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

Preventing tumor metastasis

Researchers at the Paul Scherrer Institute, together with colleagues from the pharmaceutical company F. Hoffmann-La Roche AG, have taken an important step towards the dev...

A new drug could revolutionize the treatment of ne…

The international team of scientists from Gero Discovery LLC, the Institute of Biomedical Research of Salamanca, and Nanosyn, Inc. has found a potential drug that may pre...

Interactions discovered in cells insulating nerve …

Schwann cells form a protective sheath around nerve fibres and ensure that nerve impulses are transmitted rapidly. If these cells are missing or damaged, severe neurologi...

Breast cancer can form 'sleeper cells' after drug …

Breast cancer medicines may force some cancer cells into 'sleeper mode', allowing them to potentially come back to life years after initial treatment. These are the early...

Anniversary of the pivotal RE-LY® trial marks a de…

Boehringer Ingelheim today announces the ten-year anniversary of the RE-LY® trial publication(1-3) recognising the contribution made in the decade since by patients, heal...

Experimental validation confirms the ability of ar…

Insilico Medicine, a global leader in artificial intelligence for drug discovery, announced the publication of a paper titled, "Deep learning enables rapid identification...

AstraZeneca agrees to buy US FDA Priority Review V…

AstraZeneca announced that it has agreed to buy a US Food and Drug Administration (FDA) Priority Review Voucher (PRV) for a total cash consideration of $95m from a subsid...

Boehringer Ingelheim eExpands KRAS cancer program …

Boehringer Ingelheim and Lupin Limited (Lupin) announced a licensing, development and commercialization agreement for Lupin's MEK inhibitor compound (LNP3794) as a potent...

Pfizer invests half billion dollars to advance sta…

Pfizer announced an additional half billion dollar investment for the construction of its state-of-the-art gene therapy manufacturing facility in Sanford, North Carolina...

The Pfizer Foundation invests in 20 organizations …

The Pfizer Foundation announced 20 grants* to help non-governmental organizations (NGOs), non-profits and social enterprises address critical health challenges related to...

FDA grants Fast Track designation for Farxiga in c…

AstraZeneca today announced that the US Food and Drug Administration (FDA) has granted Fast Track designation for the development of Farxiga (dapagliflozin) to delay the ...

Tagrisso approved in China as a 1st-line treatment…

AstraZeneca today announced that it has received marketing authorisation from China's National Medical Products Administration (NMPA) for Tagrisso (osimertinib) as a 1st-...