Effects of the Escherichia coli small regulatory RNAs OmrA and OmrB on global transcription following growth in urine

Abstract

Urinary tract infections (UTIs) are common both in the US and worldwide, with 50-60% of women developing a UTI during their lifetime. The estimated cost of UTIs in the US is 3.5 billion dollars yearly. Approximately 70% - 90% of UTIs are caused by uropathogenic Escherichia coli (UPEC). UPEC differentially expresses a variety of genes to establish and maintain UTI in an osmotically stressful, urine-saturated environment. E. coli regulates some stress-related genes with small regulatory RNAs (sRNAs). Two sRNAs known to regulate UPEC virulence factors are OmrA and OmrB (OmrAB), which are expressed in high osmolarity conditions. To investigate genes regulated by OmrAB in UPEC grown in human urine, UPEC strains UTI89 and UTI89 ΔomrAB were grown in human urine and subjected to RNA sequencing and qRT-PCR analyses. Genes with significantly dysregulated transcript levels in UTI89 ΔomrAB were those involved in xylose transport/metabolism (i.e., xylA, xylR) as well as the nhaC and a malY homolog hypothetical protein genes, which encode a putative Na+ /H+ antiporter and a putative cystathionine β-lyase and maltose operon repressor, respectively. To investigate potential roles these genes have in UPEC survival in urine, UTI89 strains overexpressing xylR, nhaC, or the malY homolog were grown in human urine and compared to the parent strain. Overexpression of nhaC and the malY homolog significantly decreased and increased UTI89 growth in human urine, respectively. Additionally, overexpression of xylR had a minor inhibitory effect on UTI89 growth in human urine. These results indicate novel connections between OmrAB and metabolism and potential virulence factor genes, which could be useful in furthering the understanding of the UPEC transcriptome during a UTI as well as highlighting targets for antibacterial agents.