|
|
|
| A Study on a Novel Biomimetic Antimicrobial Agent |
| ZHAO Biao1, GAO Yang1, ZHOU Hua-feng1,2, DUAN Ming-xing1 |
1. School of Life Sciences, Tsinghua university, State Key Laboratory of Biomembrane and Membrane Biotechnology Beijing 100084, China;
2. Jiangsu longrich Biotechnology Co. Ltd, Jiangsu 215555, China |
|
|
|
Abstract Using biomimetic synthesis technology, we obtained a novel antimicrobial agent α-propargyl-γ-methylene-γ-butyrolactone on the basis of protoanemonin. We characterized bacteriostatic effect and antimicrobial mechanism of the agent using physical and chemical analysis. We carried out the minimum inhibitory concentration (MIC) determination, suspension quantitative germicidal test, and other tests to verify its antimicrobial effect, the mechanism of which were primarily studied through cell wall integrity test and transmission electron microscopy. We found that the novel agent α-propargyl-γ-methylene-γ-butyrolactone had a good inhibitory effect on various bacterial species,especially on Malassezia globosa. Its MIC to malassezia was 0.5mg/ml. Our suspension quantitative germicidal test,using Sodium thiosulfate as neutralizer, showed a high antibacterial efficiency that up to 99.99% of Malassezia globosa is killed after exposed to 10mg/ml agent for only 1min.Membrane integrity experiments and transmission electron experiment suggested that the antimicrobial effect is not due to destroying the cell wall systerm, but it may have some impact on the cell wall.
|
|
Received: 23 April 2013
Published: 25 July 2013
|
|
|
|
|
[1] 魏艳彬,王洪法,抗菌肽的研究进展. 中国现代医生,2009(15):76-78. Wei Y B, Wang H F. The research progress on antimicrobial peptides. China Modern Doctor,2009(15):76-78.
[2] 郑昌戈,王中夏,伍越寰,等.拟原白头翁素的合成与杀菌活性研究. 中国科学技术大学学报, 1999. 29(2): 168-174. Zheng C G, Wang Z X, Wu Y H, et al. A study on synthesis and bactericidal bioactivity of pseudoprotoanemonin. Journal of university of Science and Technology of China,1999.29(2): 168-174.
[3] 伍越环,朱胄远,吴恭谦,等. 原白头翁素生物活性中心的研究. 中国科学技术大学学报, 1991. 21(2): 163-170. Wu Y H,Zhu Z Y,Wu G Q,et al. Study on the bioactivity centre of protoanemonin. Journal of University of Science and Technology of China,1991.21(2): 163-170.
[4] 郭宗儒,天然产物的结构改造. 药学学报,2012,47(2): 144-157. Guo Z R. Modification of natural products for drug discovery. Acta Pharm Sin,2012,47(2): 144-157.
[5] Ashbee H R, Scheynius A. Malassezia, in Pathogenic Yeasts. Springer Berlin Heidelberg, 2010.209.
[6] Gupta A K,kohli Y,Li A,et al. In vitro susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Br J Dermatol, 2000,142(4): 758-765.
[7] 熊心猜,冉玉平,代亚林,等.球形马拉色菌是马拉色菌毛囊炎患者皮损毛囊内的主要菌种. 中华皮肤科杂志, 2004,37(8): 463-465. Xiong X C, Ran Y P,Dai Y L, et al. Malassezia globosa is the main species found in hair follicles of patients with malassezia folliculitis. Chinese journal of Dermatology, 2004,37(8): 463-465.
[8] Chen C Z, Cooper S L. Interactions between dendrimer biocides and bacterial membranes. Biomaterials, 2002,23(16): 3359-3368.
[9] Brogden K A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria. Nat Rev Microbiol, 2005,3(3): 238-250.
[10] Kohanski M A, Dwyer D J,Hayete B,et al. A common mechanism of cellular death induced by bactericidal antibiotics. Cell, 2007, 130(5): 797-810.
[11] 翟培,韩晋辉,侯丽霞,等.家蝇抗菌肽的抑菌动力学研究及其机理初探. 中国生物工程杂志, 2006,26(11):33-39 Zhai P,Han J H,Hou L X,et al, Investigate antibiosis dynamics and antibacterial mechanisms of antibacterial peptides from musca domestica Larvae. China Biotechnology,2006,26(11): 33-39.
[12] Mares D. Antimicrobial activity of protoanemonin, a lactone from ranunculaceous plants. Mycopathologia, 1987,98(3): 133-140.
[13] Faergemann J, Ausma J, Borgers M. In vitro activity of R126638 and ketoconazole against Malassezia species. Acta Derm Venereol, 2006,86(4): 312-315.
[14] Reeder N L, Xu J,Youngquist R S, et al. The antifungal mechanism of action of zinc pyrithione. Br J Dermatol, 2011,165 (2): 9-12.
[15] Holm T,Bruchmann J,Scheynius A, et al. Cell-penetrating peptides as antifungals towards Malassezia sympodialis. Lett Appl Microbiol, 2012, 54(1): 39-44.
[16] Hao G, Shi Y H,Tang Y L,et al., The membrane action mechanism of analogs of the antimicrobial peptide Buforin 2. Peptides, 2009, 30(8): 1421-1427. |
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
