Antibiotics select for novel pathways of resistance in biofilms

Most bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is uncle...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Trampari, Eleftheria, Holden, Emma R, Wickham, Gregory J, Ravi, Anuradha, Prischi, Filippo, De-Oliviera-Martins, Leonardo, Savva, George M, Bavro, Vassiliy N, Webber, Mark
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 10.04.2019
Subjects
Adaptation
Antibiotic resistance
Antibiotics
Azithromycin
Bacteria
Biofilms
Cefotaxime
Cell culture
Evolution
Liquid culture
Phenotypes
Reproductive fitness
Online AccessGet full text

Cover

More Information
Summary:Most bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is unclear whether biofilms adapt and evolve in response to sub-inhibitory concentrations of drugs. Here we used a biofilm evolution model to show that biofilms of a model food borne pathogen, Salmonella Typhimurium rapidly evolve in response to exposure to three clinically important antibiotics. Whilst the model strongly selected for improved biofilm formation in the absence of any drug, once antibiotics were introduced the need to adapt to the drug was more important than the selection for improved biofilm formation. Adaptation to antibiotic stress imposed a marked cost in biofilm formation, particularly evident for populations exposed to cefotaxime and azithromycin. We identified distinct resistance phenotypes in biofilms compared to corresponding planktonic control cultures and characterised new mechanisms of resistance to cefotaxime and azithromycin. Novel substitutions within the multidrug efflux transporter, AcrB were identified and validated as impacting drug export as well as changes in regulators of this efflux system. There were clear fitness costs identified and associated with different evolutionary trajectories. Our results demonstrate that biofilms adapt rapidly to low concentrations of antibiotics and the mechanisms of adaptation are novel. This work will be a starting point for studies to further examine biofilm specific pathways of adaptation which inform future antibiotic use.
DOI:10.1101/605212