Assistant Professor
Research Interest: Harnessing microbes to understand and overcome gastrointestinal bacterial infections
Ph.D.: The University of Tennessee Health Science Center, Memphis, TN
Postdoctoral: Washington University School of Medicine, St. Louis, MO
Phone: 501-526-6809
Fax: 501-686-5359
Email: mwallace5@uams.edu
Currently accepting new students.
Research Description
The Wallace Lab is interested in exploring how we can harness bacteria and yeast to better understand and overcome antibiotic-resistant infections that occur within or arise from the gastrointestinal (GI) tract. We have two major research areas:
- Saccharomyces boulardii as a carrier for antimicrobial therapies. Protein-based therapies are a growing sector of the antimicrobial discovery pipeline including neutralizing antibodies, antimicrobial proteins, and anti-virulence factors. Delivering such therapies in stable form to the GI tract is challenging due to a rich population of proteases, digestive enzymes, and varying pH. Saccharomyces boulardii (Sb) is a probiotic yeast capable of producing effective protein-based therapies directly in the GI tract following oral administration. We are interested in developing Sb as a living carrier for protein-based therapies to treat Clostridioides difficile and enterotoxigenic Bacteroides fragilis in the GI tract following oral gavage. Both pathogens cause clinically significant diarrheal disease, and conventional antibiotic therapy can cause more harm than good due to disruption of the protective commensal microbiome. Therefore, a promising treatment strategy is delivery of alternative therapeutics directly targeting these pathogens in the GI tract using an engineered Sb chassis. We are additionally interested in synthetic biology-driven approaches to improve the performance of therapeutic secretion circuits in Sb.
- Understanding antimicrobial resistance in Bacteroides fragilis group bacteria. Bacteroides fragilis (BFG) bacteria represent some of the most well-characterized commensal bacterial species in our gut microbiome, yet are the most commonly isolated anaerobic bacteria from human infections. Antibiotic resistance trends are rising for BFG bacteria, and infections such as sepsis can have mortality rates as high as 50% in the absence of appropriate therapy. Key challenges in understanding antibiotic resistance in BFG bacteria include (1) the extensive phylogenetic diversity in BFG bacteria resulting in species-dependent trends in antibiotic resistance, and (2) the lack of characterization of antibiotic resistance mechanisms in these bacteria. We aim to identify functional antibiotic resistance genes using a functional genomics screen of nearly 200 clinical isolates of BFG bacteria, revealing species-dependent resistance mechanisms and potential new therapeutic strategies.
Join Us!
The Wallace Lab is new to UAMS and eager to consider applicants at all levels. For questions prior to application, please reach out to Dr. Wallace at MWallace5@uams.edu.
Key Publications
Complete bibliography on Google Scholar.
* Indicates equal contribution.
- Rebeck, ON*, Wallace, MJ*, Prusa, J*, Ning, J, Evbuomwan, EM, Rengarajan, S, Kwak, S, Zahrah, D, Tung, J, Liao, J, Mahmud, B, Mehta, R, Wang, B, Gorelik, MG, Helmink, BA, Dantas, G. “A yeast-based oral therapeutic delivers immune checkpoint inhibitors to reduce intestinal tumor burden.” Cell Chem Biol. 2025 Jan 16;32(1):98-110.e7
- Wallace, MJ*, Jean, S*, Wallace, MA, Burnham, CAD, Dantas, G. “Comparative genomics of Bacteroides fragilis group isolates reveals species-dependent resistance mechanisms and validates clinical tools for resistance prediction.” mBio. 2022 Jan 18;13(1):e0360321.
- Jean, S*, Wallace, MJ*, Dantas, G, Burnham, CAD. “Time for some group therapy: Update on identification, antimicrobial resistance, taxonomy, and clinical significance of the Bacteroides fragilis group.” J Clin Microbiol. 2022 Sep 21;60(9):e0236120.
- Dharuman, S, Wallace, MJ, Reeve, SM, Bulitta, JB, Lee, RE. “Synthesis and structure–activity relationship of thioacetamide-triazoles against Escherichia coli.” Molecules. 2022 Feb 24;27(5):1518.
- Wang, GC*, Wallace, MJ*, Krishnan, G, Olson, PD, Carlson, AL, Dantas, G, Fleckenstein, JM. “Spontaneous bacterial peritonitis caused by Bordetella hinzii.” Emerg. Infect. Dis. 2021 Aug 31; 27(11).
- Wallace, MJ*, Fishbein, SRS*, Dantas, G. “Antimicrobial resistance in enteric bacteria: current state and next-generation solutions.” Gut Microbes. 2020 Nov 9;12(1):1799654.
- Wallace, MJ, Dharuman, S, Fernando, DM, Reeve, S, Gee, C, Yao, J, Griffith, EC, Phelps, GA, Wright, WC, Elmore, JM, Chen, T, Lee, RE. “Discovery and characterization of the antimetabolite action of thioacetamide-linked 1,2,3-triazoles as disruptors of cysteine biosynthesis in gram-negative bacteria.” ACS Infect Dis. 2020 Mar 13;6(3):467-478.
- Griffith, EC*, Wallace, MJ*, Wu, Y, Kumar, G, Gajewski, S, Jackson, P, Phelps, GA, Zheng, Z, Rock, CO, Lee, RE, White, SW. “The structural and functional basis for recurring sulfa drug resistance mutations in Staphylococcus aureus dihydropteroate synthase.” Front Microbiol. 2018; 9:1369.