Current Members

The Pel polysaccharide is a widespread biofilm component involved in chronic infections. It is produced by Gram-negative and Gram-positive bacteria and typically regulated by the second messenger c-di-GMP. Interestingly, Gram-positives contain a subset of species that lack genes required for the c-di-GMP pathway. My project aims to understand the underlying principles of Pel regulation and production in this subset using S. intermedius as model organism with the hope of finding an alternative treatment approach for Pel related infections.

Development of glycoside hydrolases as therapeutics.

Galactosaminogalactan (GAG) is a major biofilm polysaccharide in Aspergillus spp. GAG production is an important virulence factor contributing to millions of invasive aspergillus infections in immunocompromised individuals each year. My project focuses on using a structural approach to understand the mechanism of synthesis and export of the GAG polysaccharide by the large, multi-domain transmembrane glycosyltransferase Gtb3.

The Pel polysaccharide is a major component of the Pseudomonas aeruginosa biofilm produced by the pelABCDEFG operon, which contributes to its multi-antibiotic resistance. Previous studies have shown that PelA deacetylase activity is crucial for detection of Pel polymer produced by P. aeruginosa, and this activity is enhanced in the presence of the scaffolding protein PelB. My project aims to understand the mechanism of Pel processing and export by the PelAB complex. Using structural biology techniques such as cryo-EM and X-ray crystallography, I will focus on investigating structural changes induced in PelA upon complex formation with PelB, which can give insights on how PelB regulates PelA activity. Understanding the Pel biosynthetic complex mechanistically will allow us to develop targeted therapeutics against P. aeruginosa infections.

The cyclic dynamics of extension, surface adherence, and retraction of the Type IV pili (T4P) are powered largely by cytoplasmic motor ATPases via ATP hydrolysis. Previous studies in the T4aP system demonstrated the existence of multiple ATPases performing exclusive roles in either extension or retraction. Conversely, recent evidence in the Tad (tight adherence) system suggests that a bifunctional ATPase can drive both functions. Hence, my current project utilizes an X-ray crystallographic approach to determine the structure of the Tad pilus ATPase, leveraging C. crescentus as a model. The results will help us understand how structural differences amongst these ATPases ultimately produce varying functions.