Abstract
Acinetobacter baumannii is a serious nosocomial pathogen with multiple drug resistance (MDR), the control of which has become challenging due to the currently used antibiotics. Our main objective in this study is to determine the antibacterial and antibiofilm activities of the antimicrobial peptide, Octominin, against MDR A. baumannii and derive its possible modes of actions. Octominin showed significant bactericidal effects at a low minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of 5 and 10 µg/mL, respectively. Time-kill kinetic analysis and bacterial viability tests revealed that Octominin showed a concentration-dependent antibacterial activity. Field-emission scanning electron microscopy (FE-SEM) analysis revealed that Octominin treatment altered the morphology and membrane structure of A. baumannii. Propidium iodide (PI) and reactive oxygen species (ROS) generation assays showed that Octominin increased the membrane permeability and ROS generation in A. baumannii, thereby causing bacterial cell death. Further, a lipopolysaccharides (LPS) binding assay showed an Octominin concentration-dependent LPS neutralization ability. Biofilm formation inhibition and eradication assays further revealed that Octominin inhibited biofilm formation and showed a high biofilm eradication activity against A. baumannii. Furthermore, up to a concentration of 100 µg/mL, Octominin caused no hemolysis and cell viability changes in mammalian cells. An in vivo study in zebrafish showed that the Octominin-treated group had a significantly higher relative percentage survival (54.1%) than the untreated group (16.6%). Additionally, a reduced bacterial load and fewer alterations in histological analysis confirmed the successful control of A. baumannii by Octominin in vivo. Collectively, these data suggest that Octominin exhibits significant antibacterial and antibiofilm activities against the multidrug-resistant A. baumannii, and this AMP can be developed further as a potent AMP for the control of antibiotic resistance.
Highlights
Acinetobacter baumannii is a Gram-negative, non-motile, strictly aerobic, non-fermenting coccobacillus and is considered a part of the Acinetobacter complex (ABC) consisting of A.baumannii, A. calcoaceticus, and genomic species 13TU [1,2]
Our results showed that Octominin exhibited growth inhibition and bactericidal activities against A. baumannii at low concentrations (MIC, 5 μg/mL; minimum bactericidal concentration (MBC), 10 μg/mL), with an MBC/minimum inhibitory concentration (MIC) ratio of 2.0
Level, which was similar to the chloramphenicol activity at the same concentration. These results suggest that Octominin has a strong antibiofilm activity against multiple drug resistance (MDR) A. baumannii isolates, which may be due to the penetration of Octominin via the biofilm matrix
Summary
Acinetobacter baumannii is a Gram-negative, non-motile, strictly aerobic, non-fermenting coccobacillus and is considered a part of the Acinetobacter complex (ABC) consisting of A.baumannii, A. calcoaceticus, and genomic species 13TU [1,2]. A. baumannii is highly contagious and can cause multiple infections in the human lungs, blood, brain, urinary tract, and skin, leading to multiple complications, such as pneumonia, meningitis, septicemia, urinary tract infections, and abscesses [3]. It can be transmitted via direct contact or contaminated water, food, and even soil. A. baumannii is considered to be a member of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), a high-risk infectious pathogen group mainly responsible for hospital-based infections [7,8]. Finding an efficient and commercially available antibiotic has become challenging [9]; there is an urgent need to develop novel therapeutic drug candidates against ESKAPE species
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