Day 1 :
University of Illinois College of Medicine, USA
Time : 09:45-10:30
Dr. Ananda M. Chakrabarty serves as Senior Science Advisor of Amrita Therapeutics Limited. Dr. Chakrabarty is a Amrita’s Senior Science Mentor and Global Domain Expert relating to how bacterial proteins effectively combat cancers, parasites, and viruses in the human body. Dr. Chakrabarty serves as a Distinguished University Professor of Microbiology and Immunology at the University Of Illinois College Of Medicine, and advises senior officials in the U.S. and abroad on policies relating to biotechnology and related technology transfer. He is a Consultant to the United Nations. In 1980, Dr. Chakrabarty’s genetically modified Pseudomonas bacteria became the first genetically-engineered organism to gain a patent, as a result of the Supreme Court decision in Diamond vs. Chakrabarty. Dr. Chakrabarty undertook pioneering biotechnology research into the therapeutic potential for protein products of bacteria, both at the University of Illinois at Chicago (UIC) and on behalf of CDG Therapeutics, a U.S. biotechnology start-up company engaged in clinical cancer research. Dr. Chakrabarty has led path-breaking research into the therapeutic qualities of protein products of bacteria. His work includes recent studies with water-soluble products of pathogenic bacteria demonstrating significant promise for cancer therapies, effective against HIV/AIDS, malaria and perhaps even tuberculosis. Dr. Chakrabarty was a part of the Advisory Committee that resulted in creation of the International Center for Genetic Engineering and Biotechnology (ICGEB) in Trieste, Italy and rejoined the ICGEB Advisory Board. Dr. Chakrabarty has numerous publications and has received many notable awards for his contributions to biotechnology, including Padma Shri in 2007, one of the Indian Government’s highest civilian honors.
It is widely recognized that many bacteria can fight a variety of human diseases and indeed the American Academy of Microbiology convened an interesting meeting in 2014 in San Diego on the topic ‘Bugs as Drugs’, emphasizing the important role that bacteria play in fighting various diseases. The recent emphasis in this regard involves the role of human microbiome comprising of bacteria, archaea, fungi and protozoa, whose number is 10 fold higher than the human cells themselves. Many such gut bacteria have been implicated in immune modulation and protection of the human body from attacks by external pathogens. However, the disease-fighting role of pathogenic bacteria goes back more than 100 years when in 1892-93, William Coley in New York City’s Memorial Hospital observed that bacterial infections of his cancer patients often led to tumor regression. Since then, many efforts have been made and are continually being made to use genetically-modified bacteria to fight cancer, but only with limited success in the clinical trials because of the elimination of the cancer fighting bacteria by the patient’s immune system. Our efforts have not been directed to live bacteria but protein products of pathogenic bacteria such as Pseudomonas aeruginosa. One such cancer fighting protein, azurin has shown significant tumor regression in mice. Since proteins are designated as biologics and thus requiring undergoing stringent regulation by the USFDA for clinical trials, a company CDG Therapeutics, Inc., has used a fragment of azurin termed p28, a peptide of 28 amino acids for both pre-clinical and phase-I clinical trials. P28 showed no toxicity in a variety of animals, whereupon the FDA approved a phase-I trial of p28 in 15 stage-IV cancer patients with solid tumors such as melanoma, colon, sarcoma, prostate and pancreas. These tumors were resistant to all conventional drugs and the patients were terminally ill with a life expectancy of about 6 months. When administered through intravenous injections, p28 demonstrated very little toxicity but significant beneficial effects including partial and complete regression of these drug resistant tumors in 4 patients. Encouraged by such results, the National Cancer Institute (NCI) sponsored a second phase-I trial in 11 major hospitals in the US in pediatric brain tumor patients in October, 2013. That trial has been on-going for more than 2 years suggesting that p28 not only demonstrated acceptable toxicity but significant regression of the tumors in some patients. Indeed, it is important to note that the USFDA has approved on December 02, 2015, the designation of azurin-p28 as an orphan drug for the treatment of brain tumor glioma. Another company Amrita Therapeutics in India has developed similar bacterial peptides as potential anticancer drugs, indicating the role that bacterial proteins/peptides can play in cancer therapy.
