<p><i>Pseudomonas aeruginosa</i> is an opportunistically pathogenic bacteria that causes fatal infections and outbreaks in hospital environments. Due to the increasing prevalence of antibiotic-resistant strains of <i>P. aeruginosa</i>, the need for alternative therapies is critical. Bacteriophage therapy is emerging as a promising approach; however, it remains unapproved for clinical use and is hindered by limited understanding of the complex interactions between bacterial cells and phage virions. Mathematical models provide insight into these interactions. Through a system of ordinary differential equations, we successfully capture the dynamics observed between susceptible, infected, and mutated bacterial cells and bacteriophage virions in a microwell setting. Data fitting based on this model produced a set of parameter estimates unique to our experimental observations of a specific phage and <i>P. aeruginosa</i> strain. In translating observed optical density readings into bacterial concentrations, we also found that bacterial debris has a significant impact on optical density, with a lysed bacterium contributing roughly <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11538_2025_1478_Article_IEq1.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="31" /> </InlineMediaObject> <EquationSource Format="TEX">\({31\%}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mn>31</mn> <mo>%</mo> </mrow> </math></EquationSource> </InlineEquation> as much to optical density readings as a living cell.</p>

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A SIMPL Model of Phage-Bacteria Interactions Accounting for Mutation and Competition

  • Carli Peterson,
  • Darsh Gandhi,
  • Austin Carlson,
  • Aaron Lubkemann,
  • Emma Richardson,
  • John Serralta,
  • Michael S. Allen,
  • Souvik Roy,
  • Christopher M. Kribs,
  • Hristo V. Kojouharov

摘要

Pseudomonas aeruginosa is an opportunistically pathogenic bacteria that causes fatal infections and outbreaks in hospital environments. Due to the increasing prevalence of antibiotic-resistant strains of P. aeruginosa, the need for alternative therapies is critical. Bacteriophage therapy is emerging as a promising approach; however, it remains unapproved for clinical use and is hindered by limited understanding of the complex interactions between bacterial cells and phage virions. Mathematical models provide insight into these interactions. Through a system of ordinary differential equations, we successfully capture the dynamics observed between susceptible, infected, and mutated bacterial cells and bacteriophage virions in a microwell setting. Data fitting based on this model produced a set of parameter estimates unique to our experimental observations of a specific phage and P. aeruginosa strain. In translating observed optical density readings into bacterial concentrations, we also found that bacterial debris has a significant impact on optical density, with a lysed bacterium contributing roughly \({31\%}\) 31 % as much to optical density readings as a living cell.