Abstract
ABSTRACTCampylobacter jejuni is a pathogenic bacterium that causes gastroenteritis in humans yet is a widespread commensal in wild and domestic animals, particularly poultry. Using RNA sequencing, we assessed C. jejuni transcriptional responses to medium supplemented with human fecal versus chicken cecal extracts and in extract-supplemented medium versus medium alone. C. jejuni exposed to extracts had altered expression of 40 genes related to iron uptake, metabolism, chemotaxis, energy production, and osmotic stress response. In human fecal versus chicken cecal extracts, C. jejuni displayed higher expression of genes involved in respiration (fdhTU) and in known or putative iron uptake systems (cfbpA, ceuB, chuC, and CJJ81176_1649–1655 [here designated 1649–1655]). The 1649–1655 genes and downstream overlapping gene 1656 were investigated further. Uncharacterized homologues of this system were identified in 33 diverse bacterial species representing 6 different phyla, 21 of which are associated with human disease. The 1649 and 1650 (p19) genes encode an iron transporter and a periplasmic iron binding protein, respectively; however, the role of the downstream 1651–1656 genes was unknown. A Δ1651–1656 deletion strain had an iron-sensitive phenotype, consistent with a previously characterized Δp19 mutant, and showed reduced growth in acidic medium, increased sensitivity to streptomycin, and higher resistance to H2O2 stress. In iron-restricted medium, the 1651–1656 and p19 genes were required for optimal growth when using human fecal extracts as an iron source. Collectively, this implicates a function for the 1649–1656 gene cluster in C. jejuni iron scavenging and stress survival in the human intestinal environment.
Highlights
IMPORTANCE Direct comparative studies of C. jejuni infection of a zoonotic commensal host and a disease-susceptible host are crucial to understanding the causes of infection outcome in humans
Among the differentially expressed genes, we selected one putative and as yet uncharacterized iron uptake gene cluster (CJJ81176_1649 –1656) for further study, as it was significantly more highly expressed during growth in medium with extracts compared to medium alone, and in particular in medium containing human fecal compared to chicken cecal extracts
C. jejuni cultured in medium containing chicken cecal or human fecal extracts compared to medium alone exhibited comparable levels of logarithmic growth, enhanced late-stage survival, and decreased biofilm formation
Summary
IMPORTANCE Direct comparative studies of C. jejuni infection of a zoonotic commensal host and a disease-susceptible host are crucial to understanding the causes of infection outcome in humans. The metabolomes of the chicken ceca and the human large intestine are expected to be dissimilar due to factors such as differences in diet, digestive system structure and function, host defense peptides, and the resident microbiome [20,21,22] These factors contribute to the availability of trace metals and micronutrients, such as iron, that are essential for bacterial cell growth and host colonization [23,24,25]. We compared phenotypic and gene expression differences in C. jejuni cells exposed to medium containing sterile intestinal extracts of the disease-susceptible host (humans) versus the commensal host (chickens). This work shows that C. jejuni responds differentially to metabolites present in the intestinal lumen of commensal versus susceptible hosts, provides a broad database repository of the C. jejuni transcriptional gene responses to these conditions, and shows that the 1649 –1656 iron uptake system participates in numerous key phenotypes and may be integral to host infection, especially in humans
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