據(jù)2月19日的《科學(xué)》雜志報道說,，有一個部類的抗菌化合物會將假單孢菌的一種必需蛋白質(zhì)作為標(biāo)靶并將其摧毀。假單孢菌是一種條件致病菌及一種抗藥的細(xì)菌,，它會給人類健康帶來嚴(yán)重的問題,。研究人員說，這些抗菌素可能在未來有著重要的治療上的應(yīng)用,。
Nityakalyani Srinivas及其同僚對抗菌肽protegrin I進(jìn)行了多次的篩選以尋找抗假單孢菌的活性,；他們發(fā)現(xiàn)了一種化合物可特異性地抗該種細(xì)菌，但卻不會作用于其它的格蘭氏陰性及陽性細(xì)菌,。研究人員能夠合成一族可模仿這種protegrin肽自然作用的抗菌素,，并觀察其在小鼠體內(nèi)抗假單孢菌感染的功效,。
研究人員說，他們的抗菌素能夠通過摧毀一種叫做LptD的蛋白質(zhì)（這是其外細(xì)胞膜的形成所至關(guān)重要的蛋白）而殺滅該致病菌,。他們可能在未來在抵抗不同類型的格蘭氏陰性菌感染上非常有用,，而格蘭氏陰性菌與抗多種藥物的菌株有關(guān)。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 19 February 2010: DOI: 10.1126/science.1182749
Peptidomimetic Antibiotics Target Outer-Membrane Biogenesis in Pseudomonas aeruginosa
Nityakalyani Srinivas,1 Peter Jetter,1 Bernhard J. Ueberbacher,1 Martina Werneburg,1 Katja Zerbe,1 Jessica Steinmann,1 Benjamin Van der Meijden,1 Francesca Bernardini,2 Alexander Lederer,2 Ricardo L. A. Dias,2 Pauline E. Misson,2 Heiko Henze,2 Jürg Zumbrunn,2 Frank O. Gombert,2 Daniel Obrecht,2 Peter Hunziker,3 Stefan Schauer,3 Urs Ziegler,4 Andres K?ch,4 Leo Eberl,5 Kathrin Riedel,5 Steven J. DeMarco,2,* John A. Robinson1,*
Antibiotics with new mechanisms of action are urgently required to combat the growing health threat posed by resistant pathogenic microorganisms. We synthesized a family of peptidomimetic antibiotics based on the antimicrobial peptide protegrin I. Several rounds of optimization gave a lead compound that was active in the nanomolar range against Gram-negative Pseudomonas spp., but was largely inactive against other Gram-negative and Gram-positive bacteria. Biochemical and genetic studies showed that the peptidomimetics had a non–membrane-lytic mechanism of action and identified a homolog of the β-barrel protein LptD (Imp/OstA), which functions in outer-membrane biogenesis, as a cellular target. The peptidomimetic showed potent antimicrobial activity in a mouse septicemia infection model. Drug-resistant strains of Pseudomonas are a serious health problem, so this family of antibiotics may have important therapeutic applications.
1 Chemistry Department, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
2 Polyphor AG, Hegenheimermattweg 125, 4123 Allschwil, Switzerland.
3 Functional Genomics Center Zürich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
4 Center for Microscopy and Image Analysis, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
5 Department of Microbiology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich.
