Dataset Information

Antimicrobial peptide A20L: in vitro and in vivo antibacterial and antibiofilm activity against carbapenem-resistant Klebsiella pneumoniae.

ABSTRACT: Antimicrobial resistance has become a growing public health threat in recent years. Klebsiella pneumoniae is one of the priority pathogens listed by the World Health Organization. Antimicrobial peptides are considered promising alternatives to antibiotics due to their broad-spectrum antibacterial activity and low resistance. In this study, we investigated the antibacterial activity of antimicrobial peptide A20L against K. pneumoniae. In vitro antibacterial activity of A20L against K. pneumoniae was demonstrated by broth microdilution method. We confirmed the in vivo efficacy of A20L by Galleria mellonella infection model. In addition, we found that A20L also had certain antibiofilm activity by crystal violet staining. We also evaluated the safety and stability of A20L, and the results revealed that at a concentration of ≤128 µg/mL, A20L exhibited negligible toxicity to RAW264.7 cells and no substantial toxicity to G. mellonella. A20L was stable at different temperatures and with low concentration of serum [5% fetal bovine serum (FBS)]; however, Ca²⁺, Mg²⁺, and high serum concentrations reduced the antibacterial activity of A20L. Scanning electron microscope (SEM) and membrane permeability tests revealed that A20L may exhibit antibacterial action by damaging bacterial cell membranes and increasing the permeability of outer membrane. Taken together, our results suggest that A20L has significant development potential as a therapeutic antibiotic alternative, which provides ideas for the treatment of K. pneumoniae infection.

Importance

A20L showed antibacterial and anti-infective efficacy in vitro and in vivo against Klebsiella pneumoniae. It can have an antibacterial effect by disrupting the integrity of cell membranes. A20L displayed anti-biofilm and anti-inflammatory activity against carbapenem-resistant K. pneumoniae and certain application potential in vivo, which provides a new idea for the clinical treatment of biofilm-associated infections.

SUBMITTER: Zhou H

PROVIDER: S-EPMC11302274 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Antimicrobial peptide A20L: in vitro and in vivo antibacterial and antibiofilm activity against carbapenem-resistant Klebsiella pneumoniae.

Zhou Huijing H Du Xin X Wang Yue Y Kong Jingchun J Zhang Xiaodong X Wang Weixiang W Sun Yao Y Zhou Cui C Zhou Tieli T Ye Jianzhong J

Microbiology spectrum 20240709 8

Antimicrobial resistance has become a growing public health threat in recent years. Klebsiella pneumoniae is one of the priority pathogens listed by the World Health Organization. Antimicrobial peptides are considered promising alternatives to antibiotics due to their broad-spectrum antibacterial activity and low resistance. In this study, we investigated the antibacterial activity of antimicrobial peptide A20L against K. pneumoniae. In vitro antibacterial activity of A20L against ...[more]

PMID: 38980018

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Project description:To fight the global epidemic of drug-resistant bacteria, essential oils have gained increasing attention as a new source of antibiotics. The antimicrobial activity of Monarda didyma essential oils (MDEO) for the Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were determined by agar disc diffusion assay and broth microdilution assay. To further understand MDEO efficacy, a time-growth curve was performed. The biofilm formation of CRKP were determined by crystalline violet staining method, additionally, changes in intracellular Adenosine triphosphate (ATP), protein, Alkaline phosphatase (AKP) activities, and membrane integrity were investigated to assess the influence of MDEO on cell membrane damage. Finally, the activities of key enzymes in the tricarboxylic acid (TCA) pathways and pentose phosphate (PPP) pathways were examined to determine the effect of MDEO on the respiratory metabolism of CRKP. This study presents the antibacterial mechanism of MDEO against CRKP with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1.25 mg/ml. To understand MDEO efficacy, a time-kill kinetics approach was performed. The bactericidal effect of MDEO was evident at 2 h compared to the control at its MIC and 2MIC. Surface electron microscopic and ATP assay studies provided evidence for the multi-target action of MDEO against CRKP. MDEO could inhibit CRKP biofilm formation. MDEO could also cause irreversible damage to the CRKP cell membrane, resulting in the leakage of biological macromolecules (protein, ATP) and the reduction of intracellular enzymes (AKP) activities. Finally, MDEO affected the pathways of respiratory metabolism, such as PPP and TCA pathways. MDEO could reduce the activity of key enzymes (Glucose-6-phosphate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase) in the PPP and TCA pathways to exert its biological effects against CRKP. These results suggest MDEO can exert inhibitory effects on CRKP, and potential mechanisms of action including inhibition of biofilm formation, damage of cell membrane structure and inhibition of energy metabolism.

Dataset Information

Antimicrobial peptide A20L: in vitro and in vivo antibacterial and antibiofilm activity against carbapenem-resistant Klebsiella pneumoniae.

Importance

Publications

Antimicrobial peptide A20L: <i>in vitro</i> and <i>in vivo</i> antibacterial and antibiofilm activity against carbapenem-resistant <i>Klebsiella pneumoniae</i>.

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