New Publication in Antimicrobial Agents and Chemotherapy: LYSG101 Clears MRSA in Animal Models with No Detectable Resistance

A new peer-reviewed study in Antimicrobial Agents and Chemotherapy, named an Editor's Pick by the journal, reports that LYSG101 (also called ClyO), an engineered lysin developed by Precisio Biotix against Staphylococcus aureus, improved survival in animal models of infection, killed clinical isolates within minutes, cleared established biofilms, and did not select for resistance after 100 rounds of passage. Its potency was roughly ten times that of exebacase, the lysin furthest along in clinical testing for staphylococcal disease.

Lysins are enzymes that break open the bacterial cell wall. Because LYSG101 attacks a structural part of the cell rather than a metabolic pathway, it kills quickly and gives bacteria little chance to adapt, unlike most conventional antibiotics.

The animal results at the heart of the study show that a single dose of LYSG101 significantly improved survival in two lethal mouse models of S. aureus infection, one intraperitoneal and one intravenous, at doses as low as 0.25 mg/kg. In a third model, a lung infection in immunocompromised (neutropenic) mice, a single dose lowered the bacterial count in the lungs by more than 1,000-fold.

In the laboratory, LYSG101 was tested against more than 300 clinical isolates of S. aureus and coagulase-negative staphylococci. It inhibited 90% of strains at 2 µg/mL in standard broth and at 0.125 µg/mL in serum-supplemented medium, killed bacteria within 15 minutes, and broke down MRSA biofilms that vancomycin and linezolid left intact, with no toxicity in cell-based tests. Over 100 daily passages, none of the strains became resistant to LYSG101. In the same experiment, resistance to the comparator antibiotic mupirocin rose as much as 500-fold.

LYSG101 has already reached a patient. In 2025 it was given under an FDA compassionate-use protocol to treat a drug-resistant prosthetic joint infection that had not responded to standard care. The patient tolerated treatment without reported side effects.

The study, "LYSG101: a potent chimeric lysin with therapeutic potential for combating Staphylococcus aureus infections," is published open access in Antimicrobial Agents and Chemotherapy, Vol. 70, No. 6. DOI: 10.1128/aac.01730-25. https://journals.asm.org/doi/10.1128/aac.01730-25