Progress 10/01/15 to 09/30/17
Outputs
Target Audience:Our target audience are peers and audiences interested in food safety. They are reached via meetings, presentations at Universities and in publications. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This work has supported in part three graduate students, Dr. Fang Yun Lim (graduated in 2016), and Ms. Mengyao Niu and Ms. Nanditha Ventatesh. They have and continue to recieve training in my laboratory, not just on scientific experimentation but also in ethics and presented this work in meetings and publications. How have the results been disseminated to communities of interest?We present our work through: 1. seminars at University of Wisconsin 2. Seminars at other universities 3. Presentations (oral and poster) and meetings 4. Publications 5. Interviews by newspapers, for example, please see the UW student newspaper article: https://badgerherald.com/news/2017/11/14/the-lab-report-keller-lab-works-to-regulate-cancer-causing-fungal-toxins-threatening-global-food-security/ What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
IMPACT: Fungi are ubiquitious microbes that can both benefit and harm society. Here we focus on the fungi that are harmful by growing on food and feed crops and secreting toxins in the edible portion of food and feed crops. Fungal toxins that are found in crops are called mycotoxins. There are three main classes (called genera) of mycotoxin producing fungi: Aspergillus, Penicillium and Fusarium. Our lab works with all three genera where we try to identify (1) genes/molecules/signals that are important for mycotoxin production by these fungi and (2) genes/molecules/signals that are important for growth and survival of these fungi. By finding such genes/molecules/signals, we can then create new strategies to combat these fungi to either prevent them from growing on food and feed crops or lessen their ability to produce mycotoxins on food and feed crops. This work is more important than ever as there are many scientific studies showing that climate change is likely to increase the levels of mycotoxins in our food and feed crops. Mycotoxins cause many illnesses in humans and animals. A good example is aflatoxin produced by Aspergillus flavus in crops such as peanuts, treenuts, corn and cotton seed. Aflatoxin is the most natural carcinogen known to humankind. Aflatoxin is a known cause of liver cancer and high amounts of this mycotoxin lead to death in humans and animals. Our research had four goals, all of which provide useful information on to how these fungi grow and/or produce mycotoxins: Goal 1) Determination if LaeB is also a regulator of mycotoxin synthesis in A. flavus. We have identified a new gene we call LaeB (loss of aflatoxin expression) that is required for aflatoxin production in A. flavus. This work is published in MBio in 2017 and includes as co-author HATCH supported PhD student Fang Yun Lim. Deletion of laeB results in an inability of the fungus to make aflatoxin. I currently have a supported PhD student and undergraduate student working on this project to try to figure out the mechanism by which LaeB regulates aflatoxin biosynthesis. 2) Determination if FleA is important in spore biology and adherence in Aspergillus spp. (and if time, Penicillium species). We have published on a lectin binding protein called FleA found in A. fumigatus and A. flavus) that allows fungal spores to bind to mucus in the lungs. We have now initiated studies to see if FleA is important for the mycotoxic species Penicillium expansum to bind to apples (P. expansum contaminates apples with the mycotoxin patulin). 3) Identification of quorum molecules, what the effect of such molecules are on Aspergillus growth and possible identification of receptors. Receptors are especially important for developing antifungals as they are often on the cell membrane surface of a fungus. This work was completed in 2012 and 2014 by a former PhD student, Dr. Affeldt. 4) This project will lead to an increase in the knowledge of what genes and proteins could be common targets in mycotoxigenic species for future control strategies. In addition to the first three goals, we are interested in any genes and proteins that could be useful targets to control mycotoxin producing fungi. In a brand new area of research in our lab, we have found that pathogenic fungi and bacteria can signal each other when growing close to each other. This signaling can increase mycotoxin production by the fungi. For example, we published in 2014 (J Chem Ecology 40:502-13) that volatiles of the phytopathogenic bacterium Ralstonia solanacearum can increase aflatoxin synthesis by Aspergillus flavus. This is of importance as both Ralstonia and Aspergillus are pathogens of peanuts. My new PhD student Nanditha (Thiruvannamalai) Ventatesh is now extending this work to see how this bacterium impacts mycotoxin production by the fungus Fusarium. We have just submitted a manuscript to ISME J on her new work.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Zhao X, Spraker JE, Bok JW, Velk T, He Z, Keller NP. (2017). A cellular fusion cascade regulated by LaeA is required for sclerotial development in Aspergillus flavus. Frontiers Microbiol. 8:1925.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Pfannenstiel BT, Zhao X, Wortman J, Wiemann P, Throckmorton K, Spraker JE, Soukup AA, Luo X, Lindner DL, Lim FY, Knox BP, Hass B, Fischer GJ, Choera T, Butchko RAE, Bok J-W, Affeldt KJ, Keller NP, Palmer JM (2017). Revitalization of a Forward Genetic Screen Identifies Three New Regulators of Fungal Secondary Metabolism in the Genus Aspergillus. MBio. 8(5). pii: e01246-17.
