Host-parasite relationship

The research group consists of different fields of medical microbiology and immunology. Fields are linked by investigation of molecular epidemiology and ecology, and by study of genetic variability and pathogenesis of particular microorganisms. The aim of the research is to establish modes of transmission and spreading and to determine factors that influence the pathogenicity and the treatment of the diseases included in the study. BACTERIOLOGY: mechanisms of bacterial resistance, epidemiology and pathogenesis of infections will be studied. In carbapenem-resistant gram-negative bacteria, porin changes will be studied in addition to carbapenemases. In ESBL-producing E. coli, the virulent clones and the groups of enzymes will be identified. In ESBL carriers, the sites and duration of colonization and carriage clones will be investigated. Genetic heterogeneity and virulence factors of CA-MRSA will be determined. Genetic heterogeneity and pathogenesis of M. pneumoniae will be investigated. IMMUNOLOGY: we will focus on the microbial pathogenesis and disease expression in immunocompromised host (IC). Our goal is to study specific immune characteristics in IC hosts and immunopathogenetic characteristics of most common infectious agents occurring in IC patients (fungal, protozoan, bacterial and viral). VIROLOGY: in investigation of different neoplasms of the skin and mucosa we expect to clarify whether these tumors are caused by specific, more pathogenic HPV6/11 variants or whether tumor development is the consequence of a specific genetic background of the host and/or viral integration into specific region(s) of the human genome. In the field of enteric viruses we will focus on emerging rotavirus genotype variability and on norovirus molecular epidemiology, as new genetic lineages emerge. While in respiratory viruses we intent to determine, whether the incidence and severity of the clinical presentation is linked to specific viral strains. In research of viral hemorrhagic fevers (VHF), we intend to expand our knowledge on the pathogenesis of VHFs, with determining the degree of activation of the innate immune response, particularly type I interferon response, and hosts genetic factors involved. ZOONOSES: we plan to outline the risks of spreading the disease and the occurrence of zoonotic agents, thus we will focus on the development of modern diagnostic methods, study of hosts and vectors, and on the development of predictive maps. With an extensive epidemiological and ecological investigation we will address the prevalence of vector borne zoonotic agents, such as: Borrelia, Leptospira, Ehrlichia/Anaplasma, Francisella, TBEV, HNTV, WNV, fleboviruses, Giardia sp…. In addition, the aim of the research is to establish a national biobank of isolates, which would enable accurate genotyping, discovery of new genetic lineages and their zoonotic reservoir.

BACTERIOLOGY Porin changes in carbapenem-resistant gram-negative bacilli are relatively unknown and our study will enhance the knowledge in this area. Results of study on colonization with ESBL-producing enterobacteria will enhance knowledge on duration, predilection sites and factors that influence the period of colonization. With the description of virulent clones and their enzymes, the cause for increase of these infections will be explained. With the investigation of CA-MRSA from the Slovenian collection, we will be able to detect increases in the prevalence, the differences between colonizing strains and strains causing infections and to assess their presence in hospitals. Investigation of M.pneumoniae pathogenesis will determine whether there are differences in virulence and cytokine production stimulation among different genotypes. IMMUNOLOGY Our research will focus on infections in patients with congenital immune deficit diseases, which will be phenotypically and genetically characterized [agammaglobulinaemia, common variable immunodeficiency (CVID)]. In immunodeficient patients we will analyse cellular and molecular mechanisms important for antifungal defense. Our research will thus contribute to a better understanding of the pathogenesis of fungal diseases and to the improvement of antifungal therapies and vaccines. Furthermore, the results of the proposed program will be of great importance for our future research of fungal respiratory diseases. VIROLOGY Characterization of novel HPV types can contribute to better understanding of viral pathogenesis and diseases associated with HPV, assessment of general diversity and phylogenetic relationships of HPVs, improvement of viral diagnostics and development of new HPV vaccines. Molecular analysis of HPV6/11 related malignant tumors will significantly contribute to the general understanding of low-risk HPV mediated carcinogenesis. Output of our research in the field of enteric virus epidemiology will contribute to the explanation of virus evolution, which is the basis for the upgrading research in the field of pathogenesis, development of effective vaccines and antiviral agents and improvement of diagnosis. ZOONOSES Predictive maps will identify the main ecological and anthropological factors associated with the increase in HFRS incidence, thus providing a groundwork for preventive measures. The developed predictive models will also be employed in neighboring countries, since zoonoses spread according to environmental obstacles and not national boundaries. We will develop modern diagnostic methods, available to scientists in Slovenia and around the world. The development of a national biobank, of samples and pathogens, is crucial for both basic and applied research, enabling accurate diagnosis and genotyping, discovery of new agents and genotypes, and last but not least allowing a rapid exchange of information.

BACTERIOLOGY Results of the prevalence studies of colonization with ESBL-producing enterobacteria will provide a basis for the development of effective recommendations for infection control. Namely, current knowledge and recommendations are inadequate or absent. With the timely detection and expanded knowledge about CA-MRSA effective public health for prevention of nosocomial infections will be enabled. Use of novel molecular and antigen detection methods will improve diagnostics of bacterial and fungal infections, thereby enhancing antimicrobial therapy and facilitating a positive outcome of the treatment. IMMUNOLOGY In recent decades the incidence of fungal infections is increasing, especially among immunocompromised patients. In our study we will examine the interaction between different species of Candida spp. and host inflammatory cells and try to determine how the immune response affects the progress and the output of these infections. Our results will provide extensive knowledge about the immunological processes and will enable an improved clinical evaluation and treatment of these infections. VIROLOGY In the study of low-risk HPV mediated carcinogenesis, deep sequencing technology will be used for the first time, together with several novel bioinformatics approaches. This will significantly impact the progress and the level of research and engineering practice in Slovenia. The rational diagnosis of viral infections will enable a timely diagnosis of epidemics in the environment and within health and institutional care unit, which can significantly impact morbidity, mortality, rational use of antimicrobial agents and direct costs associated with the treatment of patients. Strain surveillance will contribute valuable data to the local database. Together with the establishment of standard protocols for the detection of viruses in diseases of unknown etiology, the establishment and further development of the most successful diagnostic center in Slovenia will be enabled. Viral hemorrhagic fevers pathogenesis studies will determine the possibility of registered drug use in treatments of severe disease forms of VHFs. ZOONOSES Our research will improve data on prevalence and emergence of zoonotic pathogens in Slovenia and will enable evaluation of the individual risk assessment for specific pathogens. A focused public awareness campaign and effective outbreak prevention and control will be supported, providing a significant benefit to public health and will help to reduce costs. We also aim to create a biobank of viral isolates of pathogens, present in Slovenia. Viruses and viral products will be disseminated in the scope of the European project EVA to other research or public health institution in Europe and beyond.