Infectious disease

By identifying new compounds that selectively block mitochondrial respiration in pathogenic fungi, Whitehead Institute scientists have identified a potential antifungal mechanism that could enable combination therapy with fluconazole, one of today’s most commonly prescribed fungal infection treatments. Severe, invasive fungal infections have a mortality rate of 30-50% and cause an estimated 1.5 million deaths worldwide annually. Current antifungal therapies are hampered by the increasingly frequent emergence of drug resistance and negative interactions that often preclude combination use.

The germinal centers that form in the body’s lymph nodes work as a fitness boot camp in which B cells evolve to produce antibodies of increasingly higher affinity to an invading pathogen. This new finding from Whitehead Institute scientists overturns a previously held notion that only a narrow range of B cells can survive this training and go on to secrete high-affinity antibodies. This revised understanding may aid development of effective vaccines against HIV, influenza, and other viruses that mutate rapidly.

The most common fungal pathogen in humans, Candida albicans, rarely develops resistance to the antifungal drug amphotericin B (AmB).  This has been puzzling as the drug has been in clinical use for over 50 years. Whitehead Institute scientists have now discovered why.  The genetic mutations that enable certain strains of C. albicans to resist AmB simultaneously render it highly susceptible to environmental stressors and disarm its virulence factors.

Revealing influenza’s truly insidious nature, Whitehead Institute scientists have discovered that the virus is able to infect its host by first killing off the cells of the immune system that are actually best equipped to neutralize the virus.

By directly altering the gene coding for the prion protein (PrP), Whitehead Institute researchers have created mouse models of two neurodegenerative prion diseases, each of which manifests in different regions of the brain.  These new models for fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) accurately reflect the distinct patterns of destruction caused by the these diseases in humans.  Remarkably, as different as each disease is, they both spontaneously generate infectious prions.

By tracking the previously unknown movements of a set of specialized cells, Whitehead Institute scientists are shedding new light on how the immune system mounts a successful defense against hostile, ever-changing invaders.

In an approach with the potential to aid therapeutic vaccine development, Whitehead Institute scientists have shown that enzymatically modified antibodies can be used to generate highly targeted, potent responses from cells of the immune system.

Using an unusual human cell line of this type, Whitehead Institute researchers and their collaborators performed a genetic screen and identified a protein used by Ebola virus to gain entry into cells and begin replicating. The discovery may offer a new approach for the development of antiviral therapeutics.