Preventing antibiotic resistance: Bacterial-toxin catcher snatches lethal infections

Antibiotic resistance has become a hot topic. Antibiotic-resistant bacteria kill some 50,000 in the U.S. and Europe each year but little can be done except develop new drugs because the risk of the emergence of resistance is inherent to their use. Pharmaceutical companies, jaded by short sales windows before products become generic, a daunting regulatory cycle and costs for trials that can be over a billion dollars, are pursuing novel drugs that have some chance of return rather than iterations of antibiotics. Regulatory bodies, aware that governments are ill-suited for product development, are not scrambling to streamline the regulatory process or change patent laws so antibiotics may be worthwhile again.

In the interim, other groups are searching for ways to stop resistance from happening. One example is a new broad-spectrum therapy that acts alongside antibiotics to indirectly impede bacterial growth, which allows the immune system to better combat the infection while also hindering the emergence of resistance.

In Nature Biotechnology, a study has reported positive preclinical efficacy for a new liposomal agent can act as a decoy to neutralize damaging bacterial toxins and rescue mice from fatal bacteraemia and pneumonia. The work led by Dr. Babiychuk and Professor Draeger of the University of Bern shows that by mimicking specific cell-surface microdomains, CAL02 neutralizes bacterial toxins and thereby significantly improves the survival of mice infected with a lethal dose of Streptococcus pneumoniae or Staphylococcus aureus and protects against clinical deterioration.

CAL02 is a broad-spectrum anti-virulence therapeutic agent for the treatment of severe bacterial infections, including those caused by antibiotic-resistant strains. It consists of two lipidic nanoparticles exclusively composed of ubiquitous dietary lipids constituents of the mammalian membranes. CAL02 acts in synergy with the antibiotics and also indirectly affects bacterial survival by depriving bacteria from the tools they use to feed and multiply, and by protecting the immune system, which can then appropriately combat the infection. The product is at preclinical stage.

The company behind it, LASCCO SA, says the drug will enter clinical phase next year in patients affected by severe pneumococcal pneumonia.

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