Phone
608-262-5960Office Location
Babcock Hall
1605 Linden Drive
Madison WI 53706
Lab: Room 231 Babcock
Office: Room 127A Babcock
Tu-Anh received her BS degree from the University of New South Wales (Australia), where she performed her thesis work on the microbial ecology of cocoa bean fermentation with Dr. Graham Fleet. She obtained her PhD degree from the University of California – Davis, where she trained with Dr. Valley Stewart on the NarXL/NarQP two-component signal transduction systems. She pursued her post-doctoral training with Dr. Josh Woodward at the University of Washington where she began to study the functions of c-di-AMP in bacteria.
Huynh TN and Stewart V (2023). Purine catabolism by enterobacteria. Advances in Microbial Physiology.
Gall AG, Hsueh BY, Siletta 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.
Jackson-Litteken CD, Ratliff CT, Kneubehl AR, Siletti C, Pack L, Lan R, Huynh TN, Lopez JE, Blevins JS. (2021). The diadenylate cyclase, CdaA, is critical for Borrelia turicatae virulence and physiology. Infection and Immunity.
Chow JTH, Gall AR, Johnson AK, Huynh TN (2021). Characterization of Listeria monocytogenes isolates from lactating dairy cows in a Wisconsin farm: antibiotic resistance, mammalian cell infection, and effects on the fecal microbiota. Journal of Dairy Science.
Massa SM, Sharma AD, Siletti C, Tu Z, Godfrey JJ, Gutheil WG, Huynh TN (2020). C-di-AMP accumulation impairs muropeptide synthesis in Listeria monocytogenes. Journal of Bacteriology.
Pham HT, Nguyen THN, Vu NTM, Huynh TN, Zhu Y, Huynh A, Chakrabortti A, Marcellin E, Lo R, Howard C, Bansal N, Woodward J, Liang ZX, Turner MS (2018). Enhanced potassium or glycine betaine uptake or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant. PLOS Genetics.
Rubin BE, Huynh TN, Welkie DG, Diamond S, Simkovsky R, Pierce EC, Taton A, Lowe LC, Lee JJ, Rifkin SA, Woodward JJ, Golden SS (2018). High-throughput interaction screens illuminate the role of c-di-AMP in cyanobacterial nighttime survival. Plos Genetics.
Townsley L, Yannarell SM, Huynh TN, Woodward JJ, Shank EA (2018). Cyclic di-AMP acts as an extracellular signal that impacts Bacillus subtilis biofilm formation and plant attachment. MBio.
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, and Woodward, JJ. (2015). Too much of a good thing: mechanisms for c-di-AMP depletion in the bacterial cytoplasm. Current Opinions in 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.
Huynh, TN, Lin, HY, Noriega, CE, Lin, AV, Stewart, V. (2015). Crosstalk inhibition nullified by a receiver domain missense mutation. Journal of Bacteriology.
Huynh, TN, Chen, LL, Stewart, V. (2015). Sensor-response regulator interactions in a cross-regulated signal transduction network. Microbiology.
Sureka, K, Choi, PH, Precit, M, Delince, M, Pensinger, DA, Huynh, TN, Jurado, AR, Goo, YA, Salidek, M, Iavarone, AT, Sauer, JD, Tong, L, Woodward, JJ. (2014). The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function. Cell
Huynh, TN, Noriega, CE, Stewart, V. (2013). Missense substitutions reflecting regulatory control of transmitter phosphatase activity in two-component signaling. Molecular Microbiology.
Seitzer, P., Huynh, TA, Facciotti, M. T. (2013). JContextExplorer: a tree-based approach to facilitate cross-species genomic context comparison. BMC Bioinformatics.
Huynh, TN, Stewart, V. (2011). Negative control in two-component signal transduction by transmitter phosphatase activity. Molecular Microbiology.
Huynh, TN, Noriega, CE, Stewart, V. (2010). Conserved mechanism for sensor phosphatase control of two-component signaling revealed in the nitrate sensor NarX. PNAS.
The role of c-di-AMP in bacterial adaptation and pathogenesis
In order to adapt, bacteria need to survey environmental conditions and reprogram themselves accordingly. There are many signaling mechanisms that enable bacteria to sense the environment, relay the signals, and regulate relevant molecular targets. Nucleotide second messengers are important components of all these events that ultimately facilitate bacterial growth and adaptation.
C-di-AMP is a ubiquitous nucleotide second messenger produced by thousands of bacterial species representing important human pathogens, gut symbionts, and environmental bacteria. C-di-AMP is essential to the growth of many bacteria, and its depletion results in loss of virulence, increased antibiotic susceptibility, among other defects. However, bacteria that produce c-di-AMP also need to maintain a balanced level of this nucleotide, since c-di-AMP accumulation also attenuates virulence and diminishes stress response.
A major focus of our lab is to understand how c-di-AMP mediates bacterial stress response, adaptation, and pathogenesis. Our models for c-di-AMP work are the human pathogen Listeria monocytogenes, the first bacterium found to make c-di-AMP; and the Gram-positive model Bacillus subtilis. Active projects address the following themes:
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How do bacteria regulate c-di-AMP levels to achieve homeostasis?
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How does c-di-AMP regulate its molecular targets?
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How does c-di-AMP regulate bacterial adaptation in mammalian hosts?
Mechanisms of antibiotic resistance
Antibiotic resistance is an urgent public health threat, with estimated 2.8 million antibiotic-resistant infections a year in the US. A long-term goal of our lab is to develop novel antibiotics or adjuvants that potentiate the efficacy of current antibiotics. We currently focus on understanding resistance mechanisms to cell wall-targeting antibiotics, including beta-lactams and D-cycloserine. Active projects address the following themes:
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How does c-di-AMP regulate bacterial cell wall synthesis and cell envelope stress response?
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What are the resistance mechanisms to cell wall-targeting antibiotics in Gram-positive bacteria?
Discovery of natural antimicrobials for food safety and infectious disease treatments
Combating antibiotic resistance requires continual discovery and development of new antibiotics, or adjuvants that increase the efficacies of current antibiotics. We employ both culture-based and culture-independent approaches to identify novel antimicrobials from diverse environmental and food fermentation microbiota. Active projects address the following themes:
- Develop biocontrol agents for foodborne pathogens, such as Listeria monocytogenes, from the food microbiota and food-grade microorganisms
- Discover novel antimicrobials from various microbiota for treatment of infectious diseases in humans and animals