Iron uptake by Escherichia coli in urinary tract infections and urosepsis -- genetic and proteomic studies

Urinary tract infection caused by Escherichia coli can lead to urosepsis, and the pathogens’ effectiveness in acquiring iron determines their virulence. The level of expression of the siderophore genes in different environments (M9 medium, artificial urine, and M9 supplemented with blood) was investigated using the CAS assay and qPCR. Aerobactin was found much more frequently in blood than in urine isolates (P=0.03), but the expression in artificial urine was 2x higher than in blood (P=0.03). We observed significant changes in the expression of entC, iro-2, iucA, and iroB bacterial genes between groups in artificial urine. The siderophores enterobactin, aerobactin and yersiniabactin (P=0.016), with the iha and hlyA genes, may represent markers of increased urosepsis risk. Moreover, proteomic profiles between groups were significantly different (ferritin-1, iron uptake system component EfeO, ferrous iron transport protein B, nitrate/nitrite response regulator protein NarL, protein HemY, ferrienterobactin receptor FepA, lipopolysaccharide export system protein LptA and 2Fe-2S ferredoxin). We also observed the positive association with urosepsis of IL-6, TNF, and CRP proteins between groups. In conclusion, risk factors for UTI-related sepsis may be related to the iron uptake system, and genetic and proteomic profiles may help in their identification.