TY - JOUR
T1 - Synergistic efficacy of Aedes aegypti antimicrobial peptide cecropin A2 and tetracycline against Pseudomonas aeruginosa
AU - Zheng, Zhaojun
AU - Tharmalingam, Nagendran
AU - Liu, Qingzhong
AU - Jayamani, Elamparithi
AU - Kim, Wooseong
AU - Fuchs, Beth Burgwyn
AU - Zhang, Rijun
AU - Vilcinskas, Andreas
AU - Mylonakis, Eleftherios
N1 - Funding Information:
This study was supported by the China Scholarship Council (CSC) through the Chinese Government Graduate Student Overseas Study Program to Z.Z. and by the National Institutes of Health (grant P01 AI083214 to E.M.). A.V. acknowledges funding by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK) via the LOEWE Center for Insect Biotechnology and Bioresources.
Publisher Copyright:
Copyright © 2017 American Society for Microbiology. All Rights Reserved.
PY - 2017/7
Y1 - 2017/7
N2 - The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrugresistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36- residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pathogen Pseudomonas aeruginosa. The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical P. aeruginosa isolates were 32 to 64 μg/ml, and its MICs versus other Gramnegative bacteria were 2 to 32 μg/ml. Importantly, cecropin A2 demonstrated synergistic activity against P. aeruginosa when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective in vivo in the P. aeruginosa/Galleria mellonella model (P < 0.001). We found that cecropin A2 bound to P. aeruginosa lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against P. aeruginosa in vitro and in vivo, offering an alternative approach for the treatment of P. aeruginosa infections.
AB - The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrugresistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36- residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pathogen Pseudomonas aeruginosa. The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical P. aeruginosa isolates were 32 to 64 μg/ml, and its MICs versus other Gramnegative bacteria were 2 to 32 μg/ml. Importantly, cecropin A2 demonstrated synergistic activity against P. aeruginosa when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective in vivo in the P. aeruginosa/Galleria mellonella model (P < 0.001). We found that cecropin A2 bound to P. aeruginosa lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against P. aeruginosa in vitro and in vivo, offering an alternative approach for the treatment of P. aeruginosa infections.
KW - Antimicrobial activity
KW - Antimicrobial peptide
KW - Cecropin A2
KW - Pseudomonas aeruginosa
KW - Tetracycline
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U2 - 10.1128/AAC.00686-17
DO - 10.1128/AAC.00686-17
M3 - Article
C2 - 28483966
AN - SCOPUS:85021913413
SN - 0066-4804
VL - 61
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 7
M1 - e00686-17
ER -