Day 1 :
North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, India
Keynote: Study of musculoskeletal tuberculosis among patients in a tertiary care health setup in North East India
Time : 10:15-11:00
Anil Chandra Phukan has completed MD in Medical Microbiology from Dibrugarh University, Assam and DMV from Pune University, India and obtained DSA from COTTISA, Bangkok, Thailand under WHO Fellowship. He has worked as a Senior Scientist in Indian Council of Medical Research. Presently, he has been working as the Dean of Academics and Professor and Head of Microbiology Department, NEIGRIHMS, Shillong, India with active involvement in implementation of Revised National Tuberculosis Control Program, India and other national health programs. He has several national and international publications in reputed journals. His research activity focuses on understanding of molecular epidemiology of infectious diseases.
North East India is the north eastern region of the country comprising of eight states with 4500 km of international boundary with China, Myanmar, Bangladesh and Bhutan having >40 million population and 220 ethnic groups. North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong is the Post Graduate medical and health institute catering tertiary health care services to the patients of the entire region. North East India is bearing a considerable burden of tuberculosis with increasing cases of extra pulmonary tuberculosis where musculoskeletal tuberculosis is found to be a diagnostic dilemma to the treating clinicians. The study was carried out for understanding the prevalence of musculoskeletal tuberculosis and its clinic-bacterial profile among the patients attending the NEIGRIHMS hospital during 2015-2016 using both conventional and molecular diagnostic tools. Ultrasound guided pus aspiration, synovial fluid, bone biopsy and pus swabs from 52 suspected musculoskeletal tuberculosis patients were collected and subjected for laboratory detection of Mycobacterium tuberculosis infection employing morphological, cultural and molecular identifications. The study revealed 46.2% musculoskeletal tuberculosis with majority in the age group of 21-30 years (28.9%). Hip and knee joints were found to affected more (23.1% each) followed by lumber spines (19.2%). Ultra sound guided sample collection showed significantly better detection (71%) than the pus swabs. Molecular diagnosis using polymerase chain reaction assay is proved to be superior (46.2%) to culture (25%) and microscopy (1.92%) in terms of diagnostic accuracy, treatment initiation and avoidance of complications in better management of such paucibacillary tuberculosis.
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Germany
Keynote: Identification of inhibitors of the anti-infective target DXS using ligand-based virtual screening
Time : 11:15-12:00
Anna K H Hirsch has completed Natural Sciences at the University of Cambridge, spent one year at the Massachusetts Institute of Technology and did her Master’s project. She has received her PhD from the ETH Zurich under the supervision of Professor F Diederich. She has further joined the group of Professor Jean-Marie Lehn in Strasbourg as Postdoctorate and then took the position as an Assistant Professor at the University of Groningen. Later, she was promoted to Associate Professor. In 2017, she became Head of the Department for Drug Design and Optimization at the Helmholtz Institute for Pharmaceutical Research Saarland, Germany.
The enzymes of the methylerythritol phosphate (MEP) pathway are important drug targets given that pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum use this pathway for the biosynthesis of the essential isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), while humans exclusively utilize an alternative pathway. The thiamine-diphosphate-dependent enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS) catalyzes the first and rate-limiting step of the MEP pathway. To expand the structural diversity and obtain potent and selective inhibitors of DXS, we performed a ligand-based virtual screening (LBVS) campaign based on shape similarity to screen the ZINC database, starting from previously discovered DXS inhibitors as references. Biochemical evaluation of the top-scoring compounds against Mycobacterium tuberculosis DXS and further rounds of LBVS using the best hits as references afforded inhibitors in the single-digit micromolar range. In addition to the promising biochemical activity, the hits are active in cell-based assays against Plasmodium falciparum and even drug-resistant strains of Mycobacterium tuberculosis. Further, assays demonstrated their selectivity over mammalian thiamine-diphosphate-dependent enzymes, their lack of cytotoxicity and validated DXS as the intracellular target.