UropathogenicEscherichia colivirulence factor hemolysin A causes programmed cell necrosis by altering mitochondrial dynamics

What is it about?

Bacterial infections eliciting epididymo-orchitis could cause male infertility with uropathogenic Escherichia coli (UPEC) as a relevant pathogen. In our earlier study, we have demonstrated that necrosis was the dominant cell death pathway in UPEC-infected rat testis, and necrotic changes were observed in testicular somatic cells namely Sertoli cells (SC) and peritubular cells (PTC). Hence, in this study we delineate the molecular mechanisms of necrotic cell death pathways in these cells. Mitochondria are highly energetic cell organelles that play a central role in activation of cell death pathways. In this study, we have shown that UPEC did not induce apoptosis, pyroptosis and necroptosis cell death pathways, but instead, induced programmed cell necrosis death pathway in SC and PTC. UPEC virulence factor HlyA impairs the dynamics and function of mitochondria that resulted in an increase in the intracellular level of calcium, fragmentation of mitochondria, ATP depletion, and finally the passive release of danger associated molecular patterns (DAMPs) such as HMGB1 and Histone 3. Moreover, the released DAMPs provoked an inflammatory response in TM. In summary, UPEC infection induces necrotic cell death and activates inflammatory immune responses that could provide a rationale explaining why approximately 40% of males become infertile following UPEC infection, despite antibacterial therapy eradicating the pathogen.

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