Novel substances for the treatment of antibiotic resistant bacteria
Almost one century after the first systemic administration of antibacterial compounds, bacterial pathogens continue to threaten human health as medications are increasingly made ineffective by the development of bacterial resistance. This development is an unintended adverse event of any process that involves bactericidal or bacteriostatic activities. Since an antibiotic-induced selection of resistant pathogens seems to be unavoidable, it is now opportune to consider another option: instead of interfering with the bacterial life cycle, it is desirable to selectively attenuate microbial damage to individual host cells by boosting their non-immune antibacterial defences.
We have generated mixtures of uncoated and empty liposomes composed exclusively of naturally occurring lipids. Consisting of large, extracellular surfaces, liposomes serve as bait for bacterial virulence factors and efficiently compete with cells for toxin binding in vivo, when both liposomes and host cells are simultaneously targeted by the toxins. In vitro, liposomes sequester the released toxins thus preventing cellular damage and, in a mouse model, efficiently protect the animals from fatal septicaemia and pneumonia either alone or in combination with antibiotic treatment. By liposomal toxin sequestration, the entire organism can be protected from a potentially fatal reaction of the immune system to toxin-induced cellular injury.