Tag: Infectious Diseases

Flu Finds a Way In

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Influenza virus proteins in the act of self-replication. Credit: Wilson, Carragher and Potter labs, Scripps Research Institute.
Influenza virus proteins in the act of self-replication. Credit: Wilson, Carragher and Potter labs, Scripps Research Institute.

Flu viruses evolve rapidly, often staying one step ahead of efforts to vaccinate against infections or treat them with antiviral drugs. Work led by Jesse Bloom of the Fred Hutchinson Cancer Research Center has uncovered a surprising new flu mutation that allows influenza to infect cells in a novel way. Normally, a protein called hemagglutinin lets flu viruses attach to cells, and a protein called neuraminidase lets newly formed viruses escape from infected cells. Bloom’s lab has characterized a mutant flu virus where neuraminidase can enable the virus to attach to host cells even when hemagglutinin’s binding is blocked. Although the researchers generated the neuraminidase mutant studied in these experiments in their lab, the same mutation occurs naturally in strains from several recent flu outbreaks. There’s a possibility that flu viruses with such mutations may be able to escape antibodies that block the binding of hemagglutinin.

This work also was funded by NIH’s National Institute of Allergy and Infectious Diseases.

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Meet Galina Lepesheva

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Galina Lepesheva
Galina Lepesheva
Field: Biochemistry
Works at: Vanderbilt University, Nashville, TN
Born, raised and studied in: Belarus
To unwind, she: Reads, travels, spends time with her family

Galina Lepesheva knows that kissing bugs are anything but romantic. When the lights get low, these blood-sucking insects begin feasting—and defecating—on the faces of their sleeping victims. Their feces are often infected with a protozoan (a single-celled, eukaryotic parasite) called Trypanosoma cruzi that causes Chagas disease. Lepesheva has developed a compound that might be an effective treatment for Chagas. She has also tested the substance, called VNI, as a treatment for two related diseases—African sleeping sickness and leishmaniasis.

“This particular research is mainly driven by one notion: Why should people suffer from these terrible illnesses if there could be a relatively easy solution?” she says.

Lepesheva’s Findings

Currently, most cases of Chagas disease occur in rural parts of Mexico, Central America and South America. According to some estimates, up to 1 million people in the U.S. could have Chagas disease, and most of them don’t realize it. If left untreated, the infection is lifelong and can be deadly.

The initial, acute stage of the disease is usually mild and lasts 4 to 8 weeks. Then the disease goes dormant for a decade or two. In about one in three people, Chagas re-emerges in its life-threatening, chronic stage, which can affect the heart, digestive system or both. Once chronic Chagas disease develops, about 60 percent of people die from it within 2 years.

The Centers for Disease Control and Prevention (CDC) has targeted Chagas disease as one of five “neglected parasitic infections,” indicating that it warrants special public health action.

“Chagas disease does not attract much attention from pharmaceutical companies,” Lepesheva says. Right now, there are only two medicines to treat it. They are only available by special request from the CDC, aren’t always effective and can cause severe side effects.

Lepesheva’s research focuses on a particular enzyme, CYP51, that is the target of some anti-fungal medicines. If CYP51 can also act as an effective drug target for the parasites that cause Chagas, her work might help meet an important public health need.

CYP51 is found in all kingdoms of life. It helps produce molecules called sterols, which are essential for the development and viability of eukaryotic cells. Lepesheva and her colleagues are studying VNI and related compounds to examine whether they can block the activity of CYP51 in human pathogens such as protozoa, but do no harm to the enzyme in mammals. In other words, her goal is to cripple disease-causing organisms without creating side effects in infected humans or other mammals.

Lepesheva has tested the effectiveness of VNI on Chagas-infected mice. Remarkably, it has worked 100 percent of the time, curing both the acute and chronic stages of the disease. It acts by preventing the protozoan from establishing itself in the host’s body. If it is similarly effective in humans, VNI could become the first reliable treatment for Chagas disease.

Cool Image: Tiny Bacterial Motor

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Phillip Klebba, Kansas State University.

Credit: Phillip Klebba, Kansas State University.

It looks like a fluorescent pill, but this image of an E. coli cell actually shows a new potential target in the fight against infectious diseases. The green highlights a protein called TonB, which is produced by many gram-negative bacteria, including those that cause typhoid fever, meningitis and dysentery. TonB lets bacteria take up iron from the host’s body, which they need to survive. New research from Phillip Klebba of Kansas State University and his colleagues shows how TonB powers iron uptake. When TonB spins within the cell envelope (the bacteria’s “skin”) like a tiny motor, it produces energy that lets another protein pull iron into the cell. This knowledge may lead to the development of antibiotics that block the motion of TonB, potentially stopping an infection in its tracks.

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New Door Opens in the Effort to Stave off Mosquito-Borne Diseases

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Mosquito net Pyrethroids are used in mosquito nets distributed around the globe. Credit: Kurt Stepnitz, Michigan State University.

In the past decade, mosquitoes in many countries have become increasingly resistant to pyrethroid insecticides used to fend off mosquito-borne diseases such as malaria and dengue fever. Now, Ke Dong of Michigan State University and her colleagues have discovered a second pyrethroid-docking site in the molecular doorways, or channels, that control the flow of sodium into cells. Pyrethroids paralyze and kill mosquitoes and other insects by propping open the door and causing the pests to overdose on sodium, a critical regulator of nerve function. By providing new insights on pyrethroid action at the molecular level—and how mutations in the dual docking sites cause resistance—the findings open avenues to better monitoring and management of insecticide resistance.

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