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Microbiology Society logo Microbiology

Volume 170, Issue 8

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia Open Access

Abstract

Ventilator-associated pneumonia is defined as pneumonia that develops in a patient who has been on mechanical ventilation for more than 48 hours through an endotracheal tube. It is caused by biofilm formation on the indwelling tube, which introduces pathogenic microbes such as , and into the patient’s lower airways. Currently, there is a lack of accurate models of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates the biofilm formation of these pathogens in a host-mimicking environment and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilated airway mucus medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-scanning electron microscopy were employed to characterize the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved the biofilm eradication of all pathogens. Our endotracheal tube model informs on fundamental microbiology in the ventilator-associated pneumonia context and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antimicrobial resistance , antimicrobial tolerance , biofilm , endotracheal tube , hospital-acquired infection and infection
Funding
This study was supported by the:
  • Monash-Warwick Alliance
    • Principle Award Recipient: FreyaHarrison
  • Monash-Warwick Alliance
    • Principle Award Recipient: AnaTraven
  • Monash-Warwick Alliance
    • Principle Award Recipient: TrevorLithgow
  • University of Warwick
    • Principle Award Recipient: DeanWalsh
  • Australian Research Council (Award FT190100733)
    • Principle Award Recipient: AnaTraven
  • Australian NHMRC (Award 2016330)
    • Principle Award Recipient: TrevorLithgow
  • ESPRC (Award EP/S021434/1)
    • Principle Award Recipient: ChrisParmenter
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2024-08-01
2025-07-16
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/content/journal/micro/10.1099/mic.0.001480
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A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia
Microbiology 170, 001480 (2024); https://doi.org/10.1099/mic.0.001480
/content/journal/micro/10.1099/mic.0.001480
/content/journal/micro/10.1099/mic.0.001480
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