- Type:
Journal Articles
Status:
Submitted
Year Published:
2018
Citation:
Spraker JE, Wiemann P, Baccile J, Venkatesh N, Schumacher J, Schroeder FC, Sanchez LM, Keller NP (in revision). Conserved responses in a war of small molecules between fungi and a bacterium. ISME J.
- Type:
Other
Status:
Published
Year Published:
2017
Citation:
Wiemann P, Perevitsky A, Lim FY, Shadkchan Y, Knox BP, Landero Figueora JA, Choera T, Niu M, Steinberger A, W�thrich M, Idol RA, Klein B, Dinauer MC, Huttenlocher A, Osherov N, Keller NP. (2017). Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense. Cell Reports 9:1008-1021.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Rank LA, Walsh NM, Liu R, Lim FY, Bok JW, Huang M, Keller NP, Gellman SH, Hull CM. (2017). A cationic polymer that shows high antifungal activity against diverse human pathogens. Antimicrobial Agents Chemotherapy. 61(10). pii: e00204-17.
|
Progress 10/01/15 to 09/30/16
Outputs
Target Audience:The target audience is the general research community and participants at the Asilomar Fungal Genetics and American Phytopathological Society meetings. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Graduate Student Lim presented her work at international meetings, specifically at the 2016 Gordon conference on Cellular & Molecular Fungal Biology. Details: https://www.grc.org/programs.aspx?id=11335. Ms Lim graduated in August 2016 with a PhD. She mentored an undergraduate student who presented their work in lab meetings and a local University of Wisconsin undergraduate research symposium. How have the results been disseminated to communities of interest?Our work is largely disseminated by a publication and presentations at various meetings. What do you plan to do during the next reporting period to accomplish the goals?With a new graduate student to start in January 2017, we will continue with the work as outlined by the Hatch grant . We will: 1. Finish the work to see if FleA impacts the ability of Penicillium expansum to colonize apples; 2. Start studies of how LaeC works; 3. Finish the study of LaeA regulation of BrlA in at least one Aspergillus species
Impacts
What was accomplished under these goals?
Our focus was on identifying regulators of mycotoxin biosynthesis or regulation of growth of the fungi that make mycotoxins. Mycotoxins are a major type of plant disease and result in the most yield loss of any plant disease type. The mycotoxin producing fungi cause yield loss through tissue destruction and present a tremendous health problem by the production of mycotoxins in seed. Our goals for this present Hatch are: (1) identification of regulators of mycotoxin production in Aspergillus spp and/or (2) continue progress in identifying molecules in Aspergillus to complete its disease cycle. Regarding goal 1, we have identified several global regulators of mycotoxin production. For example, a recent finding, not yet published, are two new genes called LaeB and LaeC that regulate sterigmatocystin production in A. nidulans and aflatoxin production in A. flavus. We have recently disrupted these genes in A. flavus and A. fumigatus and have started work on the LaeC project (with a non-Hatch supported graduate student) and LaeB (with non-Hatch supported senior scientist). Previously, we found that LaeA (already published as regulating all known mycotoxins including not only Aspergillus mycotoxins but also Fusarium and Penicillium mycotoxins) regulates production of spore toxins through the transcription factor known as BrlA. BrlA was identified several years ago as a protein necessary for Aspergillus species to produce conidiophores and, hence, conidia the initial inoculum. The brlA gene is positively regulated by LaeA in all Aspergillus species we have looked at (e.g. A. flavus, A. nidulans and A. fumigatus) and we have recently found that LaeA regulates brlA expression via chromatin remodeling of the brlA promoter. PhD student Fang Yun Lim has identified several spore specific toxins regulated by LaeA in A. fumigatus, which have an impact on the human immune system. She has published on some of these (in past years). Ms. Lim is asking if BrlA regulation of spore metabolites are important for fungal survival. Regarding goal 2, Ms Lim has made progress on defining a new toxin cluster that appears important for copper homeostasis in A. fumigatus. A second project Ms. Lim was involved in concerns a lectin binding protein called FleA found in A. fumigatus and A. flavus. This latter work was published this year. We have initiated studies to see if FleA is important for the mycotoxic species Penicillium expansum to bind to apples (P. expansum contaminates apples with the mycotoxin patulin).
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Kerr SC, Fischer GJ, Sinha M, McCabe O, Palmer JM, Choera T, Lim FY, Wimmerova M, Carrington SD, Yuan S, Lowell CA, Oscarson S, Keller NP and Fahy JV (2016) FleA expression in Aspergillus fumigatus is recognized by fucoslated structures on mucins and macrophages to prevent lung infection. PloS Pathogens. 12(4):e1005555.
|