Alpha-haemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells

Area of Science:

• Nephrology
• Microbiology
• Cell Biology

Background:

• Pyelonephritis, a common childhood febrile illness, can lead to irreversible kidney damage and end-stage renal failure.
• Renal scarring may occur without inflammatory cells, suggesting direct bacterial signaling impacts renal cells.
• Intracellular calcium ([Ca2+]i) oscillations protect cells from calcium toxicity, but the inducing proteins remain unidentified.

Purpose of the Study:

• To identify the bacterial protein responsible for inducing intracellular calcium oscillations in renal epithelial cells during infection.
• To elucidate the mechanism by which uropathogenic Escherichia coli affects renal cells and contributes to pyelonephritis.

Main Methods:

• Primary rat renal epithelial cells and a renal epithelial cell line were infected with uropathogenic Escherichia coli.
• Intracellular calcium ([Ca2+]i) oscillations were measured.
• The role of L-type calcium channels and internal calcium stores was investigated.
• Cytokine production (interleukin-6 and -8) was assessed.

Main Results:

• Uropathogenic Escherichia coli infection induced low-frequency oscillatory [Ca2+]i responses in renal epithelial cells.
• The RTX toxin alpha-haemolysin was identified as the inducer of these calcium oscillations.
• Calcium influx via L-type calcium channels and internal stores gated by inositol triphosphate were crucial for the response.
• Alpha-haemolysin-induced calcium oscillations stimulated the production of interleukin-6 and -8.

Conclusions:

• Alpha-haemolysin is a novel virulence factor in pyelonephritis that induces specific intracellular calcium oscillations.
• These oscillations fine-tune gene expression, modulating the inflammatory response in renal cells.
• The findings suggest a new mechanism for bacterial-induced renal damage and highlight alpha-haemolysin as a potential therapeutic target.