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Resisting antibiotic resistance with 2-AI
Raleigh, NC—The alarming and growing cases of antibiotic resistant bacteria and the diminishing number of effective antibiotics to fight infections is a well-documented global health concern. The World Health Organization ranks this as one of the top three threats to human health. Agile Sciences, a Raleigh, NC based biotechnology company, has developed a proprietary portfolio of small molecules of the 2-Aminoimidazole family (2-AI) that breaks the cycle of antibiotic resistance through a novel mode of action.
“It is not just a question of developing new antibiotics, which takes many years of research and significant cost, but rather targeting the bacterial protection mechanisms that will eventually make these antibiotics ineffective due to the onset of resistance,” said Malcolm Thomas, CEO of Agile Sciences.
According to Agile Sciences’ website, “Agile Sciences’ technology is based off of a marine natural product, ageliferin. Ageliferin is produced and secreted by a marine sponge, Agelas conifera, and prevents bacterial colonization of the sponge. Agile Sciences has identified and characterized the active pharmacophore of ageliferin resulting in an extensive library of synthetic small molecules that are active against a wide range of Gram-positive and Gram-negative bacteria that are relevant to pharmaceutical, industrial, and agricultural applications.
“Agile Sciences is developing novel 2-aminoimidazole (2-AI) compounds to enhance antimicrobial efficacy against difficult-to-treat bacterial infections. The 2-AI compounds act via a novel mechanism of action to interfere with the abilities of bacteria to sense and respond to their environment. This interference strips the ability of the bacteria to mount protective responses, such as biofilm formation and the expression of antibiotic resistance traits, to environmental threats. The bacteria are rendered defenseless and can be effectively eliminated with traditional antimicrobial approaches.”
The 2-AI compounds developed by Agile Sciences do not kill bacteria, but act by inhibiting the internal bacterial defense mechanism known as the Two-Component system (TCS). This inhibition prevents the bacteria from forming biofilms, producing toxins and developing resistance, thus allowing antibiotics do their job more efficiently. As an example, Malcolm Thomas cites the work done by Agile Sciences in treating Cystic Fibrosis (CF) — “in an animal model, we have seen marked improvement in the treatment of lung infections in CF, where an inhaled form of our compound disperses the biofilm that forms in the lungs resulting in the use of significantly less antibiotic to achieve clearance.”
The 2 AI compounds work not only with currently used antibiotics, but they are effective in re-activating older antibiotics. “These compounds re-potentiate older antibiotics that have been rendered useless by resistance as well as extend the useful life of current antibiotics,” noted Thomas. Agile Sciences announced that they will be presenting their research at the 5th One Health Congress in Saskatoon, Canada on Sunday, June 24th, 2018.