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Alzheimer, M.

Publications and source records attributed to Alzheimer, M..

2 recordsLinked to original sources

Functional genomics of Campylobacter-host interactions in an intestinal tissue model reveals a small lipoprotein essential for flagellar assembly

Campylobacter jejuni is the leading cause of bacterial food-poisoning, with motility being an essential virulence factor. While many aspects of flagella biogenesis have been studied, a complete picture of the components and regulators of these multi-protein machines is still missing. To identify genes crucial for C. jejuni pathogenesis and motility, we applied transposon sequencing in a humanized tissue model. This revealed three largely uncharacterized genes (pflC , pflD , pflE ) as essential for motility. While PflC/D turned out to be components of the flagellar motor disk structures, PflE is a small protein of only 57 aa. PflE strikingly affects motor biogenesis, with complete loss of motor structures upon its deletion. We demonstrate PflE is a lipoprotein and supports outer-membrane localization of the main basal-disk protein FlgP. With motility as a critical Campylobacter virulence factor, our work demonstrates that deletion of a small protein can bring a bacterial pathogen to a halt.

microbiology↗

Molecular model of a bacterial flagellar motor in situ reveals a "parts-list" of protein adaptations to increase torque

One hurdle to understanding how molecular machines work, and how they evolve, is our inability to see their structures in situ. Here we describe a minicell system that enables in situ cryogenic electron microscopy imaging and single particle analysis to investigate the structure of an iconic molecular machine, the bacterial flagellar motor, which spins a helical propeller for propulsion. We determine the structure of the high-torque Campylobacter jejuni motor in situ, including the subnanometre-resolution structure of the periplasmic scaffold, an adaptation essential to high torque. Our structure enables identification of new proteins, and interpretation with molecular models highlights origins of new components, reveals modifications of the conserved motor core, and explain how these structures both template a wider ring of motor proteins, and buttress the motor during swimming reversals. We also acquire insights into universal principles of flagellar torque generation. This approach is broadly applicable to other membrane-residing bacterial molecular machines complexes.

molecular biology↗