Pathogen protection and virulence: Dark side of fungal membrane protein revealed

Blacksburg, Va. -- Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech and Montana State University have discovered a fungal protein that plays a key role in causing disease in plants and animals and which also shields the pathogen from oxidative stress. The researchers have found that the fungal protein TmpL is critical for the infection of host tissue and helps these pathogens regulate oxidative stress responses that are caused by the presence of destructive reactive oxygen species, a natural feature of the adaptive response to infection.

Dr. Chris Lawrence, Associate Professor at VBI and the Department of Biological Sciences at Virginia Tech and leader of the project, remarked: "The critical roles of reactive oxygen species in fungal development and virulence have been well established over the past half century. However little is known about how these molecules are produced or how the balance is achieved between their cell signaling roles on the one hand and their potentially destructive properties on the other. I believe we now have a unique opportunity to study a common fungal disease-associated mechanism in plants and animals that appears to be inextricably linked to the oxidative stress of the host-pathogen environment."

The scientists looked at two different fungal pathogens: Alternaria brassicicola, which causes widespread damage in crops like canola, cabbage and broccoli, and Aspergillus fumigatus, a human pathogen that often leads to fatal disease in immunocompromised patients. Infection with A. fumigatus can lead to invasive pulmonary aspergillosis, the leading cause of death due to invasive fungal infections in humans.

Said Lawrence: "This transdisciplinary project has involved bioinformatics, functional genomics, molecular biology, biochemistry, plant pathology, immunology, and medical mycology. We first discovered the gene encoding TmpL by computational screening and analysis of the A. brassicicola genome at VBI. Further investigation of the tmpL sequence and functional genomics analysis has allowed us to build up a picture of what the protein may look like in many filamentous fungi."

Dr. Biswarup Mukhopadhyay, an expert in microbial enzyme biochemistry at VBI, remarked: "The scientific evidence suggests that TmpL is a flavin-containing enzyme that possesses six membrane-spanning domains. Flavins are molecules that are involved in biological oxidation and reduction reactions. It seems likely that TmpL deploys electrons from NADPH, a key energy currency in the cell, via a flavin molecule to somehow modify subsequent signaling events that are linked to the overall oxidative state of the cell."