据2月19日的《科学》杂志报道说，有一个部类的抗菌化合物会将假单孢菌的一种必需蛋白质作为标靶并将其摧毁。假单孢菌是一种条件致病菌及一种抗药的细菌，它会给人类健康带来严重的问题。研究人员说，这些抗菌素可能在未来有着重要的治疗上的应用。
Nityakalyani Srinivas及其同僚对抗菌肽protegrin I进行了多次的筛选以寻找抗假单孢菌的活性；他们发现了一种化合物可特异性地抗该种细菌，但却不会作用于其它的格兰氏阴性及阳性细菌。研究人员能够合成一族可模仿这种protegrin肽自然作用的抗菌素，并观察其在小鼠体内抗假单孢菌感染的功效。
研究人员说，他们的抗菌素能够通过摧毁一种叫做LptD的蛋白质（这是其外细胞膜的形成所至关重要的蛋白）而杀灭该致病菌。他们可能在未来在抵抗不同类型的格兰氏阴性菌感染上非常有用，而格兰氏阴性菌与抗多种药物的菌株有关。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
