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Updated: Aug 24, 2025
Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
In vitro synergistic action of TAT-RasGAP317-326 peptide with antibiotics against Gram-negative pathogens
Grazia Vizzarro1, Nicolas Jacquier1
1Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
Objectives:
Multidrug-resistant (MDR) bacteria are a continuously increasing threat for medicine, causing infections recalcitrant to antibiotics. Antimicrobial peptides (AMPs) were identified as alternatives to antibiotics, being naturally occurring short peptides and part of the innate immune system of a vast majority of organisms. However, the clinical application of AMPs is limited by suboptimal pharmacokinetic properties and relatively high toxicity. Combinatorial treatments using AMPs and classical antibiotics may decrease the concentrations of AMPs required for bacterial eradication, thus lowering the side effects of these peptides.
Methods:
Here, we investigate the in vitro efficiency of combinations of the recently described antimicrobial peptide TAT-RasGAP317-326 with a panel of commonly used antimicrobial agents against three Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, using checkerboard and time-kill assays.
Results:
We identified synergistic combinations towards all three bacteria and demonstrated that these combinations had an increased bactericidal effect compared to individual drugs. Moreover, combinations were also effective against clinical isolates of A. baumannii. Finally, combination of TAT-RasGAP317-326 and meropenem had a promising antibiofilm effect towards A. baumannii.
Conclusions:
Taken together, our results indicate that combinations of TAT-RasGAP317-326 with commonly used antimicrobial agents may lead to the development of new treatment protocols against infections caused by MDR bacteria.
Insights
Combinations of the antimicrobial peptide TAT-RasGAP317-326 with antibiotics show synergistic effects against multidrug-resistant bacteria. This approach may lead to new treatments for difficult-to-treat infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Multidrug-resistant (MDR) bacteria pose a growing threat to public health, leading to infections that are difficult to treat with current antibiotics.
- Antimicrobial peptides (AMPs) offer potential as alternatives to antibiotics due to their innate immune system origins, but clinical use is hindered by toxicity and poor pharmacokinetics.
- Combining AMPs with conventional antibiotics may reduce required AMP doses, thereby mitigating side effects and enhancing efficacy.
Purpose of the Study:
- To evaluate the in vitro efficacy of combining the antimicrobial peptide TAT-RasGAP317-326 with established antimicrobial agents.
- To assess the synergistic effects of these combinations against Gram-negative bacteria, including common pathogens like Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii.
- To investigate the potential of these combinations in combating antibiotic resistance and biofilm formation.
Main Methods:
- Utilized checkerboard and time-kill assays to determine the in vitro activity of TAT-RasGAP317-326 in combination with various antibiotics.
- Tested the efficacy of identified synergistic combinations against clinical isolates of Acinetobacter baumannii.
- Assessed the antibiofilm potential of the combination of TAT-RasGAP317-326 and meropenem.
Main Results:
- Synergistic antimicrobial activity was observed for TAT-RasGAP317-326 combinations against all three tested Gram-negative bacteria.
- The combined treatments demonstrated enhanced bactericidal effects compared to individual agents.
- Combinations proved effective against clinical isolates of Acinetobacter baumannii, and the TAT-RasGAP317-326 and meropenem combination showed promising antibiofilm activity.
Conclusions:
- Combinations of TAT-RasGAP317-326 with standard antimicrobial agents exhibit significant synergistic effects against MDR Gram-negative bacteria.
- These findings suggest that such combinations could form the basis for novel therapeutic strategies against challenging bacterial infections.
- Further development of these combinatorial approaches may offer a viable solution to the escalating crisis of antibiotic resistance.
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