Feldman Lab Research
Our lab is focused in microbial glycobiology and its exploitation for vaccine development. We also work on outer membrane vesicle (OMV) biogenesis. We are particularly interested in understanding virulence and survival mechanisms in the Gram-negative opportunistic pathogen Acinetobacter baumannii.
Acinetobacter baumannii pathogenesis
Hospital-acquired infections caused by opportunistic bacterial pathogens are a significant contributor to patient death and a major healthcare burden. Coupled with an alarming increase in antibiotic resistance, and few new antibiotics in development, drug-resistant bacterial pathogens have quickly established themselves as a global threat to healthcare security. A. baumannii has recently emerged as a one of the most concerning Gram-negative pathogens to infiltrate the hospital setting. New strategies for treating and managing multidrug-resistant A. baumannii infections are urgently needed, which requires a detailed understanding of this organism's pathobiology. We are investigating the cell surface components of A. baumannii, with an emphasis in the glycoconjugates, such as capsule and glycoproteins. We also study protein secretion in this organism. In particular, we focus on the type vi secretion system (T6SS), which presents the unique feature of being regulated by a multi-drug resistant plasmid that is easily lost by part of the bacterial population.
Biogenesis of Outer Membrane Vesicles
Biogenesis and trafficking of membrane vesicles are essential and well-studied processes in eukaryotes. In contrast, vesiculation in bacteria is not well understood. Outer membrane vesicles (OMVs) are produced in Gram-negative bacteria by blebbing of the outer membrane. OMV play roles in pathogenesis, cell-to-cell communication, immunomodulation, and stress response. However, many scientists are skeptical and believe that bacteria do not actively produce vesicles. We study OMV biogenesis in different microorganisms. We have shown that some bacterial species like Bacteroides fragilis and Porphyromonas gingivalis recruit specific protein cargo into OMV. Specifically B. fragilis packs hydrolases that can degrade proteins and polysaccharides and that may play a role in keeping the microbiota balance. Furthermore, we have identified enzymes involved in OMV formation in Salmonella.
Glycoengineering novel vaccines and therapeutics
Since the discovery that bacteria can N-glycosylate proteins and that their pathways can be functionally transferred into E. coli, bacteria have become an enormous resource for the development of novel glycoconjugate vaccines. Employing bacterial glycosylating enzymes, sugars and proteins could be "mixed" and "matched" to generate tailor-made glycoproteins. We demonstrated that several important bacterial pathogens additionally carry general O-glycosylation systems that target multiple proteins. We are currently developing several vaccines and therapeutics exploiting the bacterial glycosylation systems. Additionally we have engineered OMV displaying surface glycans and showed they constitute a versatile alternative platform for glycan-based vaccines.