Day 1 :
Yokohama University of Pharmacy, Japan
Keynote: EFdA: An extremely excellent anti-HIV nucleoside from design to the current clinical trial results
Time : 10:00-10:30
Hiroshi Ohrui has completed his PhD in Organic Chemistry at the University of Tokyo and Postdoctoral studies at Sloan-Kettering Institute for Cancer Research and Syntex Research. He has worked at Riken and Tohoku University and received several awards including The Japan Society for Analytical Chemistry Award and Japan Academy Prize.
EFdA (4’-C-ethynyl-2-fluoro-2’-deoxyadenosine) prevents the emergence of resistant HIV mutants, is over 400 times more active than AZT and several orders of magnitude more active than other clinical reverse-transcriptase inhibitory 2’, 3’-dideoxynucleoside drugs, very low toxic, very long acting, and very useful for prophylaxis. EFdA is now under clinical investigation by Merck & Co. as MK-8591. In the beginning, a general idea for the development of anti-viral modified nucleosides is presented. Next, the development of EFdA is discussed and then the current clinical trial results by Merck will be presented. For the development of EFdA, four working hypotheses, the way to prevent the emergence of resistant HIV mutants, the way to decrease the toxicity of nucleosides, the way to provide nucleoside with stability for long acting, the difference of the substrate selectivity between human and viral nucleic acid polymerases makes it possible to develop very excellent anti-viral modified nucleosides, were proposed. 4’-C-substituted-2’-deoxy nucleoside (4’SdN) was designed as the nucleoside which could satisfy these hypotheses. The study on 4’SdN has successfully resulted in the development of EFdA.
Karadeniz Technical University, Turkey
Keynote: Antibacterial properties of three newly identified recombinant Staphylococcus aureus phage endolysins
Time : 10:30-11:00
Ali O Kilic has completed his PhD at Oklahoma State University in Microbiology and Molecular Genetics in 1994, and Postdoctoral studies from University of Missouri-Kansas City. He worked as Res. Assist. Prof. at the Collage of Dentistry, University of Illinois at Chicago, as a project manager of Healthcare Domain at Air Liquide, and as a senior group leader at Vaccines and Biologics department of Pharmaceutical Product Development for ove ten years. He has published more than 30 papers in reputed journals and has been working as full-time faculty member at School of Medicine, Karadeniz Technical University since 2013.
Staphylococcus aureus causes serious infections in humans and animals. Controlling of staphylococcal infections is becoming very difficult to due to the emergence of multidrug-resistant strains. Therefore, search for novel antimicrobial alternatives has become of great importance. One of these new approaches is bacteriophage-encoded endolysin enzymes, which have exogenous lytic activity against multiple antibiotic resistant bacteria, especially in Gram positive bacteria. In this study, we described cloning, expression and functional analysis of three endolysins from temperate bacteriophages from three clinical isolates of S. aureus strains. Temperate phages were isolated from the host strains using the mitomycin C induction. The endolysin genes of the phages were amplified using PCR, cloned and over-expressed in E.coli. The lytic activity of endolysins were tested against a wide range of bacterial species using spot-on-lawn assay method. The combination of the three endolysins (LysSA10, LysSA14 and LysSA15) displayed activity against 222 of 239 (93%) of S. aureus strains including 67 MRSA and 6 ATCC type strains. In addition, endolysins showed lytic activity against other Gram positive bacteria including a number of clinical and type strains of S. epidermidis, S. haemolyticus, Enterococcus faecalis, E. faecium, Streptococcus pyogenes, S. pneumoniae, S. intermedius, Bacillus subtilis, and B. atrophaeus. No lytic activity was observed against 7 Lactobacillus and one Listeria monocytogenes ATCC type strains tested.Overall, our results showed that the combination of the newly identified three recombinant endolysins exhibited a broad host range against several Gram positive bacteria. Thus, these endolysins are promising antimicrobial agents for combating bacterial pathogens.