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Updated: May 12, 2026

Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and
Daniel B Gilmer1, Jonathan E Schmitz, Chad W Euler
1Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococcus [GrAS]) cause serious and sometimes fatal human diseases. They are among the many Gram-positive pathogens for which resistance to leading antibiotics has emerged. As a result, alternative therapies need to be developed to combat these pathogens. We have identified a novel bacteriophage lysin (PlySs2), derived from a Streptococcus suis phage, with broad lytic activity against MRSA, vancomycin-intermediate S. aureus (VISA), Streptococcus suis, Listeria, Staphylococcus simulans, Staphylococcus epidermidis, Streptococcus equi, Streptococcus agalactiae (group B streptococcus [GBS]), S. pyogenes, Streptococcus sanguinis, group G streptococci (GGS), group E streptococci (GES), and Streptococcus pneumoniae. PlySs2 has an N-terminal cysteine-histidine aminopeptidase (CHAP) catalytic domain and a C-terminal SH3b binding domain. It is stable at 50 °C for 30 min, 37 °C for >24 h, 4°C for 15 days, and -80 °C for >7 months; it maintained full activity after 10 freeze-thaw cycles. PlySs2 at 128 μg/ml in vitro reduced MRSA and S. pyogenes growth by 5 logs and 3 logs within 1 h, respectively, and exhibited a MIC of 16 μg/ml for MRSA. A single, 2-mg dose of PlySs2 protected 92% (22/24) of the mice in a bacteremia model of mixed MRSA and S. pyogenes infection. Serially increasing exposure of MRSA and S. pyogenes to PlySs2 or mupirocin resulted in no observed resistance to PlySs2 and resistance to mupirocin. To date, no other lysin has shown such notable broad lytic activity, stability, and efficacy against multiple, leading, human bacterial pathogens; as such, PlySs2 has all the characteristics to be an effective therapeutic.
Insights
A novel bacteriophage lysin, PlySs2, demonstrates broad-spectrum activity against dangerous Gram-positive pathogens like MRSA and Streptococcus pyogenes. This stable and effective therapeutic shows promise in combating antibiotic resistance.
Area of Science:
- Microbiology
- Biochemistry
- Therapeutics
Background:
- Antibiotic resistance in Gram-positive pathogens like Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A Streptococcus [GrAS]) necessitates novel therapeutic strategies.
- The emergence of resistance to existing antibiotics poses a significant threat to public health, driving the search for alternative treatments.
Purpose of the Study:
- To identify and characterize a novel bacteriophage lysin with broad lytic activity against clinically significant Gram-positive bacteria.
- To evaluate the stability, efficacy, and resistance potential of the identified lysin, PlySs2, as a potential therapeutic agent.
Main Methods:
- Identification and purification of the bacteriophage lysin PlySs2 from Streptococcus suis.
- Assessment of PlySs2's lytic activity spectrum against various Gram-positive pathogens, including MRSA and S. pyogenes.
- Evaluation of PlySs2's stability under different temperature and storage conditions.
- In vitro and in vivo efficacy studies using bacteremia models and MIC determination.
- Analysis of resistance development to PlySs2 compared to mupirocin.
Main Results:
- PlySs2 exhibited broad lytic activity against a wide range of Gram-positive bacteria, including MRSA, vancomycin-intermediate S. aureus (VISA), S. pyogenes, and Listeria species.
- The lysin demonstrated remarkable stability at various temperatures and after multiple freeze-thaw cycles.
- In vitro, PlySs2 significantly reduced MRSA and S. pyogenes growth and showed a low minimum inhibitory concentration (MIC) for MRSA.
- A single dose of PlySs2 provided significant protection in a murine bacteremia model.
- No resistance developed to PlySs2 upon serial exposure, unlike mupirocin.
Conclusions:
- PlySs2 is a potent, stable, and broad-spectrum bacteriophage lysin with significant therapeutic potential against critical Gram-positive pathogens.
- Its ability to overcome existing resistance mechanisms and lack of induced resistance make PlySs2 a promising candidate for novel antibiotic therapies.
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