Mycobacterium tuberculosis......can we beat it?

Mycobacterium tuberculosis is one of the most successful human pathogens. Treatment of tuberculosis requires a long duration time with the use of multiple drugs. There is also an alarming emergence of multidrug resistant M. tuberculosis. As a result a need have arisen to develop novel anti-tubercular agents. This EuroSciCon meeting will present cutting-edge research on developments in the detection and treatment of tuberculosis.

This event has CPD accreditation and will have a discussion panel session
+ show speakers and program
Mycobacterium tuberculosis in the Moonlight: The Unusual Preponderance of Moonlighting Proteins Used by Mycobacterium tuberculosis as Virulence Factors
Professor Brian Henderson, Eastman Dental Institute, London, UK
Protein moonlighting defines a recently recognised property of some proteins to have more than one unique biological function. Evidence is emerging that moonlighting proteins can play a role as bacterial virulence factors with a growing number of human pathogens. Most pathogens identified as having moonlighting proteins generally have only one, or at most two, such molecules. In contrast, at the time of writing, M. tuberculosis has 12 of its proteins functioning as moonlighting molecules each playing a potential, or identified, role in the virulence phenotype of this organism. Examples include the antigen 85 complex proteins which function both as mycosyltransferases and as ligands for the major host component fibronectin. Binding to fibronectin is a well-recognised method for bacteria both to adhere to the host and also to invade host cells. The cell stress protein, chaperonin 60.2 is found on the cell surface and functions as an adhesin and invasin by binding to the host cell receptor CD43 on macrophages. The paralogous protein, chaperonin 60.1, plays a major role in the generation of the multinucleate giant cells found in the tuberculoid granuloma, but appears not to be an adhesin. These chaperonins also have major effects on macrophage activation. The role of the various mycobacterial moonlighting proteins in tubercular disease will be described, and their potential as therapeutic targets will be explored

New approaches to sputum analysis; implications for treatment and transmission
Professor Mike Barer, Professor of Clinical Microbiology, University of Leicester, UK

Simple diagnosis of TB infection
Christopher Granger, Director, Global Professional Relations, Oxford Immunotec Ltd, Abingdon,United Kingdom
The T-SPOT.TB test identifies TB infection. Guidelines in many countries indicate its use in preference to the tuberculin skin test in many of the following patient groups:
• Contact tracing
• Healthcare workers
• HIV patients
• Immuno-suppressed patients, including pre-TNF screening
• New Entrants
• Hard-to- reach groups, including prisoners
The design of the test ensures it has excellent sensitivity and specificity. Additionally the simple phlebotomy and robust assay methodology allows the test to be carried out easily and simply in all these patient groups.

Mycobacterium tuberculosis – new ideas, new drugs and new vaccination strategies
Professor Graham Bothamley, Homerton University Hospital, London, UK
Effective short-course (6 month) treatment for tuberculosis has been available for almost 30 years. The failure to contain this problem is largely one of health care delivery. To short-circuit this problem, we need drugs which reduce the time required for effective treatment and vaccination strategies which prevent latent TB developing into infectious smear-positive disease. An understanding of latenttuberculosis is essential for both targets. M/XDR-TB offers an opportunity to test bactericidal drugs to replace isoniazid and drugs which act on slowly dividing populations of bacilli to replace rifampicin. Genomic and proteomic studies permit an examination of latency in Mycobacterium tuberculosis. New immunological tests offer the opportunity to examine markers of latency and reactivation.
15:30 – 16:00 Targeting the cell wall of Mycobacterium tuberculosis
Dr Luke Alderwick, Director of the Birmingham Drug Discovery and Screening Facility, University of Birmingham, UK
The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Recently, benzothiazinone (BTZ) inhibitors have shown nanomolar potency against both drug-susceptible and multidrug-resistant strains of the tubercle bacillus. However, their proposed mode of action is lacking structural evidence. This talk will cover some recent advances regarding the biosynthetic pathways leading to cell wall assembly including a report on the crystal structure of the BTZ target, a FAD-containing oxidoreductase M. tuberculosis DprE1, which is essential for viability. These results mark a significant step forward in the characterisation of a key TB drug target.

Talk title to be confirmed
Professor Edith Sim, Dean of the Faculty of Science Engineering and Computing at Kingston University, Kingston University, Surrey, UK

Biomarkers for monitoring TB treatment
Dr Timothy McHugh, Centre for Clinical Microbiology, UCL, UK



