SecA inhibitors show in vitro efficacy against MRSA




A promising approach to treating methicillin-resistant Staphylococcus aureus (MRSA) infections may lie in small molecules that target SecA, an indispensable ATPase of the general protein translocation machinery present in bacteria, according to Jinshan Jin, Ph.D.

Dr. Jin and his coinvestigators at Georgia State University developed small molecule analogs of Rose Bengal that target SecA. In in vitro studies, the analogs had potent antimicrobial activities, reduced the secretion of toxins, and overcame the effect of efflux pumps, which are responsible for multi-drug resistance. The ability to inhibit virulence factor secretion is something most currently available and commonly prescribed antibiotics are unable to do, making small molecule treatments an attractive option if such treatments are proven effective in vivo. The small molecule inhibitors reduced the secretion of three toxins from S. aureus and exerted potent bacteriostatic effects against three MRSA strains, the researchers reported (Bioorganic & Medicinal Chemistry Vol. 23; 2015, 7061–68). “Our best inhibitor SCA-50 showed potent concentration-dependent bactericidal activity against MRSA Mu50 strain and very importantly, 2–60 fold more potent inhibitory effect on MRSA Mu50 than all the commonly used antibiotics including vancomycin, which is considered the last resort option in treating MRSA-related infections.”

“The results obtained demonstrated an important proof of concept [that] targeting SecA could achieve antimicrobial effect through three mechanisms, which are not seen with any single class of antimicrobial agents,” Dr. Jin and his coauthors wrote.

This study was funded by the National Institutes of Health and by Georgia State University. Dr. Jin is now with the National Center of Toxicological Research, in Jefferson, Ariz.

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