NIAID invests in basic research to understand the biology of microbes, their behavior, and how drug resistance develops. Understanding precisely how microbes cause disease (the process called pathogenesis) is also crucial for finding new ways to combat them.
NIAID conducts and supports basic research to understand the fundamental biology of disease-causing microbes and provides insight into the mechanisms they use to block antimicrobial drugs. This knowledge generates new ideas for ways to get around these mechanisms, by restoring the effectiveness of existing drugs or by identifying novel drug targets for the design of new antimicrobials.
Microbial pathogenesis is a key focus of basic research that studies how microbes cause disease, including how they colonize and invade the host, which toxins they produce, and how they avoid or overcome an attack by the host’s immune defenses. Basic research by NIAID scientists is revealing new details about microbial pathogenesis. For example, investigators have identified bacterial proteins produced by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) that destroy infection-fighting white blood cells. A better understanding of the role these proteins play in creating the conditions for severe CA-MRSA infections could lead to new ways to treat or prevent the illness.
NIAID supports research on host factors—specific traits that may influence an individual’s susceptibility or response to disease—and the pathogenesis of drug-resistant infections. For example, NIAID is advancing research on how to treat infectious diseases by targeting host pathways rather than the microbes themselves. An alternative to conventional antimicrobial drugs, host-targeted interventions could become a powerful new tool in the fight against drug resistance.
New pathways towards understanding drug resistance are revealed when scientists determine the sequence of genes that make up a microbe's genome. Genetic analysis can reveal vulnerable areas in a microbe's genome that could be potential drug targets. This information could also aid in developing better diagnostic tests. By isolating the same species of microbe from different geographic locations or from different human populations and comparing their genetic information, scientists may be able to identify when and where resistance first emerged in these species, as well as identify specific mechanisms of resistance.
Using genomic and additional "omic" information on proteins, sugars, and other compounds, the NIAID program in Systems Biology for Infectious Diseases Research investigates and identifies metabolic, regulatory, signaling, and other biological pathways generated by pathogen and host-pathogen interactions. The program's scientists use this information to build computer-based models that reveal clues about possible targets for new antimicrobial drugs. Virtual representations of potential drugs are first built by computer. Only the most promising of these virtual compounds are synthesized in the lab and tested for antimicrobial activity. This innovative method allows many compounds to be judged quickly for their potential utility.
AP Phyo et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet DOI: 10.1016/S0140-6736(12)60484-X (2012)
IH Cheeseman et al. A major genome region underlying artemisinin resistance in malaria. Science DOI: 10.1126/science.1215966 (2012)
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Last Updated January 07, 2013