Tu-Anh Huynh
Position title: Assistant Professor
Email: thuynh6@wisc.edu
Phone: 608-262-5960
Address:
Food Science
Bacterial signaling mechanisms, stress response, antibiotic resistance, pathogenesis
- Address
- Office: 127A Babcock, Lab: 231A Babcock
- Education
- Ph.D., University of California-Davis, Postdoc at the University of Washington
- Website
- https://huynhlab.labs.wisc.edu/
- Department
- Food Science
- Research Interests
- Bacterial signal transduction and pathogenesis, stress response, host-microbe interactions
- Research Fields
- Gene Expression, Genomics and Proteomics, Bacteria and Other Microbes
Research Description:
Bacteria are incredibly adaptable organisms that are intricately linked to human health and disease. The long-term goal of the Huynh lab’s research program is to develop therapeutic strategies that target bacterial adaptation mechanisms both in the environment and infected hosts. Towards that goal, we currently address four areas of investigation:
1. The role of small nucleotides in bacterial antibiotic resistance and pathogenesis: Nucleotide second messengers play essential role in bacterial sensing of antibiotic stress and infection conditions. In particular, we focus on c-di-AMP, an essential nucleotide in many bacterial pathogens such as Listeria monocytogenes, Staphylococcus aureus, Bacillus anthracis, and Mycobacterium tuberculosis. Both the depletion and accumulation of c-di-AMP sensitize bacteria to cell wall-targeting antibiotics and attenuate virulence. Therefore, disrupting c-di-AMP homeostasis is an attractive therapeutic strategy. We currently investigate how bacterial pathogens maintain c-di-AMP homeostasis under antibiotic stress and during infection, and define the molecular targets of c-di-AMP in these processes.
2. The pathogenesis of Listeria monocytogenes in the gastrointestinal tract: Listeria monocytogenes is a notorious foodborne pathogen with mortality rates of ~16%, one of the highest among foodborne infections. Although acquired orally, L. monocytogenes can rapidly cross the intestinal barrier to systemically infect multiple organs. While extensive research has elucidated how L. monocytogenes invades systemic organs, our knowledge of L. monocytogenes pathogenesis in the gastrointestinal tract remains extremely limited. Accumulating evidence indicates that L. monocytogenes attacks other gut bacteria, and the intestinal phase of infection is a determinant of infection outcome. We currently develop a GI tract infection model for L. monocytogenes and perform a genome-wide screen for genetic determinants of L. monocytogenes fitness in the GI tract.
3. Microbial interactions between bacterial pathogens with environmental microbiota: The vast majority of bacterial pathogens originate from natural environments, where they co-exist with the resident microbiota. Recent studies indicate that microbial diversity of an environment is a barrier to pathogen invasion. We currently investigate the reciprocal interactions between L. monocytogenes, as a model pathogen that is ubiquitously present in the environment, and the food and soil microbiota.
4. Discovery of antimicrobials and natural products: Combating antibiotic resistance requires continual discovery and development of new antibiotics, or adjuvants that increase the efficacy of current antibiotics. We exploit the vast microbial diversity of the food and soil microbiota to discover novel antimicrobials and natural products.
Representative Publications:
Siletti C, Freeman M, Tu Z, Stevenson DM, Amador-Noguez D, Sauer JD, Huynh TN (2024). C-di-AMP accumulation disrupts glutathione metabolism and virulence program expression in Listeria monocytogenes. Biorxiv.
Tu Z, Stevenson DM, McCaslin D, Amador-Noguez D, Huynh TN (2024). The role of Listeria monocytogenes PstA in β-lactam resistance requires the cytochrome bd oxidase activity. Journal of Bacteriology.
Gall AR, Hsueh BY, Siletti C, Waters CM, Huynh TN (2021). NrnA is a linear dinucleotide phosphodiesterase with limited function in cyclic dinucleotide metabolism in Listeria monocytogenes. Journal of Bacteriology.
Massa SM, Amar SD, Siletti C, Tu Z, Godfrey JJ, Gutheil WG, Huynh TN (2020). C-di-AMP accumulation impairs muropeptide synthesis in Listeria monocytogenes. Journal of Bacteriology.
Huynh TN, Choi PH, Sureka K, Ledvina HE, Campillo J, Tong L, Woodward JJ. (2016). Cyclic di-AMP targets the cystathionine beta-synthase domain of the osmolyte transporter OpuC. Molecular Microbiology.
Huynh, TN., Luo, S., Pensinger, D., Sauer, J.D., Tong, L., and Woodward, J.J. (2015). An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence. PNAS