The Institute of Microbiology (IMicB) was founded in 1947 by Prof. Stephan Angeloff, Member of Bulgarian Academy of Sciences. Ever since, the Institute’s.

The Institute of Microbiology (IMicB) was founded in 1947 by Prof. Stephan Angeloff, Member of Bulgarian Academy of

Sciences. Ever since, the Institute’s strategic lines have been: (1) research on problems with implications in public health

and industrial use; (2) teaching activities and training of PhD students. In 2004, The Stephan Angeloff Institute of

Microbiology was accepted as associated member of the Pasteur Institute (Paris) family, the sixth associated institute in

Europe: a great recognition by this world centre of microbiology and molecular biology, a leader in the struggle

against infectious diseases.

The Institute has 11 departments and a staff of 170 including 4 professors, one of them Corresponding Member of BAS, 34 associate professors and 52 research scientists. Its expertise

areas are: morphology and ultrastructure, genetics, biochemistry, physiology and ecology of microorganisms,

mycology, virology, infectious microbiology and immunology.

In the recent years, IMicB has structured its research activity to reflect both European and national bioscience priorities.

The efforts are currently concentrated on some key practical problems of public health (tuberculosis, actual viral infections,

autoimmunity and autoimmune diseases, vaccines), drug design (screening and development of antivirals, antibiotics

and other antimicrobial agents, biological response

modifiers), food safety, biotechnology, and environmental protection.

Recent achievements include:

In the field of infectious bacteriology: Tuberculosis, emerging zoonotic diseases and food-borne infections as serious problems for

healthcare, agriculture and food industry are the principal topics. Molecular epidemiological investigation on pandemic tuberculosis spread in Bulgaria was

started within the frame of the Pasteur Institutes cooperation.

The case detection rate of multidrug-resistant tuberculosis is improved by molecular characterization of Mycobacterium tuberculosis strains.

Polymerase chain reaction (PCR) has been developed for rapid detection of food-born pathogens in meat, milk and their products. This highly specific and sensitive method allows detection of 1 to 10 bacterial cells per gram sample.

Effective control was carried out against Campylobacter, Salmonella, and Listeria from farm to dish. Enteric Yersinia species are selected for

development of new generation of live carrier vaccines (against swine pest). Bacteria are efficiently attenuated by targeted disruption of genes encoding

virulence factors. To assess the important role of vaginal lactobacilli in maintaining the vaginal health and in the prevention or therapy of bacterial vaginosis, a molecular-genetic study of vaginal lactobacilli from Bulgarian

women was carried out. Twenty-two active strains were identified and grouped according to their genetic relatedness, based on a combined approach which

included amplified ribosomal DNA restriction analysis (ARDRA), ribotyping and PCR with species-specific oligonucleotide primers.

In the field of virology: Antiviral agents – inhibitors of viral replication is the main topic of virological stuidies in the Institute with a leading position in European scale.

A large-spectrum antiviral screening system was developed resulting in discovery of a series of new prospective antiviral substances (mopyridone,

active vs. influenza and togaviruses, oxoglaucin – vs. enteroviruses, substances isolated from plants– vs. influenza viruses, etc.). The principal topics in antiviral investigations include: determination of the molecular mechanisms of action of

antivirals – viral proteins ligands (influenza virus M1 protein as a target of mopyridone, adenovirus hexon protein – of abitylguanide), the drug-resistance

phenomenon in enterovirus capsid-binding inhibitors as a barrier for the development of anti-enteroviral chemotherapy, the chemical structure – antiviral activity relationship. Several synergistic combinations of antivirals hihly efficient against enteroviruses, influenza A virus, herpesviruses and vaccinia virus have

been established. Cycluridine has been developed as an efficacious chemotherapeutic agent against flaviviruses, including pestivirus infections in

cattle. Role of oxidative stress in flu pathogenesis and protective effect of antioxidants were clarified. Efficacy of other biological response modifiers

(immunomodulators, proteolysis inhibitors) was proved. Systematic studies on virucidal microbicides resulted in the characterization of a new-type virucidal

agent for hand disinfection. Evidence on the role of hantaviruses in pathogenesis of the Balkan endemic nephropathy was obtained. Molecular

epidemiological study on human papillomaviruses as etiological agents of the cervical cancer in this country was realized. New proves on the role of

neurotropic viruses in the insulin-dependent diabetes mellitus (on a model of herpesvirus infection in organ culture of Langerhans islets) was presented.

