To spare host cells the depredations of bacterial toxins, artificial liposomes may be sacrificed during severe bacterial infections, say scientists based at the University of Bern. The artificial liposomes, which are composed of naturally occurring lipids and mimic specific cell-surface microdomains, are tailored to compete with host cells for toxin binding. Because the artificial liposomes are not bactericidal—they disarm bacteria by sequestering virulence factors—they impose little or no selective pressure on bacterial growth. That is, they do not promote bacterial resistance.
This last point is especially important in light of repeated warnings from the WHO and other organizations about the growing emergence of antibiotic-resistant bacteria, which already kill some 50,000 in the United States and Europe each year.
The artificial liposomes consist of a novel substance engineered by Eduard Babiychuk, Ph.D., and Annette Draeger, M.D., researchers at the University of Bern’s Institute of Anatomy. Hoping to make the most of the liposome’s toxin-baiting ways, the researchers are working with Lascco, a Swiss-based biotech startup, to develop lipid-based nanoparticles as a new medicine, now called CAL02. Both the University of Bern and Lascco issued press releases that heralded positive results from a preclinical efficacy study.
These results appeared November 2 in Nature Biotechnology, in an online article entitled, “Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice.”
“Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by Staphylococcus aureus and Streptococcus pneumoniae, whereas untreated mice die within 24–33 h,” wrote the study’s authors. “Furthermore, liposomes protect mice against invasive pneumococcal pneumonia.”
The authors emphasized that liposome-bound exotoxins are unable to lyse mammalian cells in vitro. “We have made an irresistible bait for bacterial toxins. The toxins are fatally attracted to the liposomes, and once they are attached, they can be eliminated easily without danger for the host cells,” said Dr. Babiychuk.
According to Lassco, 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.
“These in vivo studies strongly support our decision to conduct a first-in-human study next year in severely ill patients with pneumococcal pneumonia,” commented Samareh Azeredo da Silveira Lajaunias, managing director at Lascco. “This new drug meets crucial medical needs, since virulence factors such as toxins are responsible for serious infection-related complications. These complications concern 23% of individuals affected by community-acquired pneumonia, extend hospitalization in intensive care units, and tremendously increase the cost of care.”