Chemists characterize the fatal fungus among us

Life-threatening fungal infections affect more than two million people worldwide. Effective antifungal medications are very limited. Until now, one of the major challenges is that the fungal cell wall is poorly understood, which has impeded the development of effective antifungal medications that target the cell wall. However, an LSU chemist has identified for the first time the cell wall structure of one of the most prevalent and deadly fungi, which could usher in a new era of antifungal drug development to help save millions of lives.

LSU Department of Chemistry Assistant Professor Tuo Wang and colleagues have identified the high-resolution architecture of the cell wall of one of the most common fungi, Aspergillus fumigatus. Aspergillus fumigatus is airborne and can be found indoors and outdoors. In people with compromised immune systems, the fungi multiplies at an extraordinary rate. It affects more than 200,000 people annually including a quarter of all leukemia patients, and kills more than half of these patients.

"This is the first time anyone has looked at the whole cell of this fungi in its native state at such high resolution. Our work provides the molecular basis to engineer more effective antifungal drugs," Wang said.

His research was published this week in the journal Nature Communications. The LSU research team includes postdoctoral fellow Xue Kang, graduate students Alex Kirui and Malitha Dickwella Widanage, and undergraduate researcher Adrian Chen.

The scientists identified that Aspergillus fumigatus has a semi-waterproof core comprised of two types of stiff sugar molecules that is bridged by some highly branched sugars and coated by a layer of a sugar-protein mixture that constantly moves and undulates. The scientists pinpointed this structure by analyzing the fungi through dynamic nuclear polarization solid-state nuclear magnetic resonance spectroscopy at the National High Magnetic Field Laboratory in Tallahassee, FL. This method provides an unprecedented sensitivity and resolution to view the packing of molecules in native cells, without perturbation.

Next, Wang and colleagues will test the efficacy of various antifungal drugs against Aspergillus fumigatus in his lab at LSU. Also, they are characterizing other fungi in collaboration with Professor of Pediatrics and Microbiology Ping Wang in the Department of Microbiology, Immunology and Parasitology at the LSU Health Sciences Center in New Orleans.

"I want to share the structure and characterization of underinvestigated complex carbohydrates because they are large, complex and difficult to understand. We are also establishing a method for rapidly screening the drug effects of various fatal fungi and guiding the development of better medicines," said Wang at LSU.

Xue Kang, Alex Kirui, Artur Muszyński, Malitha C Dickwella Widanage, Adrian Chen, Parastoo Azadi, Ping Wang, Frederic Mentink-Vigier, Tuo Wang.
Molecular architecture of fungal cell walls revealed by solid-state NMR.
Nature Communicationsvolume 9, Article number: 2747 (2018). doi: 10.1038/s41467-018-05199-0.

Most Popular Now

Novo Nordisk announces plans to transform its appr…

Novo Nordisk announced plans to restructure its Research & Development (R&D) organisation to accelerate the expansion and diversification of its pipeline across serious c...

The Merck Accelerator Program 2019

The Merck Accelerator is looking for real partners so that you can work together in shaping the future. With programs in the headquarters in Germany, in China and the Sat...

World's largest Alzheimer's survey reveals most ad…

Amgen (NASDAQ:AMGN), Novartis and Banner Alzheimer's Institute (BAI), in association with Alzheimer's Disease International (ADI), announced results from the largest glob...

Imfinzi is the first immunotherapy to demonstrate …

AstraZeneca and MedImmune, its global biologics research and development arm, have presented data on overall survival (OS) in the Phase III PACIFIC trial of Imfinzi durin...

Pre-clinical success for a universal flu vaccine o…

Researchers from the University of Oxford's Department of Zoology have demonstrated pre-clinical success for a universal flu vaccine in a new paper published in Nature Co...

Discovery could explain failed clinical trials for…

Researchers at King's College London have discovered a vicious feedback loop underlying brain degeneration in Alzheimer's disease which may explain why so many drug trial...

Global survey reveals that physicians need more in…

Results from a new global survey revealed that more than one-third (36%) of the 310 physicians surveyed do not think they have sufficient information required to make inf...

Aspirin found not to prolong healthy aging

Taking a low-dose aspirin daily does not prolong healthy living in older adults, according to findings from the ASPirin in Reducing Events in the Elderly (ASPREE) trial p...

The Lancet Respiratory Medicine publishes first Ph…

AstraZeneca today announced publication of results from the KRONOS Phase III trial which evaluated the efficacy and safety of triple combination therapy PT010 (budesonide...

In clinical trials, new antibody therapy controls …

Thanks to improvements in antiretroviral therapy, HIV is now a manageable condition. Yet even the best drugs do not entirely eliminate the virus, which latently lingers i...

FDA approves first treatment for advanced form of …

The U.S. Food and Drug Administration today approved Libtayo (cemiplimab-rwlc) injection for intravenous use for the treatment of patients with metastatic cutaneous squam...

Clinical gene discovery program solves 30 medical …

A table in a recently published paper tells the story of 30 families who have, sometimes after years of searching, finally received an answer about the condition that has...