Exploring the cytotoxic mechanisms of Pediocin PA-1 towards HeLa and HT29 cells by comparison to known bacteriocins

Journal article


Buss, G. and Wilson, C. 2021. Exploring the cytotoxic mechanisms of Pediocin PA-1 towards HeLa and HT29 cells by comparison to known bacteriocins. bioRxiv. https://doi.org/10.1101/2021.05.07.443071
AuthorsBuss, G. and Wilson, C.
Abstract

The purpose of this study was to explore potential mechanisms of cytotoxicity towards HeLa and HT29 cells displayed by Pediocin PA-1. We did this by carrying out sequence alignments and 3D modelling of related bacteriocins which have been studied in greater detail: Microcin E492, Eneterocin AB heterodimer and Divercin V41. Microcin E492 interacts with Toll-Like Receptor 4 in order to activate an apoptosis reaction, sequence alignment showed a high homology between Pediocin PA-1 and Microcin E492 and 3D modelling showed Pediocin PA-1 interacting with TLR-4 in a way reminiscent of Microcin E492. Furthermore, Pediocin PA-1 had the highest homology with the Enterocin heterodimer, particularly chain A; Enterocin has also shown to cause an apoptotic response in cancer cells. Based on this we are led to strongly believe Pediocin PA-1 interacts with TLRs in order to cause cell death. If this is the case it would explain the difference in cytotoxicity towards HeLa over HT29 cells, due to difference in expression of particular TLRs.

Overall, we believe Pediocin PA-1 exhibits a dual effect which is dose dependant, like that of Microcin. Unfortunately, the COVID-19 pandemic meant that we were unable to carry out experiments in the lab, and the unavailability of important data meant we were unable to make solid conclusions but rather suggestions. However despite this we have still been able to highlight interesting findings and how these could be translated into future research and therapeutics in order to improve the quality of treatment and life of cancer patients.

KeywordsCytotoxicity ; Biology
Year2021
JournalbioRxiv
PublisherCold Spring Harbour Laboratory Press
Digital Object Identifier (DOI)https://doi.org/10.1101/2021.05.07.443071
Official URLhttps://www.biorxiv.org/content/10.1101/2021.05.07.443071v1
Publication dates
Online07 May 2021
Publication process dates
Deposited09 Aug 2021
Publisher's version
License
Output statusIn press
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This is a pre-print.

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