In the field of infectious immunology:

The ability of the opportunistic yeast Candida albicans to induce reactive arthritis in normal and in predisposed individuals

has been studied. The relationship between infections and rheumatic diseases has been analyzed in detail with the aim to

propose new therapeutic approaches.The pathological autoreactive B lymphocytes in

autoimmune diseases are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells by using artificial molecules that cross-link their immunoglobulin- with the inhibitory

IgG Fc-gamma IIb receptors. A series of hybrid molecules has been constructed and shown to decrease specifically the

production of disease-associated IgG autoantibodies and to delay the development of systemic lupus erythematosus in mice. The

use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective

suppression of autoreactive disease-associated B cells in autoimmune diseases.

We have also worked on new therapeutic strategies in sepsis as there is an urgent unmet medical need for new

treatments for this disease. Our therapeutic approach consists of the conception, development and testing of improved

immunoglobulins with enhanced anti-inflammatory activity.

In the field of applied microbiology:

The Institute has always played a leading role in applied microbiology in Bulgaria and in the Central and South-East European areas. The most important attainments in this field are the development of effective technologies for production of industrial important biologically active substances – enzymes (proteinases, pectinases, glucoamylase, neuraminidase, superoxide dismutase, glucose isomerase, keratinase, -galactosidase, yeast protein phosphatases, etc.), amino acids, growth factors, polysaccharides, vitamins, carotinoids, and various antibiotics. A wide spectrum of methods for the immobilization of enzymes and microbial cells-producers of valuable products, were elaborated. The physiology and biochemistry of microbial producers, as well as the properties of the synthesized products were studied in detail. The efforts were focused also on characterization of microbial cell response against different types of environmental stress (oxidative stress, heat- and cold-shock, heavy metal toxicity); examination of mechanisms responsible

for microbial degradation of aromatic compounds (phenol and its toxic derivatives, methylstyren, acetone, benzoic acid, methanol, organic cyanides -nitriles) and genomic analysis of the aromatic catabolic pathways; microbial transformation of steroid compounds, resulting in intermediates for pharmacy and drugs; role of surface active compounds in the development of efficient technologies for bioremediation of polluted sites; identification of lactic acid bacteria from different ecological niches and the characterization of antimicrobial peptides (bacteriocins) produced.

The Institute’s scientists studied unique natural biosystems of lactic acid microflora and created multi-component symbiotic starters for wholesome dairy products of high nutritive value. The results contributed to the force of the Bulgarian trade mark.

New bacterial strains representing unknown phylogenetic units were isolated from Bulgarian hot springs. Many of them are producers of thermostable enzymes with huge biotechnological importance (nitrilase, gellan lyase, xylanase, lipase, cyclo-dextrin transferase, superoxide dismutase). A collection of psychrophilic, psychrotrophic and mesophilic microorganisms isolated from Antarctic samples provided by the Bulgarian Antarctic Expeditions at the Livingston Island and Arctic (Spitzbergen) was made. The biological potential and metabolic ability of selected strains (bacteria, actinomycetes, yeasts and fungi) were studied. New bacterial strains representing unknown phylogenetic units were isolated from Bulgarian hot springs. Many of them are producers of thermostable enzymes with huge biotechnological importance (nitrilase, gellan lyase, xylanase, lipase, cyclo-dextrin transferase, superoxide dismutase). A collection of psychrophilic, psychrotrophic and mesophilic microorganisms isolated from Antarctic samples provided by the Bulgarian Antarctic Expeditions at the Livingston Island and Arctic (Spitzbergen) was made. The biological potential and metabolic ability of selected strains (bacteria, actinomycetes, yeasts and fungi) were studied.

The educational activities of the Institute include: doctoral studies (35 PhD students within the last five years); training courses for young

scientists from the Balkan countries at the Atellie Institut Pasteur; participation in the Leonardo da Vinchi Programme of EC. Thirteen scientists

give lectures at nine Bulgarian universities.

Scientists from the Institute participate in scientific councils, editorial boards, councils of organizations and scientific societies in Bulgaria and

abroad (such as WHO, IUMS, FEMS, etc.).

IMicB is the initiator of the establishment of the Balkan Society for Microbiology, and is the head quarter of this society and the Bulgarian

Society for Microbiology.

Consultancy is provided for many institutions (governmental, university, private etc) about ecology and environment, public health,

agriculture and food industry. Scientists are included in the work of many expert groups among which , Expert Group on Countering the Effects of

Biological and Chemical Terrorism at EC, Permanent Commission for Prevention of the Population from Natural Disasters and Catastrophes, Expert Council for Epidemiological Control of Infectious Diseases and

Immunoprophylaxis, Commission for Eradication of Polyomyelitis at the Ministry of Public Health, National Agencies of Standardization and

Authorization.