Role of Uropathogenic Escherichia coli Virulence Factors in Development of Urinary Tract Infection and Kidney Damage

Figure 1

Model of UPEC-induced signaling cascades in urothelial cells. Bacterial adherence to uroepithelium results in an epithelial inflammatory response including local production of chemokines and cytokines or cell death via apoptosis. Activation of TLR4 through virulence factors, including LPS and fimbriae, triggers the response, which involves activation of kinases and subsequent translocation of different transcriptional factors such as NF-κB, CREB, and IFR3 into the nucleus. HlyA (through LPS-LBP-CD14 complex) is delivered to the cell membrane and activates there GTPase RhoA, which is required for Ca²⁺ signaling. Specific HlyA-induced Ca²⁺ oscillations lead to activation of NF-κB and synthesis of IL6/IL-8. Chemokine production leads to recruitment of neutrophils that kill the bacteria by producing the cytotoxic substances. Tissue damage, cell death, and permanent scarring result in excessive inflammatory response.