Introduction: Urinary tract infections are predominantly caused by a phylogenetically diverse group of uropathogenic E. coli (UPEC) strains. An ordered and conserved sequence of events that includes entry into and replication within uroepithelial cells implies a common infection mechanism, but numerous and extensive genomic analyses have failed to identify a common set of UPEC virulence genes. A recent consensus hypothesizes that virulence involves elevated expression of core genes (present in all E. coli strains), but recent transcriptomics studies have failed to identify these genes. We compared transcriptomes from UPEC and non-pathogenic E. coli (NPEC) strains from three distinct phylogenetic groups, and results suggest that UPEC are derived from NPEC strains, but are genetically distinct, and that UPEC strains share a common genetic program.
Methods: RNA was isolated from mid- to late-log bacterial cultures, transcribed to DNA, and sequenced through Illumina sequencing. The sequence results identified differentially expressed genes between 9 NPEC and 9 UPEC strains, and between 3 NPEC and 3 UPEC strains within 3 different phylogenetic groups.
Results: Common features of UPEC strains were upregulation of genes for the magnesium-sensing PhoP regulon and unfolded protein stress response, and downregulation of genes coding for ribosomal proteins and purine synthesis enzymes. Variation in gene expression patterns was large, and some UPEC strains had unusual transcription patterns, such as high expression of exopolysaccharide synthesis genes that may represent a virulence strategy to evade innate immunity.
Conclusions: The differentially expressed genes suggest that UPEC strains have undergone a survival bottleneck that results in upregulation of PhoP regulon genes and activation of the stringent response which downregulates the translational machinery in response to different stresses. During an infection, few bacteria are internalized into epithelial cells, and few of these bacteria replicate within these cells. We propose that the UPEC transcriptomic pattern describes the mechanism required to survive a viability-threatening environment that could be passage through and exit from intracellular vesicles such as lysosomes. The expressed genes suggest a basis for innate immunity evasion and antibiotic resistance. We note that the UPEC gene expression pattern has been observed for another intracellular pathogen.
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