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Viable screening targets related to the bacterial cell wall
Author(s) -
Silver Lynn L.
Publication year - 2013
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12006
Subject(s) - peptidoglycan , bacterial cell structure , antibiotics , cell wall , lipid ii , bacterial protein , bacteria , chemistry , enzyme , biochemistry , computational biology , biology , microbiology and biotechnology , genetics
The synthesis of the bacterial peptidoglycan has been recognized for over 50 years as fertile ground for antibacterial discovery. Initially, empirical screening of natural products for inhibition of bacterial growth detected many chemical classes of antibiotics whose specific mechanisms of action were eventually dissected and defined. Of the nontoxic antibiotics discovered, most were found to be inhibitors of either protein synthesis or cell wall synthesis, which led to more directed screening for inhibitors of these pathways. Directed screening and design programs for cell wall inhibitors have been undertaken since the 1960s. In that time it has become clear that, while certain steps and intermediates have yielded selective inhibitors and are established targets, other potential targets have not yielded inhibitors whose antibacterial activity is proven to be solely due to that inhibition. Why has this search been so problematic? Are the established targets still worth pursuing? This review will attempt to answer these and other questions and evaluate the viability of targets related to peptidoglycan synthesis.