P128

GangaGen’s lead product is a proprietary recombinant protein, P128, for the topical prevention and treatment of Staphylococcal infections, including infection with methicillin-resistant Staphylococcus aureus (MRSA).

P128 belongs to a new class of antibacterial proteins, called ectolysins.

P128 is a proprietary bacteriophage-derived ectolysin that binds to and kills all Staphylococcus, including drug resistant strains such as methicillin-resistant strains of Staphylococcus aureus (MRSA) and Coagulase Negative Staphylococci (CoNS). It has also been demonstrated to work against these bacteria in biofilms.

How does it work?

P128 has highly specific, receptor mediated; rapid action on all Gram-positive bacteria of the genus Staphylococcus. It acts as an endopeptidase by cleaving the peptide linkages in the Staphylococcal cell wall. The result is rapid degradation of the cell wall, leading to lysis and death of the bacterium within minutes of the binding.

Importantly, this unique mechanism of action allows the P128 protein to kill the bacterium without needing to enter the cell. Therefore, it acts both rapidly and independent of whether the bacterium is in a quiescent (non-active) or active state or as a part of a biofilm.

To date, research has shown that P128 works well on well-known serious disease causing, drug resistant bacteria like MRSA and also on other pathogenic Coagulase Negative Staph like S epidermidis, S. epidermidis, S.lugdunensis. (collectively known as CoNS) which are also commonly associated with serious clinical sequelae including device associated infections in hospitals

P128 Structure

The segment shown in red, CHAP, is the enzymatic domain that degrades the bacterial cell wall.It is the cysteine-histidine aminohydrolase / peptidase (CHAP) domain of open reading frame 56 of Phage K; a portion of the tail-associated muralytic enzyme of the phage.

The segment shown in blue, SH3b, confers staphylococcal binding specificity. This is derived from a bacterial anti-staphylococcal protein, known as lysostaphin. Note that P128 is able to kill bacteria that are resistant to killing by full-length lysostaphin itself.

What it does:

P128 is specific to Staphylococcus and kills rapidly leaving other bacteria untouched. Hence, normal microflora and innocuous inhabitant bacterial population remains unaffected unlike the case with many antibiotics which harm normal indigenous bacterial population also.

The P128 protein has been tested in suitable models in vitro against over 120 strains of S.aureus, more than half of which are methicillin-resistant, and has proved capable of killing all of them, none showing resistance to P128. This panel included 56 Japanese, 8 Canadian, 119 Indian isolates and 30 New Jersey strains representative of more than 2000 isolates from across the globe. This includes efficacy against MRSA, VISA, VRSA and CoNS.