A new study published in the prestigious journal Nature has found that bacteria in a chaotic state are less sensitive to standard drug treatment. The researchers developed a statistical model that predicts the results of antibiotic treatment, and accordingly propose a new treatment strategy: Targeted introduction of the bacteria into a chaotic state – and healing of the cells using drugs that are specially adapted to this condition.
A new Israeli study has traced the behavior of cells in chaotic situations, in order to improve the quality of medical care. Its results were recently published in an article in the international journal Nature (Observation of universal “aging” dynamics in antibiotic persistence). The study was led by Prof. Natalie Balavan of the Rakah Institute of Physics, with student Yoav Kaplan and a diverse biodisciplinary research group that includes students in the Talpiot program (Shaked Reich and Alik Oster), Dr. of Biophysics (Orit Geffen) and Dr. of Biology (Ira Ronin). The study findings provide a new approach to describing cellular disorders. Whereas to this day, the prevailing opinion in the field has been that it is an orderly defense mechanism that prevents the bacteria from dividing properly, but in fact it is an unplanned chaos. Prof. Balaban explains that “even when we overcome a certain disease, drug treatment today, is not able to kill all the” bad “bacteria. “Bacteria in a chaotic situation, and drugs that harm bacteria in this particular situation, will be able to use their condition in a smart way to cure the disease.”
Bacteria are exposed on a daily basis to extreme conditions of cold, heat, food shortages and more. Luckily for them (and sometimes for our bad luck), evolution has led to the development of very sophisticated protection mechanisms for them: in response to external cold they produce materials that protect against cold and in heat conditions – produce materials that protect against heat, and more. The prevailing view is that the defense mechanisms of bacteria will work properly – or the bacterium will die. The research team discovered a new intermediate state of bacteria, after exposure to extreme conditions: “chaotic state”, an internal state characterized by disorders of the cellular state. This condition is created in the bacterium when its defense mechanisms are flooded and unable to overcome harsh environmental conditions. Despite this he does not die, but stops dividing and enters a state where his systems are in a chaotic state. It turns out that in such a situation, bacteria that stop dividing are more protected against antibiotics, because many of them are intended to impair the process of bacterial distribution. Moreover, most of the process of developing antibiotics is tested on dividing bacteria and not in a chaotic state.
As part of the study, the researchers collaborated with Prof. Oded Agam, from the Faculty of Mathematics and Natural Sciences at the Hebrew University, who specializes in the theory of statistical physics. Together they were able to develop a statistical model that could predict the results of antibiotic treatment. “One of the hallmarks of cellular disorders is that identical bacteria, such as twin bacteria with the same DNA, begin to behave in a very different way that doctors find difficult to understand and thus the effectiveness of drug treatment decreases,” explains Prof. Balaban. “In fact, it is a new line of thinking, according to which statistical physics is able to understand the behavior of cells in stressful situations and thus improve the effectiveness of the treatment of various diseases.”
In this way, the exposure and quantitative characterization of disorders in the normal state of the cells will allow the development of better medical treatments in the future. The researchers hope to be able to take advantage of the general features of the “cellular mess condition”, also to find smart combinations to treat cancer. “We can eliminate cells not only in their normal state, but also when they are in a non-standard and elusive state – something that may improve drug therapy and thus help us return to a normal life routine as soon as possible.”, Concludes Prof. Balavan.