Tu-Anh Huynh, PhD

The Huynh lab studies mechanisms of bacterial adaptation, pathogenesis, and antibiotic resistance, with the long-term goal to develop novel antibacterial treatments. Current research in our lab is currently exploring three themes:

1 – Cyclic dinucleotide signaling in bacterial stress response and pathogenesis: 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 aim to understand how bacteria regulate c-di-AMP levels to achieve homeostasis, how c-di-AMP regulates its molecular targets in bacterial cells, and how c-di-AMP regulates pathogen adaptation in mammalian hosts.

2- Mechanisms of antibiotic resistance: Antibiotic resistance is a prominent 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 aim to understand the mechanisms of beta-lactam tolerance by Listeria monocytogenes, the mechanisms by which c-di-AMP regulates resistance to cell wall-targeting antibiotics, and the resistance mechanisms to D-cycloserine in Gram-positive bacteria.

3- Discovery of natural antimicrobials: 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 aim to develop biocontrol agents and discover novel antimicrobials from food and environmental microbiota for treatment of infectious diseases in humans and animals.

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; doi: 10.1128/JB.00206-21. Epub 2021 Oct 18 

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, IAI.00787-20. doi: 10.1128/IAI.00787-20. PMID: 33846120

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. doi: 10.3168/jds.2020-18885. PMID: 33516554 

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, JB.00307-20; DOI: 10.1128/JB.00307-20.

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 102: 233-243 (PMID: 27378384). doi: 10.1111/mmi.13456.

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 30: 22-29 (PMID: 26773214). doi: 10.1016/j.mib.2015.12.007.

 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. Proceedings of the National Academy of Sciences USA 112: E747-756 (PMID: 25583510). PMCID: PMC4343097. doi: 10.1073/pnas.1416485112.

 Huynh, TN, Lin, HY, Noriega, CE, Lin, AV, Stewart, V. (2015). Crosstalk inhibition nullified by a receiver domain missense mutation. Journal of Bacteriology 197: 3294-306 (PMID: 26260457). PMCID: PMC4573717. doi: 10.1128/JB.00436-15.

 Huynh, TN, Chen, LL, Stewart, V. (2015). Sensor-response regulator interactions in a cross-regulated signal transduction network. Microbiology 161, 1504-15 (PMID: 25873583). doi: 10.1099/mic.0.000092. 

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 158, 1389-1401 (PMID: 25215944). PMCID: PMC4166403. doi: 10.1016/j.cell.2014.07.046.

 Huynh, TN, Noriega, CE, Stewart, V. (2013). Missense substitutions reflecting regulatory control of transmitter phosphatase activity in two-component signaling. Molecular Microbiology 88, 459-472 (PMID: 23517441). PMCID: PMC3633741. doi: 10.1111/mmi.12195.

 Huynh, TN, Stewart, V. (2011). Negative control in two-component signal transduction by transmitter phosphatase activity. Molecular Microbiology 82, 275-286 (PMID: 21895797). PMCID: PMC3192241. doi: 10.1111/j.1365-2958.2011.07829.x.