Day 1 :
Colorado State University, USA
Keynote: The cell envelope of Mycobacterium tuberculosis and new drug discovery against tuberculosis
Time : 09:00-: 09:40
Patrick J Brennan was graduated from University College Cork, National University of Ireland with the degrees of BSc (1961) and MSc (1962) before arriving at Trinity College Dublin to undertake research, leading PhD degree (1965), on the mode of action of the anti-tuberculosis drug, Isoniazid, followed by a two year Postdoctoral Fellowship at the University of California (Berkeley) studying the structures and biosynthesis of the phosphatidylinositol mannosides of Mycobacterium tuberculosis. He has held Senior posts in the National Jewish Centre for Immunology and Respiratory Medicine and the University of Colorado, School of Medicine in Denver before being appointed as Associate Professor, Professor and ultimately University Distinguished Professor at Colorado State University. He has published more than 300 peer reviewed papers on tuberculosis and leprosy. He has served as Chairman of the World Health Organization Program for Tropical Disease Research; Research Advisor to the Sasakawa Memorial Health Foundation who, through the Nippon Foundation, underwrites most of the Global Leprosy Elimination Campaign and Chairman of the US-Japan Cooperative Medical Sciences Program.
Work of ours and others over the past 30 years has resulted in a thorough understanding of the structure of the mycobacterial cell wall and membranes but also the basic genetics and biosynthesis, providing essential targets for new drug development and molecular rationale for the bactericidal action of established antibiotics. The enzymology and underlying genetics of fatty acid and mycolic acids synthesis are well known and with it the mode of action of isoniazid, ethionamide, thiocarlides, thiolactomycin, etc. There is now convincing evidence that intercalated within this mycolic acids lipid environment are those ‘special’ (glycol) lipids; the phthiocerol dimycocerosates cord factor/dimycolyltrehalose, the sulfolipids, the phosphatidylinositol mannosides, etc., to form a true outer membrane (OM). Mycobacterial genetics and the creation of transposon and targeted mutant libraries has allowed definition of the synthesis of all of these entities, invaluable in comprehension of their roles in disease pathogenesis and aspects of the immune response; however, their general non-essentiality for bacterial growth limits their usefulness as targets for new drug development especially to counteract MDR-TB. The massive essential cell wall "core" of M. tuberculosis is comprised of peptidoglycan covalently attached via a linker unit (L‑Rha‑D‑GlcNAc‑P) to a linear galactofuran composed of Galf units, in turn attached to several strands of a highly branched arabinofuran (Araf), in turn attached to the mycolic acids. Definition of the genome of M. tuberculosis has greatly aided efforts to define the biosynthetic pathways leading to assembly of this cell wall core. Over the past 10 years we have painstakingly defined the essential enzymes in each of these pathways by knock-out and conditional mutagenesis and targeted the enzymes (e.g., all enzymes in the Rha synthetic pathway; the Galp mutase, the Galf and Araf transferases) by high and medium throughput screening of compound libraries. Yet, no promising leads have arisen from these efforts. Yet, the pursuit of interesting chemical entities by the research community, directly or via synthetic modifications has yielded some of the most promising lead compound now in our new drug armament. Examples are: the benzothiazinones, dinitrobenzamides and ethambutol inhibiting aspects of arabinan synthesis; CPZEN-45 inhibiting synthesis of the linker unit; the diarylquinolones and benzophenones addressing electron transport; thioureas inhibiting aspects of fatty acid synthesis; substituted triclosan derivatives and the nitroimidazoles inhibiting aspects of mycolic acids synthesis and several diamines involved in inhibition of the translocation of mycolic acids. These developments and others will be discussed in the context of current approaches to exploit our unprecedented knowledge of the biogenesis of the cell wall and membranes of M. tuberculosis for purposes of producing new and safe chemical scaffolds to address tuberculosis in its various aspects.
Comenius University, Slovakia
Keynote: The role of biofilm, the super virulence factor in pathogenicity of the yeasts from the genus Candida
Time : 09:40- 10:20
Helena Bujdakova is the Head of the Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Slovakia and Vice President of the Czechoslovak Society for Microbiology. She has received Fulbright and JSPS scholarships for research/teaching stays in USA and Japan. She is a Specialist in Medical Microbiology, her current research is focused on various topics dealing with microbial biofilms, especially, aimed at yeasts of the genus Candida. She has published more than 60 articles indexed in reputed databases.
Biofilms formed by Candida species (spp.) are a heterogeneous community of cells adhering to various surfaces (biotic and abiotic) and surrounded by an extracellular matrix. These yeasts are able to form biofilms on medical devices that can be a source of the life-threatening infections. The most frequent Candida isolated from clinical material is Candida albicans, but non Candida albicans spp., like Candida parapsilosis are on the rise. Generally, biofilm can be assumed to be the “super” virulence factor, as it represents a set of particular virulence factors that cooperate and assist each other. Moreover, resistance to conventional drugs manifested in biofilms is an important supporting virulence factor. The switching from the yeast to the mycelial form is an important feature of biofilms formed by already mentioned Candida spp. Both morphological forms co-exist together and dominant position of one or other is usually dependent on environmental stimuli, but also on elevation of quorum sensing molecules. The cell surface hydrophobicity is the phenomenon affected by the organization of the cell wall and it is also dependent on the physicochemical parameters of environment. Hydrophobicity directly participates in adherence which is the critical step in biofilm formation. Adherence is also associated with an expression of different adhesive molecules, for example, those from ALS (agglutinin-like sequences) family or other “mimicry” proteins triggering the host immune response. The current challenge concerning the study of microbial biofilms is focused on understanding the key virulence factors “hand in hand” with searching for new options in biofilm eradication.
University of Valencia, Spain
Time : 10:20- 11:00
Amparo Gamero Lluna works as an Assistant Professor in Nutrition & Bromatology area at the University of Valencia, Spain and holds a European PhD in Food Science, Technology and Management. Her main research topic is the study of yeast fermentations. She has a wide range of publications and contributions to international conferences. She has worked and carried out short stays at different universities, research centers and companies of different countries.
Selected Saccharomyces cerevisiae strains are currently used for the manufacture of products such as bread or alcoholic beverages in order to assure process control and homogeneity of the product. Nevertheless, some other products are produced through traditional or spontaneous fermentations in which no starter is added. Additionally, in certain food sectors such as wine making, there is an increasing demand for isolation and selection of autochthonous flora in order to maintain traditional organoleptic properties of the region. In this context, it is crucial to explore the ecology of the fermented products experiencing spontaneous fermentations as well as the properties that those microorganisms have in terms of the development of desirable sensorial attributes. The yeast domain contains around 2000 other species different from S. cerevisiae, which some of them are poorly studied but present a huge potential to be used in industrial fermentations due to their huge diversity of properties, some of them still unknown. Yeasts are able of carrying out alcoholic fermentation, but they can intensely affect aroma and other organoleptic properties of the resulting fermented products as well. Through the study of those properties, novel applications of yeast in food products may arise, thus enriching the diversity of the products coming from the food industry.