Heterogenous biofilm mass-transport model replicates periphery sequestration of antibiotics in Pseudomonas aeruginosa PAO1 microcolonies

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 47; p. e2312995120
• Main Authors: Prince, Joshua, Jones, A-Andrew D.
• Format: Journal Article
• Language: English
• Published: 21-11-2023
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2312995120

A model for antibiotic accumulation in bacterial biofilm microcolonies utilizing heterogenous porosity and attachment site profiles replicated the periphery sequestration reported in prior experimental studies on
Pseudomonas aeruginosa PAO1
biofilm cell clusters. These
P. aeruginosa
cell clusters are in vitro models of the chronic
P. aeruginosa
infections in cystic fibrosis patients which display recalcitrance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics fail to penetrate biofilm cell clusters. The physical phenomena driving this periphery sequestration have not been definitively established. This paper introduces mathematical models to account for two proposed physical phenomena driving periphery sequestration: biofilm matrix attachment and volume-exclusion due to variable biofilm porosity. An antibiotic accumulation model which incorporated these phenomena better fit observed periphery sequestration data compared to previous models.