Finding unique new strategies to combat bacterial infections that don’t employ the use of traditional antibiotics is not only challenging, but with the ever steady rise of microbial drug-resistance, it is essential. Yet, researchers at the University of Califorina, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences may have found a solution, publishing their current findings on a novel approach for eliminating bacterial pathogens.
The team of researchers generated a molecular homing beacon that tags the offending bacteria, which in turn attracts pre-existing antibodies to latch on and target the pathogens for clearance by the immune system.
The results from this study were published recently in the Journal of Molecular Medicine through an article entitled “Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer.”
The molecular beacon molecule was the innovative creation of Nobel Laureate and inventor of PCR, Kary Mullis, Ph.D., who is also a co-author on the current study. At one end of the molecular beacon is a DNA aptamer, which is a small piece of DNA created for its highly selective binding affinity—which in this case was for the common microbe that causes strep throat and skin infection, group A Streptococcus. The other end of the beacon contains the trisaccharide called α-Gal. Humans do not express α-Gal and often a large portion of our circulating antibodies are specific for the carbohydrate moiety, due to exposure from copious environmental sources.
The investigators set out to test their newly created homing beacon, or Alphamer, as they have dubbed it, on live strep bacteria. What they found was that the Alphamers not only bound strep and recruited anti-Gal antibodies to the bacterial surface, it also aided human immune cells to engulf and destroy the Alphamer-coated bacteria.
“Our next step is to test Alphamers in animal models of infection with multidrug-resistant bacteria that pose a public health threat, such as MRSA,” said Sascha Kristian, Ph.D., visiting research scholar at UC San Diego and lead author on the current study. “Meanwhile, we'll also be tweaking the Alphamer to make it more potent and more resistant to degradation by the body.”
The results from Dr. Kristian and her colleagues work provides the necessary in vitro proof that Alphamers have the potential to redirect pre-existing antibodies to pathogenic bacteria in a specific manner and trigger an immediate antibacterial immune response.
While the researchers are very excited about their initial findings, they acknowledged that further validation of their approach, especially for in vivo models of bacterial infection, is warranted.
“We're picturing a future in which doctors have a case full of pathogen-specific Alphamers at their disposal,” explained Victor Nizet, M.D., professor of pediatrics and pharmacy at UC San Diego and senior author on the current study. “They see an infected patient, identify the causative bacteria and pull out the appropriate Alphamer to instantly enlist the support of the immune system in curing the infection.”