Aptabiotics – Aptamers as the next generation of antimicrobial agents?
Research For Life
Reports of research work funded by grants prior to 2016
DJ Day, JP Soundy
School of Biological Sciences
The global increase in multi-drug resistant Gram-negative bacteria and paucity of new antibiotics entering clinical practice poses a significant threat to antibiotic therapy.
Recent studies have shown that short DNA or RNA molecules termed aptamers can be selected, using a process called SELEX, from a large random library of sequences for their ability to bind a specific target. Using the SELEX process we have isolated aptamers able to bind the opportunistic pathogen Pseudomonas aeruginosa with the ultimate goal of either using the aptamers directly as antibiotics or conjugating them to deliver other drugs to the bacterial cells. P. aeruginosa causes chronic infections in the lungs of cystic fibrosis that are highly resistant to antibiotic therapy, ultimately leading to premature death, as well as commonly infecting diabetic ulcers, where the bacteria form biofilms that impair healing causing significant morbidity.
We have developed bacterial species-specific DNA aptamers conjugated with an antimicrobial compound that is able to specifically bind to Pseudomonas aeruginosa rendering the otherwise multi-drug resistant bacteria, susceptible to antibiotic action. The aptamer-conjugates, that we call aptabiotics, have both intrinsic antimicrobial activity and synergistic activity with existing fluoroquinolone antibiotics that are used clinically to treat P. aeruginosa infections. We hypothesise that the use of aptabiotics is a generic approach for targeted antimicrobial therapy applicable to many pathogenic microorganisms.
On completion of the research we will have developed a novel type of antimicrobial drug that we believe is a significant advance with regard to treating bacterial infections that are recalcitrant to existing antibiotic therapy. This new health technology potentially will impact the treatment of a wide range of acute and chronic bacterial infections by making existing medicines effective once again.