Project Overview

Antimicrobial drug resistance in bacteria and parasites is a critical issue in developing countries. The incidence of drug resistance continues to climb. In particular, many Gram negative infections such as those caused by Salmonella and Shigella are resistant to virtually all relevant antibiotics. Very few new antibiotics have been developed over the past decades signifying problems with the antimicrobial approach. Furthermore, resistance to these new drugs arises rapidly as they are derivatives of existing medicines. In addition, there are several significant infectious diseases which lack an effective vaccine, despite extensive efforts to develop one. A novel approach is urgently needed to develop economical broad spectrum therapeutics to bacterial and parasitic infections.

To avoid the selection and spread of drug resistant variants of microbial pathogens, this project will develop an intervention strategy that targets and boosts innate immune responses to a number of infectious agents. We hypothesize that by not targeting the pathogen directly the selection of resistant variants can be avoided. We will focus on a variety of bacterial and parasitic pathogens, including enteric bacteria, Mycobacterium tuberculosis and Plasmodium falciparum.

Specific Objectives

• Establish a comprehensive database of host innate responses to major pathogens, including published literature, and data from human challenge studies and murine infection models
• Determine innate responses to a variety of known modulators and vaccine components
• Identify and characterize the mechanisms by which modulators of the innate response can be manipulated to control infection by testing in model systems
• Evaluate the role of modulators on human primary cells in an effort to translate the results from animal models to humans.
• Establish a critical path for developing innate modulators through pre-clinical evaluation prior to Phase I testing in humans

Grand Challenges in Global Health

The Grand Challenges in Global Health initiative was proposed by the Bill & Melinda Gates Foundation to address significant health issues in the developing world. This program brought together teams of the best scientists in the world to develop high impact scientific or technological innovations that would remove critical barriers to solving important health problems in the developing world. 

This project is funded through the Grand Challenges in Global Health (GCGH) initiative by the Foundation for National Institutes of Health (FNIH). Funding is also provided by the Canadian Institutes for Health Research (CIHR).

Contact Information

Project Leader: Brett Finlay, UBC