A collaboration between the Hebrew University and the Shaare Zedek Medical Center produced a new study, published in the journal Science, and found that if substances are developed that prevent bacteria from reaching a state of tolerance, it will be more difficult for them to reach the resistance that threatens to put an end to antibiotics. "The goal is to trick the bacteria and prevent them from reaching their final destination"
Antibiotics save lives, there is no doubt about that, but more and more bacteria today manage to develop methods to overcome the antibiotic treatments and become resistant. The bacteria are helped by mutations that change their proteins, the same proteins that the antibiotics try to bind to, and as a result the antibiotics "skip" over them and do not harm them and the medical treatment fails. There are also mutations that allow bacteria to neutralize the entry of antibiotic substances into the cell or to remove them from it so that they do not harm them.
Two years ago, a scientific article was published in the journal Science about research carried out under the leadership of Prof. Nathalie Laban from the Rakah Institute of Physics at the Hebrew University, a researcher in the field of biological physics, which showed that bacteria are able to enter a state of temporary "coma" and stop their growth and thus escape antibiotic treatments, and later develop Antibiotic resistance 20 times faster than normal bacteria. The bacteria learned to remain in a "dormant" state, did not divide and were thus able to deal with antibiotics and thus develop tolerance to them. This is a survival stage for the bacteria, which allows them to develop and multiply without the antibiotics being able to harm them.
This tolerance feature intrigued Prof. Laban in the current study. In a new study published this week, also in the journal Science, Prof. Laban chose to examine the same trait of tolerance of bacteria in a number of patients who suffered from a blood infection at the Shaarei Zedek Medical Center. The current study was carried out in collaboration with Dr. Meschit Bar-Meir, director of the Pediatric Infectious Diseases Unit at Shaare Zedek Medical Center. The patients were in intensive care at the Jerusalem hospital, and their lives were in danger after being infected with a bacteria known as "golden staphylococcus", a virulent bacteria that can become resistant to antibiotics. Every day, for two weeks, blood was taken from them after antibiotic treatment - and the tests indicated that before mutations that confer resistance to the disease appeared, mutations that made the bacteria resistant to antibiotics appeared.
Drug resistance is a trait that is difficult to achieve quickly, because it requires the development of many mutations to fight high concentrations of antibiotics, with each mutation on its own giving the bacteria only partial resistance. Tolerance, on the other hand, is software that is easy to get to quickly and easily. In fact, tolerance in bacteria allows them to develop one mutation, enter a "dormant" state during exposure to antibiotics and then "wake up" and undergo another mutation and so on until reaching a state of resistance. The tolerance is a critical stage, which keeps the bacteria in a survival state that allows them to develop slowly and over time. Without the tolerance phase, the bacterium will not be able to develop in time the amount of mutations with which it will be able to fight antibiotics. According to Prof. Laban, the development of materials that will focus on eliminating the bacteria during the tolerance phase is necessary.
"There is currently no antibiotic tolerance test in hospitals, only a resistance test. Usually, different types of antibiotics are tried on each patient, until you reach one that is not resistant and you can adapt it to him. Unfortunately, time is not on the patient's side because they arrive at the hospital with a severe and life-threatening bacterial infection. Testing the tolerance phase is very important to know how many mutations the bacteria have had time to develop and which antibiotics the patient should use. A test that will allow doctors to assess which antibiotics the bacteria are tolerant to but not yet resistant to, will reduce the chance that they will develop antibiotic resistance. The goal is to trick the bacteria and prevent them from reaching their final destination, through controlling an intermediate state. In the following studies, we would like to perform additional tests in other hospitals in Israel, and we have even received offers from hospitals abroad to perform more extensive tests to check our latest findings," explained Prof. Laban.
