Binding of Phage-Encoded FlaGrab to Motile Campylobacter jejuni Flagella Inhibits Growth, Downregulates Energy Metabolism, and Requires Specific Flagellar Glycans
Abstract
Many bacterial pathogens display glycosylated surface structures that contribute to virulence, and targeting these structures is a viable strategy for pathogen control. The foodborne pathogen Campylobacter jejuni expresses a vast diversity of flagellar glycans, and flagellar glycosylation is essential for its virulence. Little is known about why C. jejuni encodes such a diverse set of flagellar glycans, but it has been hypothesized that evolutionary pressure from bacteriophages (phages) may have contributed to this diversity. However, interactions between Campylobacter phages and host flagellar glycans have not been characterized in detail. Previously, we observed that Gp047 (now renamed FlaGrab), a conserved Campylobacter phage protein, binds to C. jejuni flagella displaying the nine-carbon monosaccharide 7-acetamidino-pseudaminic acid, and that this binding partially inhibits cell growth. However, the mechanism of this growth inhibition, as well as how C. jejuni might resist this activity, are not well-understood. Here we use RNA-Seq to show that FlaGrab exposure leads C. jejuni 11168 cells to downregulate expression of energy metabolism genes, and that FlaGrab-induced growth inhibition is dependent on motile flagella. Our results are consistent with a model whereby FlaGrab binding transmits a signal through flagella that leads to retarded cell growth. To evaluate mechanisms of FlaGrab resistance inmore »
- Authors:
- Publication Date:
- Research Org.:
- Univ. of Georgia, Athens, GA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1605607
- Alternate Identifier(s):
- OSTI ID: 1802757
- Grant/Contract Number:
- SC0015662
- Resource Type:
- Published Article
- Journal Name:
- Frontiers in Microbiology
- Additional Journal Information:
- Journal Name: Frontiers in Microbiology Journal Volume: 11; Journal ID: ISSN 1664-302X
- Publisher:
- Frontiers Media SA
- Country of Publication:
- Switzerland
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Microbiology; bacteriophages; Campylobacter jejuni; flagella; protein glycosylation; pseudaminic acid; mass spectrometry; motility; bacterial surface structures
Citation Formats
Sacher, Jessica C., Shajahan, Asif, Butcher, James, Patry, Robert T., Flint, Annika, Hendrixson, David R., Stintzi, Alain, Azadi, Parastoo, and Szymanski, Christine M. Binding of Phage-Encoded FlaGrab to Motile Campylobacter jejuni Flagella Inhibits Growth, Downregulates Energy Metabolism, and Requires Specific Flagellar Glycans. Switzerland: N. p., 2020.
Web. doi:10.3389/fmicb.2020.00397.
Sacher, Jessica C., Shajahan, Asif, Butcher, James, Patry, Robert T., Flint, Annika, Hendrixson, David R., Stintzi, Alain, Azadi, Parastoo, & Szymanski, Christine M. Binding of Phage-Encoded FlaGrab to Motile Campylobacter jejuni Flagella Inhibits Growth, Downregulates Energy Metabolism, and Requires Specific Flagellar Glycans. Switzerland. https://doi.org/10.3389/fmicb.2020.00397
Sacher, Jessica C., Shajahan, Asif, Butcher, James, Patry, Robert T., Flint, Annika, Hendrixson, David R., Stintzi, Alain, Azadi, Parastoo, and Szymanski, Christine M. Fri .
"Binding of Phage-Encoded FlaGrab to Motile Campylobacter jejuni Flagella Inhibits Growth, Downregulates Energy Metabolism, and Requires Specific Flagellar Glycans". Switzerland. https://doi.org/10.3389/fmicb.2020.00397.
@article{osti_1605607,
title = {Binding of Phage-Encoded FlaGrab to Motile Campylobacter jejuni Flagella Inhibits Growth, Downregulates Energy Metabolism, and Requires Specific Flagellar Glycans},
author = {Sacher, Jessica C. and Shajahan, Asif and Butcher, James and Patry, Robert T. and Flint, Annika and Hendrixson, David R. and Stintzi, Alain and Azadi, Parastoo and Szymanski, Christine M.},
abstractNote = {Many bacterial pathogens display glycosylated surface structures that contribute to virulence, and targeting these structures is a viable strategy for pathogen control. The foodborne pathogen Campylobacter jejuni expresses a vast diversity of flagellar glycans, and flagellar glycosylation is essential for its virulence. Little is known about why C. jejuni encodes such a diverse set of flagellar glycans, but it has been hypothesized that evolutionary pressure from bacteriophages (phages) may have contributed to this diversity. However, interactions between Campylobacter phages and host flagellar glycans have not been characterized in detail. Previously, we observed that Gp047 (now renamed FlaGrab), a conserved Campylobacter phage protein, binds to C. jejuni flagella displaying the nine-carbon monosaccharide 7-acetamidino-pseudaminic acid, and that this binding partially inhibits cell growth. However, the mechanism of this growth inhibition, as well as how C. jejuni might resist this activity, are not well-understood. Here we use RNA-Seq to show that FlaGrab exposure leads C. jejuni 11168 cells to downregulate expression of energy metabolism genes, and that FlaGrab-induced growth inhibition is dependent on motile flagella. Our results are consistent with a model whereby FlaGrab binding transmits a signal through flagella that leads to retarded cell growth. To evaluate mechanisms of FlaGrab resistance in C. jejuni, we characterized the flagellar glycans and flagellar glycosylation loci of two C. jejuni strains naturally resistant to FlaGrab binding. Our results point toward flagellar glycan diversity as the mechanism of resistance to FlaGrab. Overall, we have further characterized the interaction between this phage-encoded flagellar glycan-binding protein and C. jejuni, both in terms of mechanism of action and mechanism of resistance. Our results suggest that C. jejuni encodes as-yet unidentified mechanisms for generating flagellar glycan diversity, and point to phage proteins as exciting lenses through which to study bacterial surface glycans.},
doi = {10.3389/fmicb.2020.00397},
journal = {Frontiers in Microbiology},
number = ,
volume = 11,
place = {Switzerland},
year = {2020},
month = {3}
}
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