Exciting New Developments in anti-MRSA Drugs

Ever since the deployment of commercially produced Penicillin in 1942, researchers and pharmaceutical companies have been racing to develop more effective, diverse, and broader spectrum antibiotics to treat a variety of bacterial infections. However, interest in antibiotic discovery and development has waned in recent years, in part due to a paradigm shift in pharmaceutical development from curing diseases to treating 'lifestyle' conditions (i.e. Restless Leg Syndrome). While this has been a financially sound decision for shareholders, it has left the human population in danger of encountering microorganisms that have evolved a resistance to most if not all commercially produced antibiotics. A perfect example of this is the prolific MRSA (methicillin resistant Staphylococcus aureus) or MDRSA (Multi-Drug Resistant Staphylococcus aureus), which is the causitive agent of Staph infections and has become a worldwide pandemic. Staph infections result in painful skin wounds that do not heal without treatment and can lead to a lethal septicemia in which the bacteria enter the blood stream and systemically proliferate. MRSA infections have become so dangerous and prolific, the CDC reports that more Americans die of MRSA infections than AIDS each year.

Fortunately, an article published this week in Science, has reported the discovery of a novel antibiotic effective against MRSA ad MDRSA. This new antibiotic, called PC190723, was identified by what the authors describe as 'a fragment based approach' to a process called synthetic chemistry. This involves taking a known molecule that exhibits some modest antibacterial activity and synthetically adding to its structure a variety of chemical moieties. The authors began with a chemical known as 3-Methoxybenzamine (3-MBA), a chemical known to disrupt cell division in the bacterium Bacillus subtilis, and synthetically added two moieties called 'benzamide' and 'thiazolopyridine'. The resulting molecule, known as PC190723, exhibited an antibacterial activity of over 2000 times that of it predacessor, 3-MBA. In fact, PC190723 is capable of inhibiting growth of both MRSA and MDRSA at concentrations as low as 1 microgram per mL (for reference, vancomycin, a commonly used antibiotic for MRSA treatment inhibits bacterial growth at concentrations of 2 micrograms per mL). The authors demonstrate that PC190723 inhibits MRSA (and other bacterial species) cell division by interfering with a protein known as FtsZ, which is required for the bacterium to identify its own cellular midpoint. Without functioning FtsZ, the cellular machinery necessary to drive cell division cannot localize the cell midpoint, effectively preventing the bacteria from dividing (inset photo depicts a MRSA cell dividing at its midpoint).

The most exciting result described in this publication, is that PC190723 offered complete protection to mice infected with a normally lethal dose of Staphylococcus aureus. The authors also demonstrated that PC190723 has no effect on the growth of cultured human cells, further suggesting its potential as a safe and effective anti-bacterial therapy. This molecule is currently in the early stages of clinical trials and hopefully will be available sooner than later to help combat the MRSA pandemic.