Combating Antibiotic Resistance: PlySs2's Potency in Neutralizing MRSA and S. pyogenes Infections

Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococcus [GAS]) are significant causes of severe and potentially fatal diseases. The rise of antibiotic resistance among these Gram-positive bacteria necessitates the development of new treatment strategies. A newly identified bacteriophage lysin, PlySs2, derived from a Streptococcus suis phage, has demonstrated broad-spectrum lytic activity against MRSA, VISA, and a range of other Gram-positive bacteria, including various Streptococcus and Listeria species.

PlySs2 is composed of an N-terminal CHAP catalytic domain and a C-terminal SH3b binding domain. It has shown remarkable stability at various temperatures and retained full activity even after multiple freeze-thaw cycles. In vitro, PlySs2 significantly reduced the growth of MRSA and S. pyogenes within an hour and exhibited a low MIC value for MRSA. In a mouse bacteremia model, a single dose of PlySs2 provided substantial protection against a mixed infection of MRSA and S. pyogenes. Notably, there was no observed resistance development to PlySs2 after serial exposure, unlike the resistance observed to mupirocin.

The lysin's broad lytic activity, combined with its stability and efficacy, suggests that PlySs2 has the potential to be an effective therapeutic agent against multiple prominent human bacterial pathogens, including those that have developed resistance to standard antibiotics.