As the saying goes; “You never know the value of water until the well is dry.” Once new antibiotics seemed so abundant we ignored some as having little worth. But now multi-drug resistance is appearing with disturbing frequency, and finding unexpected ways to transfer between species, one previously unwanted antibiotic class has attracted renewed interest.
In the 1970s several teams studying the methods bacteria use to fight off others identified different members of the octapeptin group as having antibacterial properties. However, Dr Mark Blaskovich told IFLScience that at the time, 20-30 new antibiotics were being found a year, and octapeptins were neglected in favor of quite similar drugs called polymyxins.
Today polymyxins such as colistin are losing their effectiveness thanks to antibiotic resistance, but we are only finding 2-3 new antibiotics a year that even hold potential. So a team of scientists decided to give octapeptins another look.
It's too early to know if this return to the nearly-dry well will yield a true reward, but octapeptins are exciting due to their unusual capacity to kill gram-negative bacteria, a class that includes chlamydia, gonorrhea, and plague-inducing Yersinia pestis.
“Gram-negative bacteria are harder to kill as disease organisms, because they have an extra membrane to penetrate that is often hidden by a capsule or slime layer which acts to camouflage them from drugs and our immune system,” Professor Matt Cooper said in a statement. Terrifyingly, no new classes of antibiotics for gram-negative bacteria have been brought to the market for more than 30 years, and the pipeline of potential drugs is running very low.
Cooper and Blaskovich are co-authors of a paper, published in Cell Chemical Biology, that reports on the synthesis of more potent octapeptins, and shows these are effective in mice, even against bacteria resistant to polymyxins. In rodents at least, the new octapeptins are easier on the kidneys than colistin.
Blaskovich told IFLScience that the reduction in new antibiotics is partly because “we picked the low-hanging fruit”, but also reflects large pharmaceutical companies almost entirely abandoning the field.
Blaskovich explained that while cancer-fighting drugs may be taken for months and cholesterol-reducers for years, antibiotics do their job in days or weeks. Most infections can still be treated with cheap generic drugs – we need new versions for the potentially lethal, but fortunately still very rare, cases, so the profits are insufficient to attract big investors.
Cooper and Blaskovich hope to further enhance the potency of their drugs and get government and philanthropic funding for preclinical trials for whichever molecule looks the most promising. Even in the best possible scenario, however, it will be seven years before their work clears clinical trials. “That's why it is so important work starts now,” Blaskovich told IFLScience, “before the antibiotic resistance pandemic starts.”