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Full-Text Articles in Organisms

In Vivo Structures Of The Helicobacter Pylori Cag Type Iv Secretion System, Yi-Wei Chang, Carrie L. Shaffer, Lee A. Rettberg, Debnath Ghosal, Grant J. Jensen Apr 2018

In Vivo Structures Of The Helicobacter Pylori Cag Type Iv Secretion System, Yi-Wei Chang, Carrie L. Shaffer, Lee A. Rettberg, Debnath Ghosal, Grant J. Jensen

Veterinary Science Faculty Publications

The type IV secretion system (T4SS) is a versatile nanomachine that translocates diverse effector molecules between microbes and into eukaryotic cells. Here, using electron cryotomography, we reveal the molecular architecture of the Helicobacter pylori cag T4SS. Although most components are unique to H. pylori, the cag T4SS exhibits remarkable architectural similarity to other T4SSs. Our images revealed that, when H. pylori encounters host cells, the bacterium elaborates membranous tubes perforated by lateral ports. Sub-tomogram averaging of the cag T4SS machinery revealed periplasmic densities associated with the outer membrane, a central stalk, and peripheral wing-like densities. Additionally, we resolved pilus-like …


Genetic Signatures For Helicobacter Pylori Strains Of West African Origin, Kennady K. Bullock, Carrie L. Shaffer, Andrew W. Brooks, Ousman Secka, Mark H. Forsyth, Mark S. Mcclain, Timothy L. Cover Nov 2017

Genetic Signatures For Helicobacter Pylori Strains Of West African Origin, Kennady K. Bullock, Carrie L. Shaffer, Andrew W. Brooks, Ousman Secka, Mark H. Forsyth, Mark S. Mcclain, Timothy L. Cover

Veterinary Science Faculty Publications

Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of …


Peptidomimetic Small Molecules Disrupt Type Iv Secretion System Activity In Diverse Bacterial Pathogens, Carrie L. Shaffer, James A.D. Good, Santosh Kumar, K. Syam Krishnan, Jennifer A. Gaddy, John T. Loh, Joseph Chappell, Fredrik Almqvist, Timothy L. Cover, Maria Hadjifrangiskou Apr 2016

Peptidomimetic Small Molecules Disrupt Type Iv Secretion System Activity In Diverse Bacterial Pathogens, Carrie L. Shaffer, James A.D. Good, Santosh Kumar, K. Syam Krishnan, Jennifer A. Gaddy, John T. Loh, Joseph Chappell, Fredrik Almqvist, Timothy L. Cover, Maria Hadjifrangiskou

Pharmaceutical Sciences Faculty Publications

Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In …