New drug class may help fight treatment-resistant staph infections
Researchers from Georgia State University in Atlanta have developed a small-molecule analogue drug that appears to both reduce toxin secretion from bacteria and overcome some of the mechanisms of multi-drug resistance seen in bacteria like methicillin-resistant Staphylococcus aureus (MRSA), according to a study published in the journal Bioorganic & Medicinal Chemistry (Nov. 1, 2015; 23(21):7061-7068)
The drug targets the functions of SecA, part of the bacterial secretion system, according to the study. A press release from the university published on Nov. 30, 2015 notes the new molecules may be several times as effective at treating MRSA as the antibiotics currently in use.
“We’ve found that SecA inhibitors are broad-spectrum antimicrobials and are very effective against strains of bacteria that are resistant to existing antibiotics,” study co-leader Binghe Wang, PhD, professor of chemistry at Georgia State, Georgia Research Alliance Eminent Scholar in Drug Discovery and Georgia Cancer Coalition Distinguished Cancer Scholar, said in the release.
The investigating team had previously developed small molecule SecA inhibitors which were effective against Escherichia coli and Bacillus subtillis, by dissecting another SecA inhibitor, Rose Bengal (RB), according to the release. In the study, two of the RB analogues were evaluated against strains of MRSA.
The two RB analogues inhibited certain enzyme activities in some forms of SecA found in S.aureus, reduced the secretion of three S.aureus toxins and stopped three strains of MRSA from reproducing.
In the study, the investigators tested the SecA inhibitors on bacterial strains in which the NorA and MepA efflux pumps – key components of multi-drug resistance in S.aureus – were deleted or over-expressed. Changes in the function of the efflux pumps had a minimal effect on the antimicrobial activities of the SecA inhibitors.