局所細菌感染症の治療として、セラゲニンCSA-13とプルロニックF-127との混合物の可能性

目的：セラゲニンCSA-13は、カチオン性抗菌ペプチドの合成模倣物であり、胆嚢酸足場を使用して顔面両親媒性の形態が再現されています。Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma.However, at higher concentrations, CSA-13 can cause lysis of erythrocytes.This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. 方法と結果：局所感染症に関連する細菌の臨床的株に対するCSA-13細菌活性および、嚢胞性線維症（CF）に苦しむ患者のさまざまな上皮組織液や気道の吐き気など、病態生理学的環境に関連する実験的環境（CF）がありました。evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killingアッセイ。プルロニックF-127の存在下では、CSA-13抗菌活性はわずかに減少しただけであるが、CSA-13溶血活性が有意に阻害されることがわかった。CSA-13は、メチシリン耐性株、CF sputaに存在するシュードモナス緑膿菌、異なるグラム（+）およびグラム（ - ）細菌によって形成されたバイオフィルムを含む黄色ブドウ球菌の臨床分離株に対する細菌殺害活性を示します。CSA-13細菌作用は、血漿の存在下で部分的に損なわれますが、腹水、脳脊髄液、唾液、気管支肺胞洗浄液で維持されます。標準的なチェッカーボードアッセイの使用によって決定されるCSA-13の相乗作用は、カテリシジンLL-37ペプチド、リゾチーム、ラクトフェリン、および分泌ホスホリピースAなどの宿主防御分子の存在下でのCSA-13抗菌活性の増加を明らかにしています。(sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.

AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.