Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes

Dani A. C. Heesterbeek, Remy M. Muts, Vincent P. van Hensbergen, Pieter de Saint Aulaire, View ORCID ProfileTom Wennekes, Bart W. Bardoel, Nina M. van Sorge, View ORCID ProfileSuzan H.M. Rooijakkers
doi: https://doi.org/10.1101/2020.01.28.923243
Dani A. C. Heesterbeek
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Remy M. Muts
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent P. van Hensbergen
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pieter de Saint Aulaire
2Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tom Wennekes
2Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tom Wennekes
Bart W. Bardoel
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nina M. van Sorge
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Suzan H.M. Rooijakkers
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Suzan H.M. Rooijakkers
  • For correspondence: S.H.M.Rooijakkers@umcutrecht.nl
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Infections with Gram-negative bacteria form an increasing risk for human health, which is mainly due to the increase in antibiotic resistance. The cell envelope of Gram-negative bacteria consists of an inner membrane, a peptidoglycan layer and an outer membrane, which forms an impermeable barrier to many antibiotics and antimicrobial proteins. The complement system is an important factor of the human immune system that can efficiently kill Gram-negative bacteria via the formation of large pores in the bacterial outer membrane, called Membrane Attack Complexes (MACs). To better understand how these MAC pores damage the complex cell envelope of Gram-negative bacteria, we recently developed a fluorescent reporter system to study membrane damage in E. coli. Here, we used a similar experimental setup in combination with flow cytometry, confocal microscopy and conventional plating assays to elucidate how different components of the immune system act synergistically to effectively clear invading bacteria. We demonstrate how MAC-dependent outer membrane damage enhances the susceptibility of E. coli to further degradation of the cell envelope by lysozyme, leading to drastic changes in the morphology of these bacteria. Furthermore, we elucidate that the MAC enhances the susceptibility of E. coli to phospholipases, and to degradation and killing inside human neutrophils. Altogether, this study provides a detailed overview on how different players of the human immune system work closely together to degrade the complex cell envelope of Gram-negative bacteria. This knowledge may facilitate the development of new antimicrobials that could stimulate, or work synergistically with the immune system.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 29, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes
Dani A. C. Heesterbeek, Remy M. Muts, Vincent P. van Hensbergen, Pieter de Saint Aulaire, Tom Wennekes, Bart W. Bardoel, Nina M. van Sorge, Suzan H.M. Rooijakkers
bioRxiv 2020.01.28.923243; doi: https://doi.org/10.1101/2020.01.28.923243
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes
Dani A. C. Heesterbeek, Remy M. Muts, Vincent P. van Hensbergen, Pieter de Saint Aulaire, Tom Wennekes, Bart W. Bardoel, Nina M. van Sorge, Suzan H.M. Rooijakkers
bioRxiv 2020.01.28.923243; doi: https://doi.org/10.1101/2020.01.28.923243

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3607)
  • Biochemistry (7581)
  • Bioengineering (5529)
  • Bioinformatics (20809)
  • Biophysics (10338)
  • Cancer Biology (7988)
  • Cell Biology (11647)
  • Clinical Trials (138)
  • Developmental Biology (6611)
  • Ecology (10217)
  • Epidemiology (2065)
  • Evolutionary Biology (13630)
  • Genetics (9550)
  • Genomics (12854)
  • Immunology (7925)
  • Microbiology (19555)
  • Molecular Biology (7668)
  • Neuroscience (42147)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2203)
  • Physiology (3269)
  • Plant Biology (7051)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1952)
  • Systems Biology (5429)
  • Zoology (1119)