) in the type B F. tularensis subsp. holarctica FSC200 strain, which exerted different protection capacity against parental virulent strain. In this study, we further investigated the immunological correlates for these different levels of protection provided by ΔdsbA/FSC200 and ΔiglH/FSC200 mutants. Our results show that ΔdsbA/FSC200 mutant, but not ΔiglH/FSC200 mutant, induces an early innate inflammatory response leading to strong Th1-like antibody response. Furthermore, vaccination with ΔdsbA/FSC200 mutant, but not with ΔiglH/FSC200, elicited protection against the subsequent challenge with type A SCHU S4 strain in mice. An immunoproteomic approach was used to map a spectrum of antigens targeted by Th1-like specific antibodies, and more than 80 bacterial antigens, including novel ones, were identified. Comparison of tularemic antigens recognized by the ΔdsbA/FSC200 post-vaccination and the SCHU S4 post-challenge sera then revealed the existence of 22 novel SCHU S4 specific antibody clones.
13 citations
TL;DR: Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients.
Abstract: Background. Hypertrophic cardiomyopathy (HCM) is mostly autosomal dominant disease of the myocardium, which is characterized by myocardial hypertrophy. Vascular endothelial growth factor (VEGF) is involved in myocyte function, growth, and survival. The aim of study was to analyze the clinical significance of VEGF in structural and functional changes in patient with HCM. Methods. In a group of 21 patients with nonobstructive HCM, we assessed serum VEGF and analyzed its association with morphological and functional parameters. Compared to healthy controls, serum VEGF was increased: 199 (IQR: 120.4–260.8) ng/L versus 20 (IQR: 14.8–37.7) ng/L, . VEGF levels were associated with left atrium diameter (, ), left ventricle ejection fraction (, ), fractional shortening (, ), left ventricular mass (, ), LV mass index (, ), vena cava inferior diameter (, ), and peak gradient of tricuspid regurgitation (, ). Conclusions. Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients.
5 citations
TL;DR: A bacterial strain with deletion of the DSBA-like domain led to high in vivo attenuation associated with the ability to induce host protective immunity and it was proposed that for the correct FTS_1067 protein function both domains are needed.
Abstract: Francisella tularensis the etiological agent of tularaemia is one of the most infectious human pathogen known. Our knowledge about its key virulence factors has increased recently but it still remains a lot to explore. One of the described essential virulence factors is membrane lipoprotein FTS\_1067 (nomenclature of F. tularensis subsp. holarctica strain FSC200) with homology to the protein family of disulphide oxidoreductases DsbA. Lipoprotein consists of two different domains: the C-terminal DsbA\_Com1-like domain (DSBA-like) and the N-terminal FKBP-type peptidyl-prolyl cis / trans isomerases (FKBP\_N-like). To uncover the biological role of these domains, we created bacterial strain with deletion of the DSBA-like domain. This defect in gene coding for lipoprotein FTS\_1067 led to high in vivo attenuation associated with the ability to induce host protective immunity. Analyses performed with the truncated recombinant protein showed that the absence of DSBA-like domain revealed the loss of thiol/disulphide oxidoreductase activity and, additionally, confirmed the role of the FKBP\_N-like domain in the FTS\_1067 oligomerization and chaperone-like function. Finally, we verified that only full-length form of FTS\_1067 recombinant protein possesses the isomerase activity. Based on our results, we proposed that for the correct FTS\_1067 protein function both domains are needed.
3 citations