The interactions of Shiga toxin producing Escherichia coli (STEC) and Shigella dysenteriae serotype 1 (SD1) with the intestinal
host environment were examined in a gnotobiotic piglet model using proteomic analysis techniques. Both pathogens cause
severe diarrhea in humans and occasionally serious systemic disease including hemolytic uremic syndrome which can be fatal.
The gnotobiotic piglet model is the most human-like non-primate model to study the pathogenesis of both pathogens. Proteomic
analyses for each of the bacteria isolated from the gut of infected animals revealed extensive proteomic adaptations. It was evident
that these adaptations were required for both Gram-negative bacterial species to survive in the enteric environment. Major
changes were the induction of anaerobic energy metabolism pathways, acid resistance systems, transport and metabolic systems
to increase bioavailability of lactose, phosphate, ammonia and NADPH and stress responses to detoxify reactive nitrogen species.
SD1 expressed a more diverse arsenal of type III secretion system effectors, apparently to boost the survival within epithelial
and/or phagocytic cells. Both pathogens modulated their cell surfaces, likely responding to the infiltration of innate and adaptive
immunity associated cells at the site of infection. Such changes included outer membrane proteins and biosynthetic machineries
for lipopolysaccharides. There was also evidence for the expression and secretion of antimicrobial proteins into the intestinal
lumen in response to colonization with STEC and SD1, such as the islet regenerating factor REG-3γ.
Rembert Pieper is an Associate Professor at the J. Craig Venter Institute in Rockville, Maryland. His laboratory conducts research in analytical
biochemistry with a technology emphasis on proteomics and a pathobiology emphasis on host-pathogen interactions and the discovery of disease
biomarkers. Dr. Pieper and his research group are currently involved in several projects integrating proteomics into multi-disciplinary system biology.
Investigations integrating sequencing-based microbiome analysis with metaproteomics are ongoing activities. He obtained his Ph.D. degree from
the Institute of Applied Chemistry, Technical University of Berlin, Germany (1989-1993). He conducted post-doctoral research in the Department
of Chemical Engineering, Stanford University (1994-1996), and the National Cancer Institute (1997-1998). He was a Staff Scientist and Director
for Protein Chemistry at Large Scale Biology Corporation (1999-2003), with an emphasis on protein biomarker discovery for non-communicable
diseases. He has co-authored 13 patent applications (8 issued patents) and 42 original research or review articles.
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals