Bacterial Type I Signal Peptidases as Antibiotic Targets

Smitha Rao CV; Jozef Anné


Future Microbiol. 2011;6(11):1279-1296. 

In This Article


The SPases are attractive targets as they are essential for life and also play an indirect but important role in maintaining bacterial virulence and related defense mechanisms. The inhibitors that have been identified so far have served as tools for probing the structure and properties of the SPases, facilitated further inhibitor design and enabled target validation. The prospects of exploiting SPases as antibacterial targets remain high, especially given the need for new drugs to combat multidrug resistance and deadly co-infections. One of the challenges ahead is to obtain the 3D-structure of the full-length SPases as this information would not only address basic questions, such as where the cleavage of preproteins takes place (in the membrane or in the aqueous environment), but also reveal what kind of compounds have access to the active site, allowing better inhibitor design. In addition, the structural data on SPases from Gram-positive bacteria would enable comparison and also facilitate the search for potential drugs based on SPases.


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