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

New strategy to treat Parkinson's disease

Northwestern Medicine scientists have used patient-derived neurons to develop and test a new strategy to treat Parkinson's disease by mitigating the effects of harmful ge...

AI could offer warnings about serious side effects…

The more medications a patient takes, the greater the likelihood that interactions between those drugs could trigger negative side effects, including long-term organ dama...

OPKO and Pfizer announce positive Phase 3 top-line…

OPKO Health Inc. (NASDAQ: OPK) and Pfizer Inc. (NYSE: PFE) announced that the global Phase 3 trial evaluating somatrogon dosed once-weekly in pre-pubertal children with g...

Trastuzumab deruxtecan granted FDA Priority Review…

AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) today announced that the US Food and Drug Administration (FDA) has accepted for review the Biologics Lice...

The Bristol-Myers Squibb-Pfizer Alliance and Fitbi…

The Bristol-Myers Squibb-Pfizer Alliance and Fitbit announced at the TIME 100 Health Summit in New York that they are working together to help drive timely diagnosis of a...

Nplate® (romiplostim) now approved for earlier use…

Amgen (NASDAQ:AMGN) announced that the U.S. Food and Drug Administration (FDA) approved Amgen's Supplemental Biologics License Application (sBLA) for Nplate® (romiplostim...

Novartis announces that Jakavi® (ruxolitinib) meet…

Novartis today announced positive topline results from the Phase III REACH2 study evaluating Jakavi® (ruxolitinib) in patients with steroid-refractory acute graft-versus-...

Bayer launches LifeHub UK focused on artificial in…

Bayer launched LifeHub UK to accelerate and optimize disease detection and data-driven drug discovery by developing artificial-intelligence-enabled imaging solutions. The...

Amgen recommends rejection of 'mini-tender' offer …

Amgen (NASDAQ:AMGN) today announced that it has been notified of an unsolicited "mini-tender" offer dated Oct. 11, 2019, made by TRC Capital Corporation, a private Canadi...

First entirely digital clinical trial encourages p…

As little as a daily ping on your phone can boost physical activity, researchers from the Stanford University School of Medicine and their collaborators report in a new s...

Rare diseases: Over 300 million patients affected …

Rare diseases represent a global problem. Until now, the lack of data made it difficult to estimate their prevalence. Created and coordinated by Inserm, the Orphanet data...

Bed time is the best time to take blood pressure m…

People with high blood pressure who take all their anti-hypertensive medication in one go at bedtime have better controlled blood pressure and a significantly lower risk ...