Complement-dependent outer membrane perturbation sensitizes Gram-negative bacteria to Gram-positive specific
D A C Heesterbeek1, N I Martin2, A Velthuizen1
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Scientific Reports
|March 1, 2019
Summary
The complement system
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Gram-negative bacteria possess an outer membrane hindering antibiotic penetration.
- The complement system's Membrane Attack Complex (MAC) targets bacterial membranes.
Purpose of the Study:
- To investigate the kinetics of MAC-induced damage in Gram-negative bacteria.
- To determine if MAC-induced damage can sensitize bacteria to antibiotics typically ineffective against them.
Main Methods:
- Assessing outer and inner membrane damage kinetics after MAC attack.
- Testing synergy between serum complement and Gram-positive-specific antibiotics (e.g., nisin, vancomycin) against Gram-negative bacteria.
- Evaluating sensitization in clinical isolates and a multi-drug resistant (MDR) Klebsiella pneumoniae strain.
Main Results:
- MAC rapidly damages the outer membrane but slowly damages the inner membrane.
- MAC-induced outer membrane damage sensitizes Gram-negative bacteria to Gram-positive antibiotics.
- Synergistic effects observed with serum and nisin in 22/53 isolates and MDR strains.
- Blood sensitized MDR K. pneumoniae to vancomycin, demonstrating in vivo relevance.
Conclusions:
- Complement-mediated outer membrane damage is a key step in bacterial killing.
- This damage can restore efficacy to antibiotics previously ineffective against Gram-negative bacteria.
- The complement system's presence may alter antibiotic treatment outcomes for Gram-negative infections.
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