BACKGROUND Treatment of P. aeruginosa wound infection is challenging due to its inherent and acquired resistance to many conventional antibiotics. Cationic antimicrobial peptides (CAMPs) with distinct modes of antimicrobial action have been considered as the next-generation therapeutic agents. In the present study, a murine skin surgical wound infection model was used to evaluate the in vivo toxicity and efficacy of two newly designed antimicrobial peptides (CAMP-A and CAMP-B), as chemotherapeutic agents to combat P. aeruginosa infection. RESULTS In the first trial, topical application of CAMPs on the wounds at a dose equivalent to 4 × MIC for 7 consecutive days did not cause any significant changes in the physical activities, hematologic and plasma biochemical parameters, or histology of systemic organs of the treated mice. Daily treatment of infected wounds with CAMP-A and CAMP-B for 5 days at a dose equivalent to 2× MIC resulted in a significant reduction in wound bacterial burden (CAMP-A: 4.3 log10CFU/g of tissue and CAMP-B: 5.8 log10CFU/g of tissue), compared to that of the mock-treated group (8.1 log10CFU/g of tissue). Treatment with CAMPs significantly promoted wound closure and induced epidermal cell proliferation. Topical application of CAMP-A on wounds completely prevented systemic dissemination of P. aeruginosa while CAMP-B blocked systemic infection in 67% of mice and delayed the onset of systemic infection by at least 2 days in the rest of the mice (33%). In a second trial, daily application of CAMP-A at higher doses (5× MIC and 50× MIC) didn't show any significant toxic effect on mice and the treatments with CAMP-A further reduced wound bacterial burden (5× MIC: 4.5 log10CFU/g of tissue and 50× MIC: 3.8 log10CFU/g of tissue). CONCLUSIONS The data collectively indicated that CAMPs significantly reduced wound bacterial load, promoted wound healing, and prevented hepatic dissemination. CAMP-A is a promising alternative to commonly used antibiotics to treat P. aeruginosa skin infection.

中文翻译：

---

在鼠皮肤伤口感染模型中，新型CAMP对铜绿假单胞菌感染的抗菌功效和毒性。

背景技术铜绿假单胞菌伤口感染的治疗由于其对许多常规抗生素的固有和获得的抗性而具有挑战性。具有不同抗菌作用模式的阳离子抗菌肽（CAMP）已被视为下一代治疗剂。在本研究中，鼠皮肤外科手术伤口感染模型用于评估两种新设计的抗菌肽（CAMP-A和CAMP-B）作为对抗铜绿假单胞菌感染的化学治疗剂的体内毒性和功效。结果在第一个试验中，连续7天以相当于4×MIC的剂量在伤口上局部应用CAMPs不会导致被治疗者的身体活动，血液和血浆生化参数或全身器官的组织学发生任何显着变化老鼠。用CAMP-A和CAMP-B以相当于2倍MIC的剂量每天治疗感染的伤口5天，可显着减少伤口细菌负担（CAMP-A：4.3 log10CFU / g组织和CAMP-B：5.8与模拟治疗组（8.1 log10CFU / g组织）相比，log10CFU / g组织）。用CAMPs治疗显着促进伤口闭合并诱导表皮细胞增殖。在伤口上局部使用CAMP-A可以完全阻止铜绿假单胞菌的全身性传播，而CAMP-B可以阻止67％的小鼠发生全身性感染，并且在其余小鼠（33％）中将全身性感染的发生延迟至少2天。 。在第二项试验中，每天以较高剂量（5倍MIC和50倍MIC）施用CAMP-A并没有' t对小鼠没有任何明显的毒性作用，CAMP-A处理可进一步减轻伤口细菌负担（5x MIC：4.5 log10CFU / g组织和50x MIC：3.8 log10CFU / g组织）。结论数据共同表明，CAMPs显着降低了伤口细菌负荷，促进了伤口愈合，并阻止了肝的扩散。CAMP-A是治疗铜绿假单胞菌皮肤感染的常用抗生素的有前途的替代品。