Enterohemolysin

Last updated

Enterohemolysin, also known as EHEC-Hly or Ehx, is a bacterial toxin and a significant virulence factor produced by enterohemorrhagic Escherichia coli (EHEC). [1] [2] It belongs to the Repeats-in-Toxin (RTX) family of pore-forming proteins. The genetic instructions for producing enterohemolysin are located on a large plasmid within the bacteria in an operon designated EHEC-hlyCABD. [1]

This toxin plays a role in the tissue damage observed during EHEC infections, which can lead to severe illnesses such as hemorrhagic colitis and hemolytic-uremic syndrome (HUS). [2] Enterohemolysin exists in two biologically active forms: a free, soluble form and another form associated with outer membrane vesicles (OMVs) released by the bacteria. [1] The OMV-associated form is more stable and has a prolonged hemolytic effect compared to the free toxin. [3] The free form of EHEC-Hly lyses human microvascular endothelial cells by creating pores in the cell membrane. In contrast, the OMV-associated form does not lyse these cells but instead enters them, targets the mitochondria, and induces programmed cell death (apoptosis). [4] Furthermore, EHEC-Hly can stimulate an inflammatory response by prompting human monocytes and macrophages to release interleukin-1β. [5] [6]

See also

References

  1. 1 2 3 Bielaszewska M, Aldick T, Bauwens A, Karch H (July 2014). "Hemolysin of enterohemorrhagic Escherichia coli: structure, transport, biological activity and putative role in virulence". Int J Med Microbiol. 304 (5–6): 521–9. doi:10.1016/j.ijmm.2014.05.005. PMID   24933303.
  2. 1 2 Schwidder M, Heinisch L, Schmidt H (August 2019). "Genetics, Toxicity, and Distribution of Enterohemorrhagic Escherichia coli Hemolysin". Toxins (Basel). 11 (9): 502. doi: 10.3390/toxins11090502 . PMC   6784236 . PMID   31470552.
  3. Aldick T, Bielaszewska M, Uhlin BE, Humpf HU, Wai SN, Karch H (March 2009). "Vesicular stabilization and activity augmentation of enterohaemorrhagic Escherichia coli haemolysin". Mol Microbiol. 71 (6): 1496–508. doi:10.1111/j.1365-2958.2009.06618.x. PMID   19210618.
  4. Bielaszewska M, Rüter C, Kunsmann L, Greune L, Bauwens A, Zhang W, Kuczius T, Kim KS, Mellmann A, Schmidt MA, Karch H (2013). "Enterohemorrhagic Escherichia coli hemolysin employs outer membrane vesicles to target mitochondria and cause endothelial and epithelial apoptosis". PLOS Pathog. 9 (12): e1003797. doi: 10.1371/journal.ppat.1003797 . PMC   3861543 . PMID   24348251.
  5. Taneike I, Zhang HM, Wakisaka-Saito N, Yamamoto T (July 2002). "Enterohemolysin operon of Shiga toxin-producing Escherichia coli: a virulence function of inflammatory cytokine production from human monocytes". FEBS Lett. 524 (1–3): 219–24. Bibcode:2002FEBSL.524..219T. doi:10.1016/s0014-5793(02)03027-2. PMID   12135770.
  6. Zhang X, Cheng Y, Xiong Y, Ye C, Zheng H, Sun H, Zhao H, Ren Z, Xu J (2012). "Enterohemorrhagic Escherichia coli specific enterohemolysin induced IL-1β in human macrophages and EHEC-induced IL-1β required activation of NLRP3 inflammasome". PLOS ONE. 7 (11): e50288. Bibcode:2012PLoSO...750288Z. doi: 10.1371/journal.pone.0050288 . PMC   3507778 . PMID   23209696.