We study the molecular mechanisms used by bacteria to display and utilize virulence factors. Our goal is to leverage this knowledge to discover novel antibiotics and to develop new tools for biotechnological applications. Our research is interdisciplinary, but primarily employs NMR, crystallography, biochemical and microbiological methods.


Ongoing Research

Structural Biology of Protein and Polymer Display

Bacterial pathogens display virulence factors that enable them to adhere to host tissues, resist phagocytic killing, invade host cells and acquire essential nutrients. We are studying how bacteria synthesize and display two types of virulence factors: (i) pili, proteinaceous fibers that project from the bacterial cell surface to mediate adhesion, and (ii) Wall Teichoic Acids (WTAs), highly...

Molecular Basis of Heme-Iron Acquisition by Pathogenic Microbes

To successfully mount infections bacterial pathogens actively procure iron from their human host, which is extremely scarce because of nutritional immunity mechanisms. Hemoglobin within erythrocytes is an attractive source of iron, as it contains ~75-80% of the body’s total iron in the form of heme (iron-protoporphyrin IX). In ongoing research, we studying the molecular mechanisms used by Gram...

Chemical Biology: Antibiotic Discovery

The emergence of antibiotic resistance bacteria is significant health concern. Our goal is to discover new anti-infective agents that can be used to combat infections caused by methicillin resistant Staphylococcus aureus (MRSA) and other multidrug resistant Gram-positive bacteria. Toward this objective, we are using high throughput screening approaches to identify small molecules that...

Recent Publications

Kattke MD, Gosschalk JE, Martinez OE, Cascio D, Sawaya MR, Phillips M, Kumar G, Gale RT, Brown ED and Clubb RT.  Structure and mechanism of TagA, a novel membrane-associated glycosyltransferase that produces wall teichoic acids in pathogenic bacteria. PLoS Pathog. 15 2019; e1007723

Macdonald R, Mahoney BJ, Ellis-Guardiola K, Maresso M and Clubb RT. NMR Experiments Redefine the Hemoglobin Binding Properties of Bacterial NEAr-iron Transporter (NEAT) Domains. Protein Sci. 2019 (in press)

Siegel SD, Amer BR, Wu C, Sawaya MR, Gosschalk JE, Clubb RT and Ton-That H. A phosphotransferase LCP enzyme mediates glycosylation of a Gram-positive cell wall anchored protein. mBio. 10 2019; e01580-18

Macdonald R, Cascio D, Collazo MJ, Phillips M and Clubb RT. The Streptococcus pyogenes Shr protein captures human hemoglobin using two structurally unique binding domains. Journal of Biological Chemistry 293 2018; 18365-18377

McConnell SA, Amer BR, Muroski J, Fu J, Loo RO, Loo JA, Osipiuk J, Ton-That J and Clubb RT.  Protein labeling via a specific lysine-isopeptide bond using the pilin polymerizing sortase from Corynebacterium diphtheria. Journal of the American Chemical Society 2018; 140: 8420-8423

Chang C, Amer BR, Osipiuk J, McConnell SA, Huang I-H, Hsieh V, Fu J, Nguyen HH, Muroski J, Flores E, Loo RO, Loo JA, Putkey JA, Joachimiak A, Das A, Clubb RT and Ton-That H. In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin crosslinking.  Proceedings of the National Academy of Sciences (USA) 115 2018; E5477-E5486

Huang GL, Gosschalk JE, Kim YS and Clubb RT. Stabilizing displayed proteins on vegetative Bacillus subtilis cells. Appl Microbiol Biotechnol. 2018. doi:10.1007/s00253-018-9062-x

Sjodt M, Macdonald R, Marshall JD, et al. Energetics Underlying Hemin Extraction from Human Hemoglobin by Staphylococcus aureus. J Biol Chem. 2018. doi:10.1074/jbc.RA117.000803.

Jacobitz AW, Kattke MD, Wereszczynski J, Clubb RT. Sortase Transpeptidases: Structural Biology and Catalytic Mechanism. Adv Protein Chem Struct Biol. 2017;109. doi:10.1016/bs.apcsb.2017.04.008.

Chan AH, Yi SW, Weiner EM, et al. NMR structure-based optimization of Staphylococcus aureus sortase A pyridazinone inhibitors. Chem Biol Drug Des. 2017;90(3):327-344. doi:10.1111/cbdd.12962.