Protegrin-1: A broad-spectrum, rapidly microbicidal peptide with in vivo activity
Protegrin-1: A broad-spectrum, rapidly microbicidal peptide with in vivo activity
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DOI：
10.1128/aac.41.8.1738
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发表时间：
1997-08-01
影响因子：
4.9
通讯作者：
Fiddes, JC
中科院分区：
文献类型：
--
作者：
Steinberg, DA;Hurst, MA;Fiddes, JC
Protegrin-1（PG-1）是一种富含半胱氨酸的18个残基的β折叠肽，从猪白细胞中分离得到，具有抗多种微生物的抗微生物活性。PG-I对代表性革兰氏阳性和革兰氏阴性细菌的MIC范围为0.12至2 μ g/ml。在这些水平下，PG-I在体外快速杀菌，在不到15分钟内减少耐甲氧西林金黄色葡萄球菌（MRSA）或铜绿假单胞菌的活CFU数超过3个对数单位。对PG-I的耐药性在铜绿假单胞菌或MRSA的15次传代培养11次后没有发展。在含有PG-1的Mueller-Hinton肉汤中以MIC的一半。在相似的连续传代条件下，诺氟沙星和庆大霉素对铜绿假单胞菌的MIC分别提高了10倍和190倍。同样，诺氟沙星对MRSA的MIC增加了85倍。免疫活性小鼠腹腔内（i.p）接种铜绿假单胞菌或金黄色葡萄球菌后，溶媒对照组的死亡率为93 - 100%，而单次i. p注射PG-1（0.5 mg/kg体重）的动物死亡率为0 - 27%。通过静脉内（i，v）注射接种沙门氏菌并在0至60分钟后单次静脉内注射PG-1（5 mg/kg）的小鼠的死亡率为7至33%，而载体对照的死亡率为73至93%。在i，v接种万古霉素抗性屎肠球菌的白细胞减少小鼠中，媒介物对照组的死亡率为87%，而接受单次i、v注射PG-1（2.5 mg/kg）的动物的死亡率为33%。总之，这些数据表明PG-1有可能用作治疗由临床相关病原体引起的局部或全身感染的抗菌剂。
Protegrin-1 (PG-1) is a cysteine-rich, 18-residue beta-sheet peptide isolated from porcine leukocytes with antimicrobial activity against a broad range of microorganisms. The MICs of PG-I against representative gram-positive and gram-negative bacteria ranged from 0.12 to 2 mu g/ml. At these levels, PG-I was rapidly bactericidal in vitro, reducing the number of viable CFU of either methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa by more than three log units in less than 15 min. Resistance to PG-I did not develop after 11 subculturings of P, aeruginosa or 15 subcultures of MRSA. in Mueller-Hinton broth containing PG-1 at one-half the MIC. Under similar conditions of serial passage, the MICs of norfloxacin and gentamicin against P, aeruginosa increased 10 and 190 times, respectively. Similarly, the MIC of norfloxacin against MRSA increased 85 times. Immunocompetent mice inoculated intraperitoneally (i.p,) with P. aeruginosa or S, aureus exhibited 93 to 100% mortality in the vehicle control group compared with 0 to 27% mortality in animals that received a single i,p, injection of PG-I (0.5 mg/kg of body weight). Mice inoculated with S, aar ens by intravenous (i,v,) injection and dosed 0 to 60 min later with a single i.v, injection of PG-1 (5 mg/kg) had a mortality of 7 to 33%, compared to a mortality of 73 to 93% ire the vehicle controls, In leukopenic mice inoculated i,v, with vancomycin-resistant Enterococcus faecium, mortality was 87% in the vehicle control group and 33% in animals that received a single i,v, injection of PG-I (2.5 mg/kg). Taken together, these data indicate that PG-1 has potential for use as an antimicrobial agent in the treatment of local or systemic infections caused by clinically relevant pathogens.