A research collaboration between Harvard Medical School and MIT has identified a new class of antibiotics — dubbed halicin analogues — that kills methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae, and Acinetobacter baumannii through a mechanism of action so fundamental that bacteria appear unable to evolve resistance to it, according to a study published in Nature.

The Antimicrobial Resistance Crisis

Antimicrobial resistance kills an estimated 1.27 million people annually worldwide and is projected to exceed cancer as a cause of death by 2050 under current trajectories. The WHO designates MRSA, CRE, and Acinetobacter as Priority 1 “critical” pathogens for which new antibiotics are urgently needed. Yet the antibiotic pipeline has been functionally empty for two decades — no truly new class of antibiotics has reached clinical use since daptomycin in 2003.

The New Mechanism

The halicin analogues — the lead compound is designated SL-7 — disrupt the electrochemical gradient across the bacterial inner membrane by specifically inhibiting the bacterial ATP synthase subunit c-ring in a way that is structurally distinct from existing ATP synthase inhibitors. The mechanism is so deeply conserved and essential to bacterial energy metabolism that any mutation conferring resistance appears to be lethal to the bacterium itself — a phenomenon the researchers term “evolutionary entrapment.”

In 18 months of serial passage experiments — the standard laboratory method for evolving antibiotic resistance — no E. coli, MRSA, or Acinetobacter population developed resistance to SL-7 at concentrations up to 128× the minimum inhibitory concentration. By comparison, bacteria typically develop resistance to fluoroquinolones within days under the same conditions.

“We used AI to screen 107 million molecular candidates to find this compound. The AI found a mechanism we would never have found through traditional chemistry — and that mechanism appears to be evolution-proof.”

— Professor James Collins, MIT Synthetic Biology Centre, senior author

Animal Studies

SL-7 cleared MRSA bacteraemia in all 12 treated mice (vs 2/12 surviving in the control group) and eliminated carbapenem-resistant Klebsiella pneumoniae lung infection in a rat model with 91% efficacy. Toxicity studies in rats and non-human primates at doses up to 50× the effective dose showed no hepatotoxicity, nephrotoxicity, or bone marrow suppression — the three most common causes of antibiotic clinical failure.

Path to Patients

Roche has licensed SL-7 for clinical development. Phase 1 safety studies in healthy volunteers are expected to begin in Q3 2026. If safety is confirmed, a Phase 2 trial in MRSA bacteraemia — one of the deadliest hospital-acquired infections — will follow in 2027.

Regulators in the US, EU, and UK have all indicated willingness to use expedited pathways given the public health urgency. Researchers estimate SL-7 could reach patients in 5–6 years under optimal conditions.

⚕️ Medical Disclaimer: This article is for informational purposes only. It does not constitute medical advice. Always consult a qualified healthcare professional before making health decisions.