Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how a deadly microbe evades the human immune system and causes disease.
The study, published in the journal Proceedings of the National Academy of Sciences (PNAS), may help scientists develop new therapies or vaccines against infections caused by Cryptococcus neoformans. These fungal infections occur most commonly in those with compromised immune systems ©¤ especially AIDS patients and transplant patients who must take lifelong immunosuppressive therapy.
The fungus causes an estimated one million deaths each year worldwide, including some 600,000 in sub-Saharan Africa. The lead author of the study was Susana Frases-Carvajal, Ph.D., a postdoctoral fellow in microbiology & immunology at Einstein.
C. neoformans typically enters the body through the lungs and can spread throughout the body, including the brain. The resulting infection, called cryptococcosis, can cause chest pain, dry cough, abdominal swelling, headache, blurred vision, or confusion. The infection can be fatal, especially if not treated with antifungal medications.
"It's a horrendous disease, and even with therapy, you often can't get rid of it," says the paper's senior author, Arturo Casadevall, M.D., Ph.D., professor and chair of microbiology & immunology.
Scientists have known that the capsule surrounding C. neoformans is essential to its ability to cause disease. When the fungus enters a host, the capsule begins to enlarge. "As the capsule grows larger, it reaches a point where immune system scavenger cells, known as macrophages, can't swallow it," says Dr. Casadevall. "But we didn't understand the mechanism responsible for capsule growth."
The protective capsule of C. neoformans is composed of polysaccharides, which are long chains of sugar molecules, or saccharides. Using a technique called dynamic light scattering, Dr. Frases and her colleagues found that the capsule grows by linking more and more saccharides together at the outer edge of the capsule, forming giant molecules pointing in an outward, or axial, direction.
The findings point to potential new targets for drug intervention and reveal a new area of investigation into basic polysaccharide biology. Polysaccharides are poorly understood, partly because of the difficulty of working with them. "Also, scientists have tended to view polysaccharides as boring molecules that simply grow to a specified length," says Dr. Casadevall.
"But this study raises huge questions about polysaccharides," he adds. "For example, how does the organism assemble these molecules, and how does it know how to make molecules that are roughly the same length? We don't know. There appears to be a whole dimension of cellular machinery that we never knew existed."
The other co-authors of the paper, all of Universidade Federal do Rio de Janeiro, Brazil, are: Bruno Pontes, Leonardo Nimrichter, Marcio L. Rodrigues, and Nathan B. Viana.
The study, "Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules," appears in the January 27 issue of PNAS. http://www.pnas.org/content/106/4/1228.abstract
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island ¨C which includes Montefiore Medical Center, Einstein's officially designated University Hospital ¨C the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training.
Michael Heller | EurekAlert!
Further reports about: > Aids > C. neoformans > Cryptococcus neoformans > Einstein > PNAS > abdominal swelling > blurred vision > chest pain > confusion > deadly fungus > dry cough > fungal infections > headache > human immune system > immune system > immunosuppressive therapy > microbe > neoformans > polysaccharide
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
20.09.2017 | Life Sciences
20.09.2017 | Power and Electrical Engineering
20.09.2017 | Physics and Astronomy