Day 1 :
University of Illinois at Chicago, USA
Ananda M Chakrabarty is a Distinguished University Professor at the University of Illinois at Chicago College of Medicine. His research interest involves development of promiscuous bacterial protein/peptide drugs with anticancer, anti-viral and anti-parasitic activities. He is the Co-founder of two start-up companies, CDG Therapeutics Inc., in Chicago and Amrita Therapeutics in India.
It is widely recognized that anticancer drugs are pricey and often involve intravenous injections, thus limiting their usefulness and affordability to people in rich countries. People in poor countries or people living in rural areas often do not have access to potent anticancer drugs. Our efforts have been directed to protein products of pathogenic bacteria such as Pseudomonas aeruginosa for potential cancer treatment. One such cancer fighting protein, azurin, has shown significant tumor regression in mice. Since proteins are designated as biologics, and thus requiring to undergo stringent regulation by the USFDA for clinical trials, a company, CDG Therapeutics, Inc. (www.cdgti.com) 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 9 major hospitals in the US in pediatric brain tumor patients in October, 2013. That trial has been on-going for more than 2 years (http://clinicaltrials.gov/ct2/show/NCT01975116) 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 (www.amritatherapeutics.com) has developed similar bacterial peptides as potential anticancer drugs, indicating the role that bacterial proteins/peptides can play in cancer therapy. Additionally, azurin gene has been cloned and expressed in plant cells. Oral consumption of such azurin-expressing plant extracts by mice allows tumor regression in tumor-bearing mice, demonstrating the potential usefulness of plant-expressed bacterial anticancer proteins in future cancer therapy.
US Army Medical Research Institute of Infectious Diseases, USA
Time : 11:30-12:15
Kei Amemiya is a Principal Investigator in the Bacteriology Division at the US Army Medical Research Institute of Infectious Diseases. He has been at USAMRIID since 1999 and has been involved in developing vaccine candidates against plague, glanders and melioidosis. His interest is in studying the host’s immune response to the pathogen and vaccines in small and large animal models. Before coming to USAMRIID, he was at the National Institutes of Health and Georgetown University, where he was studying the host response to bacterial and viral pathogens or autoimmune diseases in humans.
|There are many new and emerging diseases that are yet to be understood in regards to host-pathogen interactions, which makes effective treatment against these diseases still far in the future. Two emerging diseases that fall into this category are caused by Burkholderia pseudomallei and B. mallei, which are responsible for the diseases melioidosis and glanders, respectively. Although these two organisms are closely related, they exhibit differences in inducing the host innate immune response and interaction with specific hosts. For the past few years, we have been assessing different small and large animals to establish a model for melioidosis and glanders that would be suitable for evaluating candidate vaccines and therapeutic countermeasures against these two diseases. We have been examining the more sensitive BALB/c mouse and more resistant C57BL/6 mouse to their susceptibility to be infected by different strains of the pathogens. In addition, we have also been evaluating several species of nonhuman primates that could potentially serve as large animal models for melioidosis and glanders. We will discuss the possible benefits of selecting the small and large animal models for these two emerging diseases for evaluating future candidate vaccines and therapeutic countermeasures.|
Dr Rath Research Institute BV, USA
Anna Goc obtained her MS and PhD from the Jagiellonian University, Cracow, Poland. She has carried out her Postdoctoral training at Case Western Reserve University, Cleveland, OH, and the University of Georgia, Athens, GA. She also worked as a Research Biologist at the VA Medical Center, Augusta, GA. Currently she is working as a Head of Infectious Diseases Division at Dr. Rath Research Institute, Santa Clara, CA and she leads a lyme disease project. She has published over 30 peer-reviewed publications, two book chapters, and has presented her research at numerous national and international scientific meetings. She is also an active member on one Editorial Board and the recipient of several national and international awards.
