New Antimicrobials Targeting Bacterial Secretion Being Examined to Fight MRSA

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This new antimicrobial strategy targeting SecA in MRSA may work better than current antibiotics used for treating the infection.
This new antimicrobial strategy targeting SecA in MRSA may work better than current antibiotics used for treating the infection.

A class of antimicrobials that stop part of a bacterium's system could become an important weapon in the battle against methicillin-resistant Staphylococcus aureus (MRSA), according to study published recently in Bioorganic and Medicinal Chemistry.1

Researchers at Georgia State University noted that small analog molecules that attack SecA, a part of the bacterium's secretion system essential to survivability and virulence, can reduce toxin secretion.

Binghe Wang, PhD, Regents' Professor of Chemistry and Phang C. Tai, PhD,  Regents' Professor of Biology and SecA functions expert, both of Georgia State University, noted that this new antimicrobial strategy targeting SecA in MRSA may work better than current antibiotics used for treating the infection.

“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 researchers noted in their report.

According to a prepared statement on the findings, in a previous research, Dr Wang, Dr Tai and colleagues dissected a SecA inhibitor, rose bengal (RB), and developed a new small molecule that was effective in combatting Escherichia coli and Bacillus subtilis.

For this study, “The RB analogs inhibited the ATPase activities of two SecA isoforms identified in S. aureus,” according to the statement. The RB Inhibitor also decreased 3 toxins and prevented 3 MRSA strains from replicating.

In an interview with Infectious Disease Advisor, Dr Wang said that “these inhibitors are very effective against MRSA, [and] their mechanism of action allows these inhibitors intrinsic ability to overcome efflux-mediated drug resistance, which is the underlying reason for multi-drug resistance.  This is a very significant point because there are no easy ways to overcome multi-drug resistance in bacteria.”

Dr Wang and colleagues also created and measured the effectiveness of another potential SecA inhibitor, triazole-pyrimidine analogs, and published the results of this study. The study researchers concluded that SecA inhibitors can be broad-spectrum antimicrobials, stop virulence factor production and disable efflux pumps.2

References

1. Jin J, Cui J, Chaudhary AS et al. Evaluation of small molecule SecA inhibitors against methicillin-resistant Staphylococcus aureus. Bioorg & Med Chem. 2015;23(21):7061-7068.

2. Cui J, Jin J, Chaudhary AS et al. Design, synthesis and evaluation of triazole-pyrimidine analogues as SecA inhibitors. ChemMedChem. doi: 10.1002/cmdc.201500447. Published November 26, 2015. Accessed December 15, 2015.

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