A novel class of antimicrobials could be effective in fighting methicillin-resistant Staphylococcus aureus (MRSA), one of the major drug-resistant bacterial pathogens, according to a new study.

The new antimicrobials may even be several times more effective than the antibiotics now available for treating the infection, said the researchers at the Georgia State University who conducted the study.

MRSA, caused by a type of Staphylococcus bacteria that has become resistant to many antibiotics used to treat ordinary staph infections, is known to result in serious hospital and community-acquired infections. Healthcare-associated MRSA infections are typically linked to invasive procedures or devices such as surgeries, intravenous tubing or artificial joints.

Community-acquired MRSA, meanwhile, often begins as a skin boil and is spread by skin-to-skin contact. Individuals at risk include competitive wrestlers, child care workers and those living in crowded conditions.

In the study published in the journal Bioorganic & Medicinal Chemistry, the team found that the small molecule analogues that target the functions of SecA have potent antimicrobial activities, reduce the secretion of toxins and can overcome the effect of efflux pumps, which are responsible for multi-drug resistance. SecA is a central part of the general bacterial secretion system required for viability and virulence.

“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 Wang, Regents’ Professor of Chemistry at Georgia State, Georgia Research Alliance Eminent Scholar in Drug Discovery and Georgia Cancer Coalition Distinguished Cancer Scholar.

In a previous study, the researchers developed novel small molecule SecA inhibitors active against the bacteria strains Escherichia coli and Bacillus subtilis by dissecting a SecA inhibitor called Rose Bengal or RB.

For the new study, the team evaluated two potent RB analogues for their activity against MRSA strains. The RB analogues inhibited the ATPase activities of two SecA isoforms identified in S. aureus, SaSecA1 and SaSecA2, as well as the SaSecA1-dependent protein-conducting channel. The inhibitors also reduced the secretion of three toxins from S. aureus and stopped three MRSA strains of bacteria from reproducing.

The best inhibitor in this group, SCA-50, showed strong activity against MRSA Mu50 strain and an inhibitory effect on MRSA Mu50 that was twice to 60 times more potent than all commonly used antibiotics, including vancomycin, the last resort option for treating MRSA-related infections.

In another study recently published online in the journal ChemMedChem, the researchers synthesised and evaluated another new class of triazole-pyrimidine analogues as SecA inhibitors. This study also confirmed that SecA inhibitors have the potential of being broad-spectrum antimicrobials and can directly block virulence factor production and null the effect of efflux pumps.

Because of the widespread resistance of bacteria to antibiotics on the market, there is an urgent need for the development of new antimicrobials such as those included in the study, the team said.

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