Over recent years, there has been a rapid increase and spread of gram-negative bacteria that show resistance to many or all existing treatments. The resistance and pathogenicity of these superbugs are even made worse by the presence of polysaccharides in the bacterial cells, which hinder the penetration of antibacterial drugs.
As of now, there are still no approved antibiotics that target the polysaccharide region of bacteria. In a new study, researchers developed the first lipid nanoparticles to eliminate bacterial polysaccharides from hypervirulent pathogens.
Potential of Antimicrobial Lipids
Antimicrobial lipids refer to free fatty acids, sphingolipids, monoglycerides, cholesteryl ester, and other compounds that can inhibit bacterial growth through various mechanisms. They have been recognized as broad-spectrum antibacterial agents directly acting on lyse bacterial cell membranes.
Naturally occurring antimicrobial lipids are important components of the innate immune system in human skin and are less likely to cause bacterial resistance than traditional antibiotics. Although these lipids demonstrate activity against problematic bacterial pathogens, their application is usually hindered by their low solubility and permeability.
To overcome these issues, extensive research has been conducted into developing lipid nanocarriers that encapsulate and deliver antimicrobial lipids. However, other critical issues need to be addressed, such as low drug-loading capacity and the complexity of the components in formulation.
Polysaccharide-Targeting Lipid Nanoparticles
At Monash University, a team of Australian researchers developed a new method of fighting antibiotic-resistant bacteria that uses lipid nanoparticles that target specific layers on the surface of their bacterial cells. Their study shows the possibility of delivering antibacterial lipids combined with established treatments to treat bacterial infections.
Led by Professor Jian Li, Professor Anton Peleg, and Associate Professor Hsin-Hui Shen, the scientists utilized neutron reflectometry to understand the structure of cell membranes at the nanometer scale. They used the Platypus instrument at the Australian Center for Neutron Scattering to elucidate the mechanism in a combined ML-noisome/polymyxin B treatment at the molecular level.
Polymyxin B is a type of antibiotic that is used as a last resort to treat infections from gram-negative bacteria. However, some bacteria show signs of resistance even to this antibiotic.
To address this problem, the team made artificial membranes that mimic the properties of the cell surface of gram-negative bacteria. It was found that the ML-niosomes target the outer layer of the outer membrane, primarily composed of polysaccharides.
The outer membrane gets exposed as its surface is bound to the ML-niosomes. This gives polymyxin B better access for attacking and breaking down the protective outer membrane and the inner membrane, ultimately killing the bacterial cell. This new method was also effective against many hypervirulent strains of Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and other multidrug-resistant pathogens.
In the future, the researchers plan to investigate how this mechanism is achieved at the molecular level and why combining it with polymyxin B is more effective. They will expand their study to test against other pathogens resistant to established treatments.
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