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Updated: Aug 19, 2026

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Effect of Staphylococcus aureus bacteria and bacterial toxins on meningeal permeability in vitro
W C Ummenhofer1, A E Stapleton, C M Bernards
1Department of Anesthesiology, University of Washington, Seattle 98195, USA.
Background And Objectives:
Epidural catheterization is associated with a significant bacterial colonization rate and occasionally frank infection. During epidural space infection, decreased analgesia despite increased epidural opioid doses has been described. One possible explanation for this observation is that bacterial infection decreases meningeal permeability. The purpose of the study was to determine whether Staphylococcus aureus bacteria, the most common organism causing epidural space infection, or S. aureus toxins alter meningeal permeability.
Methods:
Spinal meninges of M. nemestrina monkeys were mounted in a previously established in vitro diffusion cell model and exposed to S. aureus toxins A, B, and F. Simultaneous transmeningeal fluxes of mannitol and sufentanil were measured before and after toxin exposure and compared to controls. In a second series of experiments, diffusion cells were inoculated with live S. aureus bacteria in suspension and the permeability of sufentanil was investigated.
Results:
Staphylococcus aureus toxin-A increased the transmeningeal flux of mannitol but not sufentanil. Toxins B and F did not alter the meningeal permeability of either drug. Inoculation with live S. aureus bacteria increased the transmeningeal flux of sufentanil by 115+/-21% (P = .032).
Conclusions:
These data demonstrate that S. aureus alpha-toxin and live S. aureus bacteria can increase meningeal permeability. Thus, clinical observations of decreased epidural analgesia in the face of bacterial infection cannot be explained by decreased meningeal permeability.
Insights
Bacterial infection, specifically Staphylococcus aureus, can increase meningeal permeability, potentially affecting drug delivery during epidural procedures. This finding challenges previous explanations for reduced pain relief in infected patients.
Area of Science:
- Neuroscience
- Infectious Disease Research
- Pharmacology
Background:
- Epidural catheterization carries a risk of bacterial colonization and infection.
- Reduced analgesia during epidural infections is often observed despite increased opioid doses.
- Decreased meningeal permeability has been hypothesized as a cause for reduced drug efficacy.
Purpose of the Study:
- To investigate the impact of Staphylococcus aureus and its toxins on meningeal permeability.
- To determine if bacterial infection alters the barrier function of the spinal meninges.
Main Methods:
- Utilized an in vitro diffusion cell model with spinal meninges from M. nemestrina monkeys.
- Exposed meninges to Staphylococcus aureus toxins A, B, and F, measuring mannitol and sufentanil fluxes.
- Inoculated diffusion cells with live Staphylococcus aureus to assess sufentanil permeability.
Main Results:
- Staphylococcus aureus toxin-A increased mannitol flux but not sufentanil flux across the meninges.
- Toxins B and F did not affect meningeal permeability to mannitol or sufentanil.
- Live Staphylococcus aureus significantly increased sufentanil permeability by 115%.
Conclusions:
- Staphylococcus aureus alpha-toxin and live bacteria can enhance meningeal permeability.
- The observed increase in permeability suggests that decreased drug efficacy during infection is not due to a tighter meningeal barrier.
- This study provides a new understanding of the interaction between bacterial infection and drug transport in the epidural space.
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