University of Notre Dame, USA
Keynote: Interactions between Streptococcus pyogenes and the host innate immune system that promote bacterial virulence
Time : 10:30-11:15
Francis J Castellino has received his PhD degree in Biochemistry from the University of Iowa and spent two Postdoctoral years at the Duke University School of Medicine. He is the Kleiderer-Pezold Professor of Biochemistry and Director of the prestigious Keck Center for Transgene Research at the University of Notre Dame. He has published over 450 peer reviewed papers in the structural biochemistry of components of blood coagulation, anticoagulation and fibrinolysis, as well as in the pathophysiology of infective and inflammatory diseases related to hemostasis. He is a Member of several journal Editorial Boards and is the Editor-In-Chief of Current Drug Targets.
Approximately 250 M-protein based serotypes of Gram+ Group A Streptococcus pyogenes (GAS) have been isolated from infected patients. These isolates range from mild antibiotic-sensitive infections of the skin and nasopharynx to highly virulent infections of deep tissue that lead to conditions such as toxic septic shock and necrotizing fasciitis, as well as post-infective sequelae that include glomerulonephritis and rheumatic heart disease. A constant battle for survival is waged between this highly honed human-specific bacterium and the human host that can only employ generalized defense systems to combat the spread of the organism. GAS has evolved survival systems that include regulation of its own gene expression by sensors of different environmental niches, along with secretion of exotoxins that combat host defense cells and of great importance to this discussion, utilization of normal host systems for its defense. Of special interest is the conscription of the human hemostasis system by certain strains of GAS to aid this microbe in its survival and dissemination. Mechanisms will be discussed whereby components of the human coagulation, fibrinolytic, complement and inflammation systems are employed by GAS for its survival benefit.
Université catholique de Louvain, Belgium
Keynote: Are public campaigns effective to reduce antibiotic overconsumption: Did we fail to provide what is needed by the general practitioner?
Time : 11:35-12:00
Paul M Tulkens has completed his MD from the Université Catholique de Louvain, Belgium. He has obtained his Postdoctoral studies from Rockefeller University, New York. He has created the Unit of Cellular and Molecular Pharmacology and has also launched the activities of Clinical Pharmacy at the Université Catholique de Louvain. He has published more than 280 papers in reputed journals and has been serving as an Editorial Board Member of several journals dealing with antibiotics.
Overconsumption of antibiotics is a major cause of increased bacterial resistance especially in the community. In the late 1990's, it became evident that the sales of prescribed antibiotics in the community in Belgium far exceeded that of other EU countries, largely due to patients' pressures. Accordingly, a public campaign was launched in 2000 (key message: "Do not ask for an antibiotic for non-bacterial infections") and repeated each year until now. The first campaigns (2000-2001 and 2001-2002) caused a significant reduction in antibiotic use (expressed in daily Defined Daily Doses [DDD] per inhabitant and per year). However, no further decrease but an increase was seen all over the 2003 to 2013 period. In parallel, focus groups studies with general practitioners, in-depth analysis of prescriptions habits through interviews with prescribers and national questionnaire studies showed that the main reasons for overprescribing antibiotics were the lack of early and unambiguous causal diagnostic (viral vs. bacterial infection), the pressure of patients when in need of a fast relief and the prescriber's fear of complications if not prescribing an antibiotic coverage. We conclude that public campaigns for reducing antibiotic over prescription in the community are not effective in reducing antibiotic consumption because they do not address the real causes of the prescriber's deviation from the proposed guidelines. Efforts should be directed towards definite improvements in early diagnostic and in the setting up of effective prevention measures about potential complications of infections for which no antibiotic would have been prescribed as per the guidelines.