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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...

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Autores principales: Spalding, Chloe, Keen, Emma, Smith, David J., Krachler, Anne-Marie, Jabbari, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
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.
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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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