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Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa
Here we formulate a mechanistic mathematical model to describe the growth dynamics of P. aeruginosa in the presence of the β-lactam antibiotic meropenem. The model is mechanistic in the sense that carrying capacity is taken into account through the dynamics of nutrient availability rather than via l...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843380/ https://www.ncbi.nlm.nih.gov/pubmed/29481562 http://dx.doi.org/10.1371/journal.pcbi.1006012 |
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author | Spalding, Chloe Keen, Emma Smith, David J. Krachler, Anne-Marie Jabbari, Sara |
author_facet | Spalding, Chloe Keen, Emma Smith, David J. Krachler, Anne-Marie Jabbari, Sara |
author_sort | Spalding, Chloe |
collection | PubMed |
description | Here we formulate a mechanistic mathematical model to describe the growth dynamics of P. aeruginosa in the presence of the β-lactam antibiotic meropenem. The model is mechanistic in the sense that carrying capacity is taken into account through the dynamics of nutrient availability rather than via logistic growth. In accordance with our experimental results we incorporate a sub-population of cells, differing in morphology from the normal bacillary shape of P. aeruginosa bacteria, which we assume have immunity from direct antibiotic action. By fitting this model to experimental data we obtain parameter values that give insight into the growth of a bacterial population that includes different cell morphologies. The analysis of two parameters sets, that produce different long term behaviour, allows us to manipulate the system theoretically in order to explore the advantages of a shape transition that may potentially be a mechanism that allows P. aeruginosa to withstand antibiotic effects. Our results suggest that inhibition of this shape transition may be detrimental to bacterial growth and thus suggest that the transition may be a defensive mechanism implemented by bacterial machinery. In addition to this we provide strong theoretical evidence for the potential therapeutic strategy of using antimicrobial peptides (AMPs) in combination with meropenem. This proposed combination therapy exploits the shape transition as AMPs induce cell lysis by forming pores in the cytoplasmic membrane, which becomes exposed in the spherical cells. |
format | Online Article Text |
id | pubmed-5843380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58433802018-03-23 Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa Spalding, Chloe Keen, Emma Smith, David J. Krachler, Anne-Marie Jabbari, Sara PLoS Comput Biol Research Article Here we formulate a mechanistic mathematical model to describe the growth dynamics of P. aeruginosa in the presence of the β-lactam antibiotic meropenem. The model is mechanistic in the sense that carrying capacity is taken into account through the dynamics of nutrient availability rather than via logistic growth. In accordance with our experimental results we incorporate a sub-population of cells, differing in morphology from the normal bacillary shape of P. aeruginosa bacteria, which we assume have immunity from direct antibiotic action. By fitting this model to experimental data we obtain parameter values that give insight into the growth of a bacterial population that includes different cell morphologies. The analysis of two parameters sets, that produce different long term behaviour, allows us to manipulate the system theoretically in order to explore the advantages of a shape transition that may potentially be a mechanism that allows P. aeruginosa to withstand antibiotic effects. Our results suggest that inhibition of this shape transition may be detrimental to bacterial growth and thus suggest that the transition may be a defensive mechanism implemented by bacterial machinery. In addition to this we provide strong theoretical evidence for the potential therapeutic strategy of using antimicrobial peptides (AMPs) in combination with meropenem. This proposed combination therapy exploits the shape transition as AMPs induce cell lysis by forming pores in the cytoplasmic membrane, which becomes exposed in the spherical cells. Public Library of Science 2018-02-26 /pmc/articles/PMC5843380/ /pubmed/29481562 http://dx.doi.org/10.1371/journal.pcbi.1006012 Text en © 2018 Spalding et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Spalding, Chloe Keen, Emma Smith, David J. Krachler, Anne-Marie Jabbari, Sara Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa |
title | Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa |
title_full | Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa |
title_fullStr | Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa |
title_full_unstemmed | Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa |
title_short | Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa |
title_sort | mathematical modelling of the antibiotic-induced morphological transition of pseudomonas aeruginosa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843380/ https://www.ncbi.nlm.nih.gov/pubmed/29481562 http://dx.doi.org/10.1371/journal.pcbi.1006012 |
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