Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa

Chloe Spalding, Emma Keen, David J Smith, Anne-Marie Krachler, Sara Jabbari

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
273 Downloads (Pure)


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.

Original languageEnglish
Article numbere1006012
Number of pages28
JournalPLoS Computational Biology
Issue number2
Publication statusPublished - 26 Feb 2018


Dive into the research topics of 'Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa'. Together they form a unique fingerprint.

Cite this