Alphamers direct antibodies to fight bacteria
The threat of bacterial pathogens resistant to all existing antibiotics hanging over humanity has created an urgent need for fundamentally new approaches to the treatment of infectious diseases. Researchers at the University of California at San Diego recently conducted successful preliminary trials of one of these approaches, which consists in labeling bacteria with molecular "drive beacons" that attract antibodies available in the body to them.
The inventor of this beacon, called "alfamer", is the Nobel Prize winner Dr. Kary Mullis, the creator of a laboratory technique that has quickly found wide application around the world, known as polymerase chain reaction.
One end of the alphamer is made from a DNA aptamer, a short fragment of DNA identified in a pool of billions of candidate molecules due to its ability to form a strong bond with the target molecule. As part of the study, the authors used an aptamer specific to group A streptococci – bacteria that cause throat inflammation and invasive skin infections. The second end of the alphamer is represented by a carbohydrate molecule known as galactose-alfa-1,3-galactosyl-beta-1,4-N-acetyl-glucosamine, or, briefly, alpha-gal (alpha-gal). This carbohydrate is produced in the organisms of other mammals, as well as by some bacteria. In the process of evolution, the human body has learned to produce antibodies against alpha-gal, synthesized by microorganisms contained in the environment and entering the body with meat consumed.
Alphamers (purple) act as drive beacons that attract
alpha-gal antibodies circulating in the bloodstream (green)
on the surface of the bacterial cell membrane.
Experiments conducted on human whole blood have shown that alphamers not only bind to streptococci, but also attract antibodies against alpha-gal to the bacterial surface, which contributes to the absorption and destruction of streptococci coated with alphamers by cells of the human immune system.
The next stage of the work will be testing alphamers on animal models infected with multi-resistant bacteria, such as methicillin-resistant Staphylococcus aureus. The researchers hope that in the future the concept they have developed can be used to fight any bacteria and viruses, and possibly cancer cells.
Article by Sascha A. Kristian et al. Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer is published in the Journal of Molecular Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from UC San Diego School of Medicine:
Molecular Homing Beacon Redirects Human Antibodies to Fight Pathogenic Bacteria.
07.05.2015