New hazards require innovative solutions: preparing the next generation of antibiotics

Gonorrhoea, tuberculosis, salmonellosis… Not so long ago, illnesses like these were fatal. Antibiotics allowed us to treat them, but the overuse we have been doing of these drugs has a downside: bacteria have become so used to the antibiotics that they have developed defence mechanisms against them. As a result, some of these diseases have come back to bite us in the form of superbugs. This is such a pressing matter that 12 of these microorganisms have made it into a list of “most wanted” by the World Health Organisation. Of them, cases like Acinetobacter baumannii are specially worrying: some strains of these bacteria are resistant to even 6 different types of antibiotics.

Antibiotic resistance at a glance: how bacteria spread in a medium with concentrated antibiotic| Credit: Harvard Medical School

As bacteria get harder and harder to kill, researchers struggle to find new molecules that can serve as antibiotics. To find these molecules, we can look into the microorganisms that surround us. Since microorganisms have been fighting bacteria for millennia, evolution has provided them with highly tuned mechanisms that produce toxins that kill them. However, finding these compounds is a tough job, so we talked with Dr. Stefano Donadio, founder of Naicons, a company that specializes in finding these new molecules.

“We are outnumbered by bacteria billions to one, if not more. So there’s plenty of opportunities to find unusual microorganisms, even in our surroundings”, clarifies Dr. Donadio. At Naicons, they maintain, analyse and grow a very special library. One that is made not by books, but by 45000 microorganisms and the molecules they produce. “Gathering this library took an enormous effort. It involved between two and four people that worked for ten years gathering samples, isolating microorganisms and compiling them.” points out Dr Donadio

The microbiologists browse this library to find microorganisms that produce a fitting molecule that effectively fights a specific bacterium. In the past, many companies tested libraries such as this one by sheer brute force: they tried each component for different pathogens, hoping to identify which was more likely to be used as an antibiotic. “We want to be more cost-effective, so we do smart-screenings, in which we identify organisms that are good at synthesizing bioactive molecules. This way, we guarantee that we can use these organisms at an industrial scale in the future”, stresses Dr. Donadio.

Thanks to this refined process, less than a year ago Naicons identified PUM, a compound produced by a bacteria that was buried in Italian soil, that might be useful in the development of a new type of antibiotic against multi-drug resistant bacteria. In the testing done so far, this compound has proven to be effective against different types of bacteria. But the really interesting aspect of PUM lies in the profound reach of its effectiveness: it acts not only against the bacteria that infect the animals’ bodies, but in laboratory studies bacteria cannot easily develop resistant to it.

As promising as the results are, there is still a long way to go until a new antibiotic is produced. A critical point in this path is the scale-up of the manufacturing process to an industrial level. With the current technologies, this step can be especially tricky with bacteria: the antibiotic we want them to develop might kill them, by interfering in their internal processes. One of the answers to this challenge may lay in specific locations within the bacterial membrane: the lipid rafts. “We want to modify the bacterial lipid rafts, to use them as production compartments for antibiotics.”, explains Dr. Donadio. “In Rafts4biotech, we are trying this approach for the first time. To do that, we have chosen a very simple antibiotic, that requires few biosynthetic steps for the active molecule”. Using the rafts, lowers the toxic impact on the microorganism, avoiding interferences with their metabolism and viability.

“This would be a new technology to produce drugs.”, states Dr. Donadio, “We are testing it to produce one of our compounds, but the real interest lies in the broad applicability of the lipid rafts technology. From a biotechnology point of view, it is very appealing”. In the past, developments like vaccines, chemotherapy or the very discovery of penicillin, the first artificial antibiotic, gave us the advantage we needed to cure fatal illnesses. Today, technological advances like lipid rafts engineering can provide us the tools we need to face new challenges.

By | 2018-03-14T13:35:15+00:00 March 14th, 2018|R4B Biotechnology, R4B Stories|0 Comments

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