Fighting the onset of antibiotic resistance has involved making many modifications to antibiotics either via chemical synthesis or by natural procedures. But now a change in strategy is required. Scientists are engaging in finding entirely new antibiotics. The EU-funded project, DIVINOCELL, has succeeded in finding new compounds that could attack highly resistant gram-negative bacteria by interfering with their proliferation. Project coordinator, Miguel Vicente, talks to youris.com about the need to invest in basic research to study how bacteria proliferate, should society not want to return to the pre-antibiotic era, when many infections that are now easily cured were deadly diseases.

Why are some patients unable to be treated by certain antibiotics?
All the microbes living in the environment, bacteria among them, fight against each other to win the scarce nutrients available. If one microbe produces a compound, an antibiotic, that is able to kill all the other microbes around, then all the nutrients available in that particular place will be for itself. Thus, over time, sensitive bacteria have reacted by developing resistances to antibiotics. Once resistant, the bacteria are immune to the antibiotic and the microbe that produced it loses its advantage. Microbes have played this strategic game from their origin to the present day. And as we have been using antibiotics for a long time now and they have often been used indiscriminately, many pathogens that were once sensitive have acquired resistance. Consequently, now, more infections are caused by antibiotic resistant bacteria, which cannot be treated with the antibiotics commonly available.

What kind of solutions have been available?
If the infection is caused by sensitive bacteria, it is treated with the antibiotic that is most effective. Or, with a combination of two antibiotics. It is also possible to use some compounds that can counteract resistance. Most of the antibiotics similar to penicillin that are used nowadays are in fact a chemically modified version of penicillin. They share parts of its structure, but they contain some synthetic parts that allow them to overcome resistance. The other alternative is to find novel antibiotics.

What innovative approach have you been involved in?
So-called Gram-negative bacteria, such as E. coli, are more resistant to commonly used antibiotics. This is because they are surrounded by a cover that is more complex than the one present in other bacteria. As a result, it prevents antibiotics like penicillin from entering easily. In the project, we obtained information about the behaviour of the machinery E. coli uses to proliferate. This will help companies to target the compounds that are effective in killing it. Each of the four biotech companies participating in the project obtained a few compounds that can specifically block the proliferation of some Gram-negatives. Even though the project is finished, these initial compounds are still being studied to try and make them more effective than the original compound.

What are the main outstanding challenges in the fight against antibiotic resistance?
Now it is more difficult to find new antibiotics. And, given that proving drug safety for human patients requires staying within the strictest of limits, it is very difficult to get them approved for clinical use. An additional problem is that the antibiotics are very good medicines in the sense that they cure. But they are very poor drugs to sell because once the patient recovers they are no longer needed. This is not very attractive for pharmaceutical companies who need to recover investment by selling medicines.