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. 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.
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
David L
DL
Erickson
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Cynthia S
CS
Lew
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Brittany
B
Kartchner
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Nathan T
NT
Porter
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
S Wade
SW
McDaniel
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Nathan M
NM
Jones
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Sara
S
Mason
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Erin
E
Wu
Department of Microbiology and Molecular Biology, 4007 LSB, Brigham Young University, Provo, UT 84602, United States of America.
Eric
E
Wilson
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000235:genetics; D009876:Operon; D015011:Yersinia pseudotuberculosis / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D015012:Yersinia pseudotuberculosis Infections / Q000235:genetics / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C108074:CCL25 protein, human; C414047:CCL28 protein, human; D019742:Chemokines, CC; D008070:Lipopolysaccharides