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Updated: Jun 29, 2025
The Application of Open Searching-based Approaches for the Identification of Acinetobacter baumannii O-linked Glycopeptides
Published on: November 2, 2021
Antibacterial activity and mechanism of X33 antimicrobial oligopeptide against Acinetobacter baumannii
Qunlin Lu1,2,3, Xiaoyu Wu1,2,3, Yuan Fang1,2,3
1College of Bioscience and Bioengineering, Jiangxi Agriculture University, Nanchang, 330045, China.
Abstract:
Acinetobacter baumannii is a pathogenic bacterium widespread in human environments, especially in intensive care units, and is associated with high morbidity and infection rates. Multiple drug resistance in A. baumannii frequently leads to the death of patients, making the development of multi-effect antibacterial agents against this bacterium a research hotspot. We have previously found that the X33 antimicrobial oligopeptide can effectively inhibit the growth of Penicillium digitatum and Candida albicans. Herein, we evaluated the antibacterial activity of X33 antimicrobial oligopeptide against A. baumannii by determining the minimum inhibitory concentration, inhibition zone, and growth curve. The increase in extracellular alkaline phosphatase and the leakage of intracellular compounds confirmed the effect of X33 antimicrobial oligopeptide on the cell wall and membrane. Changes in reactive oxygen species, malondialdehyde, ATP, reducing sugar, soluble protein, and pyruvate content demonstrated that the incubation with X33 antimicrobial oligopeptide affected energy metabolism and oxidative stress. Consistent with the physiological characteristics, transcriptomics analysis indicated that incubation with X33 antimicrobial oligopeptide significantly induced changes in the expression of 2339 genes, including 1262 upregulated and 1077 downregulated genes, which participate in oxidative phosphorylation, ribosome, quorum sensing, fatty acid degradation, glycolysis/gluconeogenesis, and citrate cycle pathways. These results provide a fundamental basis for investigating the mechanism of X33 antimicrobial oligopeptide as a potential drug against A. baumannii.
Insights
The X33 antimicrobial oligopeptide shows significant antibacterial activity against Acinetobacter baumannii. This peptide disrupts the bacterial cell wall and membrane, impacting energy metabolism and oxidative stress pathways.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Acinetobacter baumannii is a multidrug-resistant pathogen causing severe infections, particularly in intensive care units.
- Developing novel antibacterial agents against Acinetobacter baumannii is a critical research area due to high mortality rates.
- Previous research demonstrated the efficacy of X33 antimicrobial oligopeptide against fungal pathogens.
Purpose of the Study:
- To evaluate the antibacterial activity of the X33 antimicrobial oligopeptide against Acinetobacter baumannii.
- To investigate the mechanism of action of X33 antimicrobial oligopeptide on Acinetobacter baumannii cells.
- To provide a basis for the development of X33 antimicrobial oligopeptide as a potential therapeutic agent.
Main Methods:
- Minimum inhibitory concentration (MIC), inhibition zone, and growth curve assays were performed.
- Cell wall and membrane integrity were assessed by measuring alkaline phosphatase and intracellular compound leakage.
- Metabolic and oxidative stress markers (ROS, MDA, ATP, etc.) were quantified.
- Transcriptomics analysis was employed to identify gene expression changes.
Main Results:
- X33 antimicrobial oligopeptide demonstrated antibacterial effects against Acinetobacter baumannii.
- The peptide damaged the bacterial cell wall and membrane, leading to the leakage of intracellular components.
- Significant alterations in energy metabolism and oxidative stress pathways were observed.
- Transcriptomics revealed differential expression of genes involved in key metabolic and regulatory pathways.
Conclusions:
- X33 antimicrobial oligopeptide exhibits potent antibacterial activity against Acinetobacter baumannii.
- The mechanism involves disruption of cell integrity and interference with essential metabolic processes.
- These findings support the potential of X33 antimicrobial oligopeptide as a novel therapeutic candidate.
