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Contact Dr. Schertzer at jschertz@binghamton.edu
Dr. Jeffrey W. Schertzer
I have always been interested in the mechanisms by which bacteria interact with each other and with the environments in which they live. Many of these interactions are mediated through structures at the bacterial cell surface, which serves as the interface between the cell and the environment. My training and research have focused on this area across multiple species and in different contexts. I received my PhD from the department of Biochemistry and Biomedical Sciences at McMaster University, where I worked under Dr. Eric Brown to characterize Gram-positive teichoic acid biosynthesis as a potential new target for antibiotic development. During my postdoctoral training with Dr. Marvin Whiteley in the department of Molecular Genetics and Microbiology at the University of Texas at Austin, I expanded my focus into cell-to-cell communication and cargo delivery in Gram-negative organisms. The focus of my own research laboratory centers around the biogenesis, packaging and targeting of outer-membrane-derived vesicles, which deliver countless important cargoes to both friends and foes under diverse environmental conditions. By understanding and exploiting these fundamental processes, we can develop interventions to control processes ranging from bacterial pathogenesis to biofilm formation.
Current Research
To carry out many functions, Gram-negative bacteria selectively package cargo into transport vesicles that bud off from their outer membrane. These structures are called Outer Membrane Vesicles (OMVs). Depending on their payload and target, OMVs can be involved in immune system avoidance/modulation, toxin delivery, interspecies competition, cell-cell communication, horizontal gene transfer and the development of biofilms. We are interested in understanding how Outer Membrane Vesicles (OMVs) are formed and how an organism directs what gets packaged within them. We also study the role of OMVs in community behaviors, such as cell-cell communication (quorum sensing) and biofilm formation. As an application of our research, we are exploring how natural and synthetic OMVs can be used to aid in vaccine development and antimicrobial drug delivery.
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Mechanisms of Outer Membrane Vesicle Biogenesis
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- PQS-induced membrane curvature induction in Pseudomonas aeruginosa
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Our group has demonstrated that the small signaling molecule PQS (Pseudomonas Quinolone Signal) interacts with the outer membrane and, through preferential interactions with asymmetrically distributed lipids, causes an uneven expansion of membrane leaflets that results in the induction of membrane curvature. This is the first step of OMV biogenesis. Current work is aimed at identifying the export mechanism that places PQS at the outer leaflet of the outer membrane, what chemical properties of membrane lipids mediate the PQS interaction and what environmental factors influence the susceptibility of the outer membrane to the action of PQS.
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- Detachment and release of OMVs from cells
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Induction of membrane curvature is not sufficient to fully explain the biogenesis of OMVs. In order to be released from cells as OMVs, the outer membrane must be severed from protein-peptidoglycan linkages that serve to maintain the integrity of the cell envelope. Our group has identified proteins that appear to mediate this detachment and we are actively studying the mechanisms of peptidoglycan release and the factors that regulate the novel and targeted reorganization of outer membrane-peptidoglycan linkages required for controlled release of OMVs.
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- Mechanisms of OMV biogenesis across species
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Induction of OMV biogenesis in response to small molecule inducers has been relatively well studied by our group using Pseudomonas aeruginosa as a model. Little is known, however, about the induction of OMV biogenesis in other species and we aim to uncover whether different small molecules (or similar factors) contribute to this process across Gram-negative genera. Our group has demonstrated that PQS is sufficient to induce OMV biogenesis in several species closely related to P. aeruginosa, but that susceptibility is influenced by the identity of the recipient strain. Further, we have identified active factors in the secreted repertoire of several Gram-negative species that reciprocally stimulate OMV biogenesis in P. aeruginosa. This cross-stimulation argues strongly that small molecule induced OMV biogenesis is a common feature across Gram-negative species, and further introduces the question of whether cohabitants of a single niche (including pathogens in an infection site) influence each other to produce more or different kinds of OMVs. Current research is aimed at characterizing the OMV-inducing molecules secreted by species other than P. aeruginosa and developing an understanding of the factors that explain observed differences in OMV-induction susceptibility between closely-related vs. distantly-related species. We are very interested in the implications these discoveries may have in the areas of bacterial ecology and virulence against humans.
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Bacterial Communities
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- OMV biogenesis and function in bacterial biofilms
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The biogenesis and function of OMVs have been studied almost exclusively under planktonic conditions. Our group has developed techniques to harvest and analyze OMVs from biofilms grown under many conditions and have confirmed that the production of biofilm OMVs is strongly dependent upon induction by PQS, as is true in planktonic cultures. However, our analysis was sensitive enough to also identify a small sub-population of distinct MVs that likely arose through cell lysis. We are actively investigating the differences between membrane vesicles produced by different mechanisms and at different times during biofilm development and we have identified differences in abundance and cargo of OMVs throughout the biofilm life-cycle that have motivated several new projects in the lab. So far, we have identified an important role for OMVs in the degradation of the extracellular matrix that allows for biofilm dispersion, but many important questions remain.
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- Pathogen synergy through cross-species induction of OMVs
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Our studies into the mechanism of OMV biogenesis across species led us to discover that factors secreted from several species were capable of inducing OMV biogenesis in separate recipient species when provided exogenously. This discovery has motivated us to expand our investigation into the behavior of multiple species when grown in co-culture. Techniques developed in our lab now allow us to quantify and analyze OMV produced in multispecies co-culture while also allowing us to identify which OMVs were produced by which interacting species. Exciting early results suggest that the OMVs produced by co-cultured pathogens are both more numerous and more cytotoxic to human cells. Continuing investigations in this project aim to help explain why multi-species infections show enhanced virulence over mono-species infections and generally lead to more severe disease.
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