The methicillin-resistant Staphylococcus aureus (MRSA) bacterium, also known as a "super bug," can cause serious hospital- and community-acquired infections. In a recent development to combat these bacterial pathogens, a team of scientists at Georgia State University says they have found a novel class of antimicrobials that may be several times more effective than current antibiotics used to treat the infection.
The researchers published their new findings in Bioorganic & Medicinal Chemistry at the end of last month, headed by Binghe Wang and Phang Tai, who are both professors at the university.
Central to their findings was the conclusion that targeting a generic part of bacteria called SecA can have strong antimicrobial actions. SecA is important since it is involved in bacterial secretion and crucial for viability and virulence. Efflux pumps are common to bacteria and move compounds such as toxins, neurotransmitters or antibiotics out of the cell. They are responsible for multi-drug resistance in bacteria such as MRSA. The current study shows that targeting SecA also reduces the secretion of toxins and prevents the efflux of antibiotics--bolstering its effect in the highly resistant MRSA.
"We've found that SecA inhibitors are broad-spectrum antimicrobials and are very effective against strains of bacteria that are resistant to existing antibiotics," said Binghe.
Previously, the team had developed small molecules that targeted SecA in Escherichia coli and Bacillus subtilis, with a class of inhibitors called Rose Bengal (RB) showing particular promise.
In the current study, they showed that two potent analogs of RB worked by inhibiting the ATPase activities of a cluster of SecA isoforms. They observed considerable loss in the secretion of toxins from the MRSA bacterium, when treated with the inhibitors.
The most promising small-molecule SecA inhibitor was SCA-50, which was up to 60 times more potent against a particular strain of MRSA, Mu50, than the current treatment of vancomycin used as a last resort in patients in late stages of the infection. In conjunction with a recent publication in ChemMedChem about the development of a new class of triazole-pyrimidine analogs that also target SecA, the benefits of both such findings give hope to the development of a new class of broad-spectrum antimicrobials.