Bioinformatic Analysis of Toll-Like Receptor Sequences and Structures

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 ◽

10.1371/journal.pone.0251951 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0251951

Author(s):

George P. Buss ◽

Cornelia M. Wilson

Keyword(s):

Bioinformatic Analysis ◽

3D Modelling ◽

Future Research ◽

Toll Like Receptor ◽

Sequence Alignments ◽

Toll Like Receptor 4 ◽

Dual Effect ◽

Ht29 Cells ◽

The Difference

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, 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.

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Bioinformatic Analysis of Toll-Like Receptor Sequences and Structures

Methods in Molecular Biology - Toll-Like Receptors ◽

10.1007/978-1-4939-3335-8_2 ◽

2016 ◽

pp. 29-39 ◽

Cited By ~ 2

Author(s):

Tom P. Monie ◽

Nicholas J. Gay ◽

Monique Gangloff

Keyword(s):

Bioinformatic Analysis ◽

Toll Like Receptor

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Induction of a Novel Chicken Toll-Like Receptor following Salmonella enterica Serovar Typhimurium Infection

Infection and Immunity ◽

10.1128/iai.74.3.1692-1698.2006 ◽

2006 ◽

Vol 74 (3) ◽

pp. 1692-1698 ◽

Cited By ~ 128

Author(s):

Rowan Higgs ◽

Paul Cormican ◽

Sarah Cahalane ◽

Brenda Allan ◽

Andrew T. Lloyd ◽

...

Keyword(s):

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Bioinformatic Analysis ◽

Innate Immune ◽

Toll Like Receptor ◽

Tlr2 Expression ◽

Embryonic Fibroblasts ◽

Serovar Typhimurium

ABSTRACT Toll-like receptors (TLRs) are a group of highly conserved molecules that initiate the innate immune response to pathogens by recognizing structural motifs expressed by microbes. We have identified a novel TLR, TLR15, by bioinformatic analysis of the chicken genome, which is distinct from any known vertebrate TLR and thus appears to be avian specific. The gene for TLR15 was sequenced and is found on chromosome 3, and it has archetypal TIR and transmembrane domains and a distinctive arrangement of extracellular leucine-rich regions. mRNA for TLR15 was detected in the spleen, bursa, and bone marrow of healthy chickens, suggesting a role for this novel receptor in constitutive host defense. Following in vivo Salmonella enterica serovar Typhimurium infection, quantitative real-time PCR demonstrated significant upregulation of TLR15 in the cecum of infected chickens. Interestingly, similar induction of TLR2 expression following infection was also observed. In vitro studies revealed TLR15 upregulation in chicken embryonic fibroblasts stimulated with heat-killed S. enterica serovar Typhimurium. Collectively, these results suggest a role for the TLR in avian defense against bacterial infection. We hypothesize that TLR15 may represent an avian-specific TLR that has been either retained in chicken and lost in other taxa or gained in the chicken.

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