Harvard Medical School
Suzanne Walker  

Dept. of Microbiology and Immunobiology

Harvard Medical School

HIM, Room 1013

4 Blackfan Circle

Boston, MA 02115

phone: 617-432-5488

fax: 617-738-7664


Research Summary

The Walker Lab works in two major areas.

We are working to develop a comprehensive understanding of the bacterial cell envelope – how it is assembled, how it changes in response to stress, and what its key vulnerabilities are – and to exploit this understanding to identify small molecules that inhibit cell envelope targets. Our goal is to contribute new knowledge, innovative methods, and compounds for use to combat antibiotic resistance. Pathogens of primary interest include MRSA and Streptococcus pneumoniae.

We are also working to elucidate the chemistry of O-GlcNAc transferase (OGT) and to develop genetic methods and small molecules to manipulate OGT in mammalian cells. Our goal is to use separation-of-function mutants and selective inhibitors to deconvolute OGT’s complex biology and assess its potential as a therapeutic target.

Approaches: Biochemistry (pathway reconstitution, target characterization, compound mechanism of action), genetics (evaluation of cellular function), high throughput screening (inhibitor discovery), systems biology (genome-wide perturbation analysis of antimicrobial compounds; other –omics approaches applied to small molecules).

Selected Publications

Vickery CR, Wood BM, Morris HG, Losick R, Walker S. Reconstitution of Staphylococcus aureus Lipoteichoic Acid Synthase Activity Identifies Congo Red as a Selective Inhibitor. J. Am. Chem. Soc. 2018; doi: 10.1021/jacs.7b11704.

Welsh MA, Taguchi A, Schaefer K, Van Tyne D, Lebreton F, Gilmore MS, Kahne D, Walker S. Identification of a Functionally Unique Family of Penicillin-Binding Proteins. J. Am. Chem. Soc. 2017; 139:17727-30.

Matano LM, Morris HG, Hesser AR, Martin SES, Lee W, Owens TW, Laney E, Nakaminami H, Hooper D, Meredith TC, Walker S*. Antibiotic That Inhibits the ATPase Activity of an ATP-Binding Cassette Transporter by Binding to a Remote Extracellular Site. J. Am. Chem. Soc. 2017; 139:10597-600.

Srisuknimit V, Qiao Y, Schaefer K, Kahne D, Walker S*. Peptidoglycan Cross-Linking Preferences of Staphylococcus aureus Penicillin-Binding Proteins Have Implications for Treating MRSA Infections. J. Am. Chem. Soc. 2017; 139:9791-4.

Qiao Y, Srisuknimit V, Rubino F, Schaefer K, Ruiz N, Walker S, Kahne D. Lipid II overproduction allows direct assay of transpeptidase inhibition by beta-lactams. Nat. Chem. Biol. 2017; 13:793-8.

Schaefer K, Matano LM, Qiao Y, Kahne D, Walker S*. In vitro reconstitution demonstrates the cell wall ligase activity of LCP proteins. Nat. Chem. Biol. 2017; 13:396-401.

Lee W, Schaefer K, Qiao Y, Srisuknimit V, Steinmetz H, Müller R, Kahne D*, Walker S*. The mechanism of action of lysobactin. J. Am. Chem. Soc. 2016; 138:100-3.

Pasquina L, Santa Maria JP Jr, Wood BM, Moussa SH, Matano L, Santiago M, Martin SES, Lee W, Meredith TC, Walker S*. A synthetic lethal approach for compound and target identification in Staphylococcus aureus. Nat. Chem. Biol. 2016; 12:40-5.

Santiago M, Matano LM, Moussa SH, Gilmore MS, Walker S*, Meredith TC*. A new platform for ultra-high density Staphylococcus aureus transposon libraries. BMC Genomics 2015; 16:252.

Qiao Y, Lebar MD, Schirner K, Schaefer K, Tsukamoto H, Kahne D*, Walker S*. Detection of Lipid-Linked Peptidoglycan Precursors by Exploiting an Unexpected Transpeptidase Reaction. J. Am. Chem. Soc. 2014; 136:14678-81.

Brown S, Xia G, Luhachack LG, Campbell J, Meredith TC, Chen C, Winstel V, Gekeler C, Irazoqui JE, Peschel A, Walker S*. Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids. Proc. Natl. Acad. Sci. USA 2012; 109:18909-14.

Swoboda JG, Meredith TC, Campbell J, Brown S, Suzuki T, Bollenbach T, Malhowski AJ, Kishony R, Gilmore MS, Walker S*. Discovery of a small molecule that blocks wall teichoic acid biosynthesis in Staphylococcus aureus. ACS Chem. Biol. 2009; 4:875-83.

(*Corresponding Author)