About the chair
Sanjib Bhakta’s continued research interest (currently funded by Medical Research Council, UK and Austrian Research Fund, EU) is focused on developing novel therapeutics to tackle persistence and drug resistance in Tuberculosis (XDR-TB, a global health emergency). He has published more than 25 original research articles in last 10 years for a number of internationally acclaimed journals including J. Exp. Med., JBC, Tuberculosis, Biochem. J., J. Antimicrob. Chemother., FEBS J. and Mol. Microbiology.
Following a BSc (Hons), an MSc and a PhD in Molecular Biology & Biochemistry from world class Universities & Research Institutions in India, Dr Bhakta joined the Oxford University Department of Pharmacology in 2001 as an ISIS innovation Senior Research Scholar and shortly after he was awarded with a Wellcome Trust International Travelling Fellowship. He graduated from The Queen’s College, University of Oxford in 2005 completing a second doctoral degree (DPhil) and received a “Sir William Paton Prize” for the best PhD presentation in Pharmacology. In 2006 he attained his first academic appointment at Birkbeck as a University Lecturer to lead his research and teaching. To date, he has supervised five PhD students, all of them completing their degree within four years, and he is supervising a number of UG/PG project students, three PhD students, two post-doctoral scientists and a UNESCO-L’Oreal International Fellow in his Laboratory. He became a Fellow of the Higher Education Academy, UK after achieving a post graduate certificate in Teaching and Life Long Learning in Higher Education (PGCHE) from the University of London in 2008.
He is a core member of Tuberculosis Drug Discovery-UK (http://www.tbd-uk.org.uk), the Institute of Structural and Molecular Biology, NIMR/Birkbeck/UCL and an affiliated academic Fellow of the Centre for Infection, Immunity and Disease mechanism, Brunel University. He is a member of a number of international societies and a review Editor for the Frontiers in Infectious Diseases. He was elected as a Fellow of the Royal Society of Medicine in 2008 and recognised as a Chartered Biologist in 2011.


About the speakers
Brian Henderson is Professor of Biochemistry at UCL's Eastman Dental Institute and is one of the early discoverers that bacteria secrete molecular chaperones which signal to host cells. This has led on to the thesis that bacteria use their molecular chaperones as secreted moonlighting proteins which aid in the process of bacterial virulence.

Graham Bothamley is a clinician experienced in the management of tuberculosis with a keen interest in translational research. He is Chair-elect of the Tuberculosis Network European Trialsgroup (TBNET, http://www.tb-net.org/). He is a member of the Stop TB Proposal Review Committee. He has published >75 papers in tuberculosis, recently addressing the clinical problems of M/XDRTB in Europe, the role of immunodiagnostic tests, TB control programs in the UK and the detection of latent TB in people living with HIV, a randomized controlled trial of vitamin D in TB and the potential diagnostic value of exhaled breath. He graduated from Pembroke College, University of Oxford in 1980 and gained a PhD in the immunology of TB from work undertaken at the MRC Tuberculosis and Related Infections Unit from 1985-88.

Edith Sim studied Biochemistry in Edinburgh University graduating in 1973. She then carried out her D. Phil. using the then new technique of 31PNMR of membrane phospholipids under the supervision of Charles Pasternak in the Biochemistry Department in Oxford. After 2 years as a Royal Society Exchange Fellow at the Centre d'Etudes Nucleaires in Grenoble studying hydrogen production in Pseudomonas aeruginosa she returned to Oxford, firstly as a Demonstrator in the Biochemistry Department working in collaboration with Bob Sim on immune system proteins of the complement system. A seminal paper on the study of the mechanism of activation of complement components C3 and C4 was the basis for a study on Hydralazine induced autoimmune disease, as a Wellcome Trust senior lecturer in the Pharmacology Department. The work in turn led to investigation of the pharmacogenetics of arylamine N-acetyltransferases (NATs) and development of understanding of these enzymes in animals and also in bacteria, identifying their mechanism of action. One NAT isoenzyme in humans (NAT1) is a breast cancer marker and she has developed specific ligands along with colleagues Steve Davies and Angie Russell which change colour on binding to human NAT1.She investigated NAT in mycobacteria and showed that the NAT protein along with other gene products of the same operon are good targets for anti-tubercular therapy. Research Interests: Currently working on a series of enzymes known as azoreductases.

Luke Alderwick is a Lecturer in Molecular Microbiology in the Institute of Microbiology and Infection (IMI) at the University of Birmingham. His many research interests revolve around understanding the biochemistry and molecular genetics of cell wall assembly in Mycobacterium tuberculosis. In close collaboration with Prof Gurdyal Besra and Dr Apoorva Bhatt, Dr Alderwick forms a trio of Principle Investigators heading one of the worlds leading academic research groups studying mycobacterial biochemistry, genetics and molecular microbiology. He is also the Director of the Birmingham Drug Discovery and Screening Facility (BDDSF), which is a new £700k high-throughput screening facility within the IMI designed specifically to allow academic-led translational drug discovery research, particularly in the area of discovering new anti-infectives.

Chris Granger has a graduate degree in pharmacology and a masters degree in business administration. He has spent the last 10 years developing the use and application of the T-SPOT.TB test throughout the world. He has been responsible for planning and running the clinical studies that were used to obtain regulatory approvals for the test and for providing data to many Guideline Development Groups.

21 Mar - 21 Mar 2013

London
United Kingdom
meeting website