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conferenceseries
.com
Volume 5, Issue 3 (Suppl)
J Infect Dis Ther, an open access journal
ISSN:2332-0877
Infectious Diseases 2017
August 21-23, 2017
3
rd
Annual Congress on
Infectious Diseases
August 21-23, 2017 San Francisco, USA
Dual targeting of the host-pathogen interface: Bacterial release and selective cytotoxicity
Valentin Trofimov, Nathalie Deboosere, Okryul Song, Joana Costa-Gouveia, Arnaud Machelart
and
Priscille Brodin
Center for Infection and Immunity of Lille, France
A
critical feature of the Mycobacterium tuberculosis bacillus is its ability to survive within macrophages, making these
host cells an ideal niche for persisting microbes. Identifying inhibitors of
M. tuberculosis
intracellular growth from large
chemical library has long been hampered by labor-cumbersome techniques. We thus developed a phenotypic cell-based assay
relying on automated confocal fluorescence microscopy and adapted it for the high throughput screen of compounds that
interfere with the multiplication of
M. tuberculosis
within macrophages. The current project is an early drug discovery that uses
alternative drug screening strategies and targets previously unexplored biological activities during tuberculosis (TB) infection.
The aim of the project is to establish a novel approach within the host pathogen interaction paradigm. The approach is based
on identification of the drugs and cellular pathways that trigger active bacterial release form its host into the extracellular
space or by specific killing of infected host cells. Both of these strategies can prevent the infection from spreading. Such
drugs and pathways might also facilitate the boosting of the immune response and enhance the effect of other conventional
antitubercular compounds. To reach our goal we established a high though put assay that uses a host-pathogen system based
on human cultivated macrophages and Mycobacterium tuberculosis H37Rv to test the activity of the drugs at the single cell
level. Screening will be followed by drug synergy studies with the use of known antitubercular compounds. Subsequently,
studying the drug mechanisms of action will be performed with cultivated macrophages.
Biography
Valentin Trofimov has his expertise in high-content and high-throughput drug screening. He aims to help eradication of the threat of tuberculosis worldwide.
Tuberculosis (TB) results in the death of millions of people every year. There is a growing threat because of the emergence of multidrug resistant strains. In order
to achieve that goal, new effective drugs and efficient TB therapies need to be discovered. He focuses his effort on early drug discovery with a close look at host-
pathogen interactions, since in vivo activities, such as intracellular host defense mechanisms, are largely overlooked in drug research.
valetin.trofimov@ibl.cnrs.frValentin Trofimov et al., J Infect Dis Ther 2017, 5:3 (Suppl)
DOI: 10.4172/2332-0877-C1-026