Exploring the cytotoxic mechanisms of Pediocin PA-1 towards HeLa and HT29 cells by comparison to known bacteriocins: Microcin E492, enterocin heterodimer and Divercin V41.

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: Microcin E492, enterocin heterodimer and Divercin V41. PLoS ONE. 16 (9), p. e0251951. https://doi.org/10.1371/journal.pone.0251951
AuthorsBuss, G. and Wilson, C.
AbstractThe 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, Enterocin 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 whereas 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, due to the COVID-19 pandemic, we were unable to carry out experiments in the lab, and the unavailability of important data meant we were unable to provide and validate out solid conclusions, but rather suggestions. However, bioinformatic analysis is still able to provide information regarding structure and sequence analysis to draw plausible and evidence based conclusions. We have 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.
KeywordsHela Cells; HT29 Cells; Humans; Bacteriocins; Anti-Bacterial Agents; Apoptosis; Cell Survival; Amino Acid Sequence; Protein Conformation; Sequence Homology, Amino Acid; Models, Molecular; Toll-Like Receptor 4; Pandemics; Bridged-Ring Compounds; Pediocins; COVID-19; SARS-CoV-2
Year2021
JournalPLoS ONE
Journal citation16 (9), p. e0251951
PublisherCold Spring Harbor Laboratory
ISSN1932-6203
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0251951
Official URLhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251951
Publication dates
Online02 Sep 2021
Print01 Jan 2021
Publication process dates
Deposited09 Aug 2021
Output statusPublished
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