Comparative analysis of the bactericidal activities of amphibian peptide analogues against multidrug-resistant nosocomial bacterial strains
Comparative analysis of the bactericidal activities of amphibian peptide analogues against multidrug-resistant nosocomial bacterial strains
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DOI：
10.1128/aac.00796-07
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发表时间：
2008-01-01
影响因子：
4.9
通讯作者：
Batoni, Giovanna
中科院分区：
文献类型：
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作者：
Mangoni, Maria Luisa;Maisetta, Giuseppantonio;Batoni, Giovanna
由于细菌对现有药物普遍存在耐药性，迫切需要发现新型抗生素，而天然存在的抗菌肽（AMPS）被认为是未来治疗用途的有希望的候选者。两栖动物的皮肤是此类 AMPS 最丰富的来源之一。在本研究中，我们比较了来自三种不同无尾目动物物种的五种 AMPS 对属于经常涉及医院感染的物种（金黄色葡萄球菌、屎肠球菌、铜绿假单胞菌、嗜麦芽寡养单胞菌和鲍曼不动杆菌）的多重耐药临床分离株的体外杀菌活性。测试的肽是来自林蛙的temporins A、B和G； [0101] 来自林蛙的esculentin 1b [Ese(1-18)]的位置1至18的片段；和来自 Bombina variegata 的 bobinin H2。当它们在缓冲液中进行测试时，所有肽在浓度范围为 0.5 至 48 μM 时对所有测试的细菌种类（每个种类 3 个菌株）都有杀菌作用，只有少数例外。研究发现，Temporin 对革兰氏阳性菌具有更强的活性，尤其是在人血清中进行检测时。 Esc(1-18)在2至20分钟内表现出快速而强的杀菌活性，特别是对革兰氏阴性菌，Esc(1-18)在0.5至1μM浓度范围内即可杀死革兰氏阴性菌；铃蟾肽 H2 对所有分离株均表现出相似的杀菌活性。有趣的是，虽然在 20% 人血清存在下，temporins 和 bobinin H2 的活性几乎完全受到抑制，但在 40% 血清存在下，Esc(1-18) 针对革兰氏阴性菌的活性部分保留。这一特性使该肽成为一种有吸引力的分子，可用于开发治疗传染病的新化合物。
Due to the widespread resistance of bacteria to the available drugs, the discovery of new classes of antibiotics is urgently needed, and naturally occurring antimicrobial peptides (AMPS) are considered promising candidates for future therapeutic use. Amphibian skin is one of the richest sources of such AMPS. In the present study we compared the in vitro bactericidal activities of five AMPS from three different species of anurans against multidrug-resistant clinical isolates belonging to species often involved in nosocomial infections (Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii). The peptides tested were temporins A, B, and G from Rana temporaria; the fragment from positions 1 to 18 of esculentin 1b [Ese(1-18)] from Rana esculenta; and bombinin H2 from Bombina variegata. When they were tested in buffer, all the peptides were bactericidal against all bacterial species tested (three strains of each species) at concentrations ranging from 0.5 to 48 mu M, with only a few exceptions. The temporins were found to be more active against gram-positive bacteria, especially when they were assayed in human serum; Esc(1-18) showed fast and strong bactericidal activity, within 2 to 20 min, especially against the gram-negative species, which were killed by Esc(1-18) at concentrations ranging from 0.5 to 1 mu M; bombinin H2 displayed similar bactericidal activity toward all isolates. Interestingly, while the activities of the temporins and bombinin H2 were almost completely inhibited in the presence of 20% human serum, the activity of Esc(1-18) against the gram-negative species was partially preserved in the presence of 40% serum. This property renders this peptide an attractive molecule for use in the development of new compounds for the treatment of infectious diseases.