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Mechanisms of drug action and drug resistance in mycobacteria

Objective

To investigate the influence of cell permeability and drug efflux systems on drug susceptibility
To identify the resistance mechanisms to streptomycin and clarithromycin
To study the mode of action of isoniazid
To characterise the cellular function of aminoglycoside acetyltransferase genes and their role in aminoglycoside inactivation
To search for a potential mdr gene in M.tuberculosis

Characterisation of drug resistance mechanisms at a genetic and biochemical level is a prerequisite for design and development of new drugs endowed with a high degree of selectivity that will prevent or curtail the spread of resistance conferring mutations. Implementation of new technology for rapid recognition of drug resistance will result in early initiation of effective chemotherapy as well as in preventing further transmission.
The project focuses at several aspects of mycobacterial drug resistance: acquired resistance to first-line drugs; mechanisms of the high inherent drug resistance; role and function of chromosomally encoded acetyltransferases; investigation of drug combination effects; multi-drug resistance genes. The project uses a multidisciplinary approach targeting resistance mechanisms at several levels, e. g. cell wall permeability, drug efflux, drug modifying enzymes and identification of intracellular targets of drugs. The project will allow the mechanisms of drug action and drug resistance to be elucidated both at the genetic and biochemical level.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Medizinische Hochschule Hannover
Address
1,Konstanty-gutschow-str. 8
30625 Hannover
Germany

Participants (5)

Imperial College of Science Technology and Medicine
United Kingdom
Address
Norfolk Place
W2 1PG London
Institut Pasteur
France
Address
28,Rue Du Docteur Roux, 28
75724 Paris
Swedish Institute for Infectious Disease Control
Sweden
Address
2,
105 21 Stockholm
Universidad de Zaragoza
Spain
Address
S/n,domingo Miral S/n
50009 Zaragoza
Università degli Studi di Pavia
Italy
Address
Via Abbiategrasso 207
27100 Pavia