MRC National Institute for Medical Research, London
Science for Health
Maximiliano Gutierrez group project:
The M. tuberculosis perspective: understanding adaptation to the phagosome environment
Mycobacterial persistence is linked to two of the major obstacles against the eradication of tuberculosis: a large reservoir of people without clinical symptoms and complications in the treatment with the majority of antibiotics. In spite of its enormous relevance and clinical implications, the fundamental biology and a mechanistic understanding of mycobacterial persistence remains a puzzle for biologists
We are currently establishing a model of persistence that considers one of the most important aspects of mycobacterial lifestyle: intracellularity. In our group, we are developing, characterizing and validating this model as a new dynamic system to address questions in the field of mycobacterial persistence. For that, we combine live cell imaging and phenotypic analysis to provide insights into the mechanism of persistence. We also aim in the future to exploit this cellular system as a validated and predictive platform to find new effective chemical compounds against intracellularly persistent mycobacteria.
By using whole-genome sequencing and bioinformatics analysis, we are investigating the genetic modifications that are associated to intracellular persistent mycobacteria. We also analyze the phenotype that made these bacteria persist in host cells. The expression profile of the intracellular persisters will provide important and new components that are critical for mycobacterial persistence in a cell host context.
We undertake this question performing microarray gene expression of the mycobacterial persisters. The gene expression profile comparison with non-persistent mycobacteria will contribute to identify genes expressed during persistence. Combining this information with the genome sequence of the persistent mycobacteria, we will be able to provide an integrative analysis of the factors that make mycobacteria persist in host cells.
Our ultimate goal is to understand how the long-term manipulation of the phagosomal fate leads to mycobacterial persistence. Our findings will give important insights into the intracellular mechanism of mycobacterial persistence and evolution of the interaction between mycobacteria and host cells. Our goal is to translate these concepts to more complex (and still imperfect) animal models to develop new therapies against latent infection.
Selected publications
- Gutierrez MG, Mishra BB, Jordao ML, Elliott E, Anes E and Griffiths G. (2008)
NF-κB activation controls lysosome fusion-mediated killing of mycobacteria by macrophages
J Immunol 181(4), 2651-63 - Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI and Deretic V (2004)
Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.
Cell 119, 1-20
Gutierrez group
Recent publications
Research projects
- The host perspective: understanding phagosome biology and immune control of phagosome maturation
- The M. tuberculosis perspective: understanding adaptation to the phagosome environment
Gutierrez biography
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA
Top of page