New Antibiotic Class Proves Effective Against MRSA

A new class of antibacterial compounds involving broad spectrum antibacterial proteins (SASPs) act by binding to bacterial DNA and halting replication and gene expression, resulting in rapid cell death.

The new technology, called SASPject, combines SASPs with a delivery vector that can be programmed to target selected bacteria. The technology can be used against all bacteria, including those that are multiple antibiotic resistant, such as methicillin resistant Staphylococcus aureus (MRSA), with the advantage that it can be targeted to individual or multiple bacterial species. The opportunity for resistance to SASPject to develop is severely limited with the active ingredient SASP, which targets and inactivates a fundamental and crucial bacterial cell component – DNA. The SASPject can inactivate antibiotic resistance genes, a feature not currently available from any conventional antibiotic. In the presence of SASP, bacteria cannot replicate, protein production is halted preventing an increase in the levels of toxins and antibiotic resistance determinants, and most importantly, the targeted bacteria cannot survive.

When the bacteria stop producing toxins and stop dividing, the spread of infection is halted and the immune system has time to remove the bacteria from the body. Although the gross effect of SASP is to inactivate chosen bacteria, its use has important additional benefits, since SASP can bind to and inactivate all the DNA inside the bacteria, including plasmid DNA, which is a common source of antibiotic resistance genes. SASP can therefore actively help to prevent the spread of antibiotic resistance and toxin genes.
The delivery vector utilizes fully characterized bacterial viruses (bacteriophages) as the starting point and modifies and simplifies these so that they retain only the required characteristics, thus targeting only bacterial cells and no other cell type. The delivery vector therefore acts as a syringe, injecting the SASP gene into bacterial cells where SASP causes inhibition of bacterial cell function with concomitant irreversible loss of viability. PT1.2, the lead compound in the SASP group, is being developed by researchers at Phico Therapeutics (Cambridge, United Kingdom).

"SASP was rapidly bactericidal against all 10 different MRSA isolates gathered from across the US,” said Dr. Heather Fairhead, CEO of Phico Therapeutics. "Indeed in the speed of kill assay, SASP caused a >99.9 % drop in viability within 2 minutes against the 10^5 culture and a >99.9 % drop in viability within 10 minutes against the 10^7 culture. This data gives us the confidence to take PT1.2 into the clinic.”

According to the company, proof of principle of the SASP platform technology has been established in the Gram-positive bacterium, Staphylococcus aureus (including MRSA) and the Gram-negative bacterium, Escherichia coli.


Related Links:
Phico Therapeutics