Super-vancomycin
American chemists have created an antibiotic that kills "superbugs"
American biochemists modified the structure of the antibiotic vancomycin in such a way that it began to destroy microbes that developed resistance to the original version of this drug, according to the article Peripheral modifications of [Ψ[CH2NH]Tpg4]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics, published in the journal PNAS.
"Doctors can use this version of vancomycin without fear that microbes will develop resistance to its molecules. It acts on bacteria in three different ways, thanks to which its "survivability" has increased many times. Microbes simply cannot simultaneously look for ways to solve three different problems – even if they cope with one mechanism of action, the other two will definitely kill it," said Dale Boger from the Scripps Institute in La Jolla (in a press release New antibiotic packs a punch against bacterial resistance – VM).
In recent years, the problem of the appearance of so-called "super–bacteria" - microbes resistant to the action of one or more antibiotics - has become more and more acute for doctors. Among them there are both rare pathogens of infections, and very common and dangerous pathogens, such as Staphylococcus aureus or Pneumococcus (Klebsiella pneumoniae). There is a real danger that all antibiotics will lose their effectiveness and medicine will return to the "dark ages".
The main "incubators" of such microbes, according to scientists today, are hospitals and livestock farms, where antibiotics are used to accelerate the growth of meat breeds of livestock. Both on farms and in hospitals, large numbers of potential carriers of infection, bacteria themselves, and antibiotics are concentrated, forcing them to evolve and preventing "ordinary" bacteria from displacing less prolific super-microbes.
According to Bowdger and his colleagues, they managed to find a potential solution to this problem by modifying one of the "antibiotics of last resort", vancomycin, to which some microbes have already begun to develop resistance due to the fact that it has been used in medical practice for about 60 years.
Bowdger's team has been developing new versions of this antibiotic for several years, when creating which scientists are not just trying to increase its effectiveness, but to make the molecule "invulnerable" to evolutionary processes that cause microbes to turn into "superbugs".
To solve this problem, scientists analyzed the three-dimensional structure of vancomycin molecules and tracked how it interacts with the cell wall of microbes, and