New antimicrobial agents, peptides show promise in fighting multidrug-resistant bacteria
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Innovative antibiotics and antimicrobial peptides may dispel the threat of antibiotic resistance, but a joint effort of governments with the pharmaceutical industry is required, according to one presenter at the virtual EuCornea congress.
“On average, $2.5 billion are spent developing a single antibiotic, and that is not profitable for big pharma who have to make money for themselves and for the shareholders. My take is that governments have to join with industries not only in combating antimicrobial resistance, but also in developing new antimicrobial agents,” Harminder Dua, MD, PhD, said.
The WHO records 51 antibiotics currently in trials, of which only 17 are innovative, and it is anticipated that only 10 of these will make it through drug development to market within 5 years.
“One of them is teixobactin, a very novel antibiotic with a unique mechanism of action in that it binds to large clusters of lipid II, which are the building blocks of the bacterial cell wall,” Dua said.
Cefpodoxime and halicin are both showing efficacy against multidrug-resistant bacteria. The first inhibits bacterial beta-lactamase, increasing the efficacy of beta-lactam antibiotics. The second disrupts the flow of protons across the cell membranes of bacteria and has the additional advantage of low toxicity.
“Halicin is unique also because it was developed through a method of AI, based on the neural network developed by Collins that can learn new patterns unknown to human experts,” Dua said.
Antimicrobial peptides, or host defense peptides, are the eukaryotic analogs of antibiotics. They are considered part of the innate immune system but also serve as a link between the innate and the adaptive immune system. Defensin and cathelicidin are the most common families.
“Thanks to their mechanism of action, which consists of punching holes in the cell membrane, there is very little chance that organisms might develop resistance to these agents,” Dua said. “They can be used individually or in combination with antibiotics, boosting their efficacy against bacteria.”
Finally, Dua spoke about the possibility of using the stromal lenticule of femtosecond laser-assisted stromal lenticule addition keratoplasty as a sustained delivery strategy.
“Decellularized lenticules can be impregnated with microparticles for antimicrobial effect, providing sustained delivery of the drug at the site of action,” he said.
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Dua H. Antimicrobial agents to antimicrobial peptides: The past and the future. Presented at: EuCornea congress; Sept. 26, 2020 (virtual meeting).
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