Microbes that cause many of the world's most serious infectious diseases, such as HIV, hepatitis B, and tuberculosis, increasingly are becoming resistant to antibiotics and other medications. Meanwhile, there are few effective vaccines to prevent these infections. One new approach with potential both to lessen the spread of drug resistance and to treat disease proposes developing drugs that target components of human cells essential to the replication of microbes, rather than the microbes themselves. This may make it much more difficult for microbes to develop resistance to the drugs.
 
Dr. Jiang’s team is identifying components of human cells that microbes use to establish an infection and replicate but that are not essential to the human host. Better understanding of microbial replication and survival from the view of host cells, the project team anticipates, will provide a foundation for novel therapeutic approaches to combat infectious diseases while simultaneously providing a low likelihood of inducing drug resistance. These compounds could potentially work by interrupting microbes from creating the environment they need to replicate in human cells.

Focusing on potential treatments for HIV, tuberculosis, and hepatitis B, Dr. Jiang’s project aims to screen chemical libraries for inhibitors of validated host targets that can be further developed and evaluated as drugs. Since the drugs would not be targeted at the pathogen, investigators expect that microbial variants resistant to the drug will not be selected.
 
The project team is using several approaches to identify host targets, including:

• Differential gene expression of infected and uninfected cells.
• RNAi to silence suspected targets.
• Effect of inhibitors of known or suspected targets on pathogen replication.