Lipopolysaccharide Biosynthesis Genes of Yersinia pseudotuberculosis Promote Resistance to Antimicrobial Chemokines

Antimicrobial chemokines (AMCs) are a recently described family of host defense peptides that play an important role in protecting a wide variety of organisms from bacterial infection. Very little is known about the bacterial targets of AMCs or factors that influence bacterial susceptibility to AMCs...

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Published in:	PloS one Vol. 11; no. 6; p. e0157092
Main Authors:	Erickson, David L, Lew, Cynthia S, Kartchner, Brittany, Porter, Nathan T, McDaniel, S Wade, Jones, Nathan M, Mason, Sara, Wu, Erin, Wilson, Eric
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 08-06-2016 Public Library of Science (PLoS)
Subjects:	Adenosine diphosphate Analysis Antigens Antiinfectives and antibacterials Antimicrobial activity Antimicrobial agents Antimicrobial Cationic Peptides - pharmacology Bacteria Binding Biology and Life Sciences Biosynthesis Carbohydrates Cell death Cell surface Chemokines Chemokines, CC - pharmacology Drug Resistance, Bacterial Genes Genetic aspects Gram-positive bacteria Haemophilus influenzae Heptose Humans Infections Killing Lipids Lipopolysaccharides Lipopolysaccharides - biosynthesis Lipopolysaccharides - genetics Medicine and Health Sciences Molecular biology Mutagenesis Mutants Neutrophils Oligosaccharides Operon Oxidation Pathogens Peptides Proteins Pseudotuberculosis Shielding Temperature Transposons Yersinia Yersinia pestis Yersinia pseudotuberculosis Yersinia pseudotuberculosis - enzymology Yersinia pseudotuberculosis - genetics Yersinia pseudotuberculosis - growth & development Yersinia pseudotuberculosis Infections - genetics Yersinia pseudotuberculosis Infections - metabolism United States > US
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Summary:	Antimicrobial chemokines (AMCs) are a recently described family of host defense peptides that play an important role in protecting a wide variety of organisms from bacterial infection. Very little is known about the bacterial targets of AMCs or factors that influence bacterial susceptibility to AMCs. In an effort to understand how bacterial pathogens resist killing by AMCs, we screened Yersinia pseudotuberculosis transposon mutants for those with increased binding to the AMCs CCL28 and CCL25. Mutants exhibiting increased binding to AMCs were subjected to AMC killing assays, which revealed their increased sensitivity to chemokine-mediated cell death. The majority of the mutants exhibiting increased binding to AMCs contained transposon insertions in genes related to lipopolysaccharide biosynthesis. A particularly strong effect on susceptibility to AMC mediated killing was observed by disruption of the hldD/waaF/waaC operon, necessary for ADP-L-glycero-D-manno-heptose synthesis and a complete lipopolysaccharide core oligosaccharide. Periodate oxidation of surface carbohydrates also enhanced AMC binding, whereas enzymatic removal of surface proteins significantly reduced binding. These results suggest that the structure of Y. pseudotuberculosis LPS greatly affects the antimicrobial activity of AMCs by shielding a protein ligand on the bacterial cell surface.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Current address: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, United States of America Conceived and designed the experiments: DLE E. Wilson CSL. Performed the experiments: CSL BK NTP SM E. Wu. Analyzed the data: DLE CSL SM E. Wilson. Contributed reagents/materials/analysis tools: SWM NMJ. Wrote the paper: DLE CSL SM E. Wilson.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0157092