Lyme disease is a multi-systemic bacterial infection transmitted by ticks that has emerged as the most common vector-borne disease in the USA and Europe. Current antibiotic therapies are associated with the well-known side effects and are not fully effective, especially against its persistent form, which calls for the development of new treatments. Naturally derived substances that are safe and if properly combined, could have enhanced efficacy through their synergistic or additive interactions, may serve as an alternative way for infected patients. Over 50 non-synthetic plant-derived compounds and extracts were tested in vitro individually and in combinations against active and persistent forms of B. burgdorferi (prevalent in US) and B. garrini (prevalent in Europe). Several of these compounds individually and in combinations showed high efficacy in eliminating all pleomorphic forms of studied Borrelia spp. In vivo results revealed that this defined combination of the most active compounds is effective in ~80% of clearing infection, while pre-clinical human study confirmed that this defined composition may play an important role in combating Borrelia spp. and serves as an adjunct or alternative treatment. The study reported here is a part of an ongoing pre-clinical development plan that could form the basis for clinical trials.
- Track 1:Bacterial Morphology and Metabolism | Track 2:Bacterial Clinical Studies | Track 4:Emerging Infectious Diseases | Track 5:Bacterial Pathogenesis | Track 7:Multi Pathogen Infections | Track 8:Microbial Genomics | Track 9:Industrial and Applied Bacteriology
Tata Institute of Fundamental Research, India
Shobhona Sharma has been exploring various aspects of the malaria parasite over several years at the Tata Institute of Fundamental Research, Mumbai, India. One of the major focuses of her lab has been the study of acquired immunity to malaria. Through a differential immunoscreen using sera samples from Eastern India, her group identified several novel protective malarial proteins. Of these, she has studied the structure and novel functions of Plasmodia ribosomal P-proteins extensively. Her metabolic monitoring of disease progression provides understanding of certain biochemical signatures. In collaboration with pharmacologists, her group also explores nanolipid carrier-mediated delivery of antimalarials. Recent results have shown that nano-lipid-carrier mediated delivery of antimalarial drugs and specific antibodies holds great promise in malaria control.
Malaria parasites reside inside erythrocytes and the disease manifestations are linked to the growth inside infected erythrocytes (IE). We have recently shown an involvement of a Plasmodium falciparum 60S stalk ribosomal protein P2 (PfP2), which gets exported to the IE surface for 6-8 hours during early schizogony, concomitant with functional amyloid-like SDS-resistant oligomerization. Treatment with anti-PfP2 monoclonal arrested Plasmodium at the onset of cell division. Here we report structure-function studies on purified recombinant PfP2-tetramer. NMR studies of PfP2-tetramer showed that the N-terminal domain forms a hydrophobic pocket, while the C-terminal stretch of 40 residues remains disordered. How does PfP2 anchor on the infected red cells? NMR studies of PfP2-tetramer in the presence of erythrocytes showed specific protease-sensitive binding of several C-terminal residues of PfP2 with erythrocytes, and no other cell type. Pull-down experiments using intact red blood cells have showed that the N-terminal domain was sufficient to bind to the red cells. Antibodies against P2 protein were found to block lipid uptake, disrupt the parasite-induced tubulovesicule network and restore the cell flexibility. The intriguing question pertains to the role of the IE surface exposed oligomer P2 protein. Does it work as a cell division check-point protein and sense the external milieu for specific serum components? Our results indicate that P2 protein does bind to very specific lipid moieties in an oligomer specific manner. Thus, the unique surface properties of PfP2 ribosomal protein is novel, and given that it is exposed to the immune system, it may be targeted to impair the growth of the parasite.
AyuVis Research LLC, USA
Dr. Suchi Acharya has more than 15 years of pharmaceutical drug discovery, development, pre-clinical, clinical and regulatory affairs experiences from Novartis and Alcon Research. She is the founder and CEO of AyuVis Research. She is also the lead inventor of the underlying this small molecule technology and the PI of the SBIR grant sponsored by NIAID/NIH. She is an experienced investigator and also holds Research Assistant Professor position in UNT Health Science Center, Fort Worth, Texas.
Intra-abdominal infection (IAI) is an important cause of morbidity and mortality. It is the second most commonly identified cause of severe sepsis in the intensive care unit (ICU). Recent studies have associated severe intra-abdominal infection with a significant mortality rate.
Most IAI are a result of processes involving inflammation and perforations of the gastrointestinal tract, such as appendicitis, peptic ulcer disease, and diverticulitis. Patients with diffuse peritonitis may be due to spontaneous perforation, post-operative, post-interventional or post-traumatic causes. The lower GI tract is most often the location of perforation. Among patients with IAI who develop peritonitis, many may progress to severe sepsis, defined by The American College of Chest Physicians/Society of Critical Care Medicine as a severe systemic inflammatory response to infection that is associated with acute organ dysfunction.
AyuVis Research’s overarching goal is to develop and commercialize a small molecular weight, water soluble, compound useful in adjunctive and/or in combination therapy via intravenous (IV) dosing for complicated intra- abdominal infection that may lead to sepsis.
We have reported a novel approach to treat secondary or tertiary peritonitis leading to sepsis and death fundamentally different from other reports. This multi-functional small molecule AyuV-25 by virtue of its ability to bind to the active sites of TLR4 can competitively inhibit LPS induced inflammation as well as produce alternately activated macrophages leading to organ protection and tissue repair. Preliminary results from AyuVis demonstrated that compound AyuV-25 protected mice (12 weeks old) against lethal polymicrobial infection in cecal ligation and puncture (CLP) model alone, and in combination with standard antibiotic primaxin via intravenous (IV) dosing. In this presentation, we will discuss some of the preclinical results in animal model.
VMMC & Safdarjung Hospital, India
Mariya Saify is a Post-graduate student in Paediatrics in VMMC & Safdarjung Hospital New Delhi, India.
Background: Dengue is a major health concern in India. Marked increase in childhood dengue hemorrhagic fever (DHF) has stipulated the need for early predictive markers of severe dengue. To obviate the lacunae in literature, a study was designed to correlate symptoms at presentation and laboratory parameters with complications of DHF. The study also intended to determine association between deranged hematological profile and bleeding manifestation in these patients.
Methods: Children (1-12 years) with DHF were enrolled (2014-2015) for this study. Clinical presentation and biochemical parameters (platelet aggregation, platelet count, liver function test (LFT), activated partial thromboplastin time (APTT), prothrombin time (PT) plasma fibrinogen) were studied. Correlation of symptoms at presentation and deranged hematological profile with complications were analyzed.
Results: A significant association between bleeding and presence of rashes (p value 0.005), restlessness (p value-0.004), deranged APTT (p value 0.007) and decrease in plasma fibrinogen (p value-0.032) at presentation was prevailed. No relevant association between altered platelet aggregation and bleeding (p value-0.651) was inferred in our study. Headache (p value-0.011) and tourniquet test positivity (p value 0.023) were found to be associated significantly with shock. The study also deduced the correlation of bleeding (p value-0.003), restlessness (p value-0.047), decrease in plasma fibrinogen (p value 0.007) and platelet count (p value-0.005) with duration of stay and complications.
Conclusions: A child with rash, restlessness and headache at presentation identifies a high risk group in dengue patients. Patients with alteration of plasma fibrinogen, APTT and tourniquet test positivity should always be monitored for development of complication like shock and bleeding. Defect in platelet functions cannot be attributed as an independent risk for bleeding in DHF.
Sanjay Gandhi Postgraduate Institute of Medical Sciences, India
Kashi Nath Prasad has completed his MD from Institute of Medical Sciences, Banaras Hindu University, India. Currently, he is a Professor of Microbiology at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. He has guided 16 PhD and 10 MD students. He has published more than 210 scientific papers. He has received several awards by Academic Bodies and Scientific Societies. He is a Fellow of Royal Society of Tropical Medicine and Hygiene, International Congress of Environmental Research, National Academy of Medical Sciences (India) and Indian Academy of Tropical Parasitology. He has been invited as a speaker to more than 50 scientific events.
Multidrug-resistant (MDR) Gram-negative bacteria have emerged as the most dreaded health-care threat worldwide. Increased carbapenem resistance in Gram-negative bacteria has led to frequent use of colistin with risk of emergence of resistance. Recently several studies have reported plasmid (mcr-1 gene) mediated colistin resistance among Enterobacteriaceae isolated from veterinary and human sources. In the present study, we have investigated for the presence of mcr-1 gene in colistin resistant clinical isolates of Klebsiella pneumoniae, one of the most notorious bacteria in the family Enterobacteriaceae. Total 1000 Gram-negative bacteria isolated from clinical samples during January and February 2016 were subjected to antimicrobial susceptibility and 21 colistin resistant K. pneumoniae were detected. All 21 isolates were subjected to PCR for mcr-1 and blaNDM genes. Isolates positive for mcr-1 gene were further analyzed by Southern hybridization for localization of the gene either on plasmid or on chromosome. Clonal-relatedness of mcr-1 positive isolates was studied by pulsed field gel electrophoresis (PFGE). PCR based screening showed that 4 of 21 K. pneumoniae isolates harboured mcr-1 gene; one mcr-1 gene positive isolate also harboured blaNDM. All 3 mcr-1 gene positive isolates were clonally related by PFGE, while one blaNDM positive isolate was unrelated. Southern hybridization analysis showed that the mcr-1 gene was located on chromosome. In contrast to other earlier studies where the mcr-1 gene was plasmid borne, in the present study, it was localized on the chromosome. Further studies are required to know the genetic environment associated with mcr-1 gene to understand the source and its mechanism of transmission.
Centers for Disease Control and Prevention, USA
Katherine Bowden received her BS in Microbiology and PhD in Genetics from the University of Georgia. Over the past 4 years, she has led numerous projects under the scope of molecular diagnostics in the Pertussis and Diphtheria Lab at the Centers for Disease Control and Prevention. These projects include real-time PCR method validation, analysis of molecular epidemiology of pertussis epidemics, and development of a whole genome Multi Locus Sequence Typing (wgMLST) for pertussis. Additionally, she has coordinated numerous international trainings to build in-country capacity for both pertussis and diphtheria diagnostics in Latin American and Caribbean nations.
Statement of the Problem: Toxigenic strains of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis are capable of eliciting diphtheria toxin that causes symptoms of diphtheria, a vaccine-preventable disease. Historically, diagnosis of tox-bearing Corynebacterium species and verification of toxin production required an isolate. The purpose of this study was to validate a new triplex real-time PCR assay to both detect the tox gene and differentiate C. diphtheriae from the 2 other tox-bearing Corynebacterium species directly from clinical specimens.
Methodology & Theoretical Orientation: The triplex assays detect the Corynebacterium tox gene, C. diphtheriae rpoB, and the rpoB ortholog in C. ulcerans and C. pseudotuberculosis. A total of 101 archived clinical specimens (throat and nasal swabs) from suspected diphtheria cases, 20 Corynebacterium spp. and 15 other respiratory pathogen isolates were used to examine sensitivity and specificity of the triplex assay. Comprehensive in silico analysis of the oligo sequences was performed to confirm specificity. When available, results were compared to previous culture, CDC singleplex tox real-time PCR, and toxin production results. Positivity was determined with a Ct less than 40.
Findings: The triplex assay demonstrated an LOD of 10 genomic copies, 10X more sensitive than the current singleplex CDC assay. No cross-reactivity was found with 15 respiratory pathogens, including other Corynebacterium spp. Three specimens that tested negative with the current CDC assay were found to harbor the tox gene using the triplex assay, 2 of which were confirmed as C. diphtheriae.
Conclusion & Significance: The new triplex assay successfully differentiates C. diphtheriae from other toxigenic Corynebacterium species directly from clinical specimens and is more sensitive than the current CDC assay. Although a bacterial isolate is needed to confirm toxin production, when an isolate is not available, this assay can be used to identify a potentially toxigenic strain of Corynebacterium in clinical specimens. Further analysis will be conducted to determine if this assay is a good surrogate for identifying truly toxigenic strains.
College of Health Science, Ethiopia
Amanuel Lomencho has expertise in Internal Medicine and actively takes part in the care and treatment of HIV patients.
Despite current developments in HIV medicine and wide scale use of HAART, PCP (pneumocystis carinii pneumonia) still remains to be an important opportunistic infection especially in developing countries. Late diagnosis of HIV including first time diagnosis with an opportunistic disease is not uncommon in these settings. PCP usually presents acutely and is an important cause of AIDS related respiratory failure leading to ICU admission. A systematic review was done to look for predictors of mortality in HIV patients with severe PCP admitted to ICU. Studies that reported separate outcome for ICU patients with HIV/PCP were included. Pubmed, Embase and Medline search was made. Initial hit resulted 257 articles, out of which a final 8 were included in synthesis. Most studies were in the pre-HAART era. Results show that the use of mechanical ventilator, development of pneumothorax and duration of maximal therapy prior to ICU admission significantly predicted mortality in most studies. The results of this review could be of use to give emphasis to HIV patients who come with severe PCP ICU. More studies with bigger sample sizes and prospective in nature needs to be done to better explain the association.