How to Defeat Antibiotic resistance
Antibiotics collected in "irresistible" pairs
It is based on the study of how the resistance of microorganisms to some substances affects the sensitivity to others. The study is published in the journal Science Translational Medicine (Imamovic and Sommer, Use of Collateral Sensitivity Networks to Design Drug Cycling Protocols That Avoid Resistance Development).
The essence of the new method is to use several antibiotics of different nature to fight bacteria, which would replace each other in the course of treatment. Such an approach has been known since the 50s of the last century, but the new method has a fundamental difference - it is based on the study of mutual influence between different stability mechanisms.
The classical approach to the use of antibiotic rotation is based on the assumption that resistant bacteria are always less competitive than conventional ones. That is, if there are microorganisms in the environment that are both resistant and sensitive to antibiotic A, then if the drug is canceled, the resistant ones will always lose in competition with the usual ones. It was believed that when prescribing antibiotic B, which has a different mechanism of action, this rule is also fulfilled.
Rotation of antibiotics: black dots – sensitive cells, purple – resistant to A, green – resistant to B.
Image from the article in Sci. Transl. Med.
Scientists have shown that this is not always the case, since the formation of resistance to some substances can affect sensitivity to others, both in one direction and in the other (this can be seen in the diagram given by the authors). For example, the acquisition of resistance through the use of special molecular pumps that pump antibiotics out of the cell can make it more sensitive to substances that these pumps cannot pump out – simply by increasing the permeability of the cell membrane. If these pumps still bind an alternative antibiotic, then the cell becomes, on the contrary, "collateral resistant".
Table of mutual influence of antibiotics. In the rows – resistant strains, in the columns – drugs.
Image from the article in Sci. Transl. Med.
Scientists suggest using antibiotics in pairs, triples and other sequences where resistance to one increases sensitivity to the other. Then, if resistant bacteria appear when using substance A, when using drug B, they will be competitively displaced by ordinary relatives and only then the latter will be able to "learn" resistance to B.
Antibiotics are part of the natural arsenal of bacteria in the fight for ecological niches. Sometimes these relationships can be very complicated. For example, it is known that three strains of bacteria that 1) produce an antibiotic, 2) are resistant to it, but do not produce themselves, and those who 3) do not produce and are not resistant, in one ecological niche correlate like stone, paper and scissors (respectively) in the game of the same name.
Portal "Eternal youth" http://vechnayamolodost.ru30.09.2013