Yersinia high pathogenicity island genes modify the Escherichia coli primary metabolome independently of siderophore production.
Bacterial siderophores may enhance pathogenicity by scavenging iron, but their expression has been proposed to exert a substantial metabolic cost. Here we describe a combined metabolomic-genetic approach to determine how mutations affecting the virulence-associated siderophore yersiniabactin affect the Escherichia coli primary metabolome. Contrary to expectations, we did not find yersiniabactin biosynthesis to correspond to consistent metabolomic shifts. Instead, we found that targeted deletion of ybtU or ybtA, dissimilar genes with similar roles in regulating yersiniabactin expression, were associated with a specific shift in arginine pathway metabolites during growth in minimal media. This interaction was associated with high arginine levels in the model uropathogen Escherichia coli UTI89 compared to its ybtU and ybtA mutants and the K12 strain MG1655, which lacks yersiniabactin-associated genes. Because arginine is not a direct yersiniabactin biosynthetic substrate, these findings show that virulence-associated secondary metabolite systems may shape bacterial primary metabolism independently of substrate consumption.
Center for Women's Infectious Diseases Research, Diabetic Cardiovascular Disease Center, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
Haitao
H
Lv
Jeffrey P
JP
Henderson
D001120:Arginine / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D016000:Cluster Analysis; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D044404:Genomic Islands; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D010636:Phenols / Q000302:isolation & purification / Q000378:metabolism; D017384:Sequence Deletion; D017262:Siderophores / Q000096:biosynthesis* / Q000235:genetics; D013844:Thiazoles / Q000302:isolation & purification / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015007:Yersinia / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; D015534:Trans-Activators; D014157:Transcription Factors; C103986:YbtA protein, Yersinia pestis; C412369:YbtU protein, Yersinia pestis; C104398:yersiniabactin; D001120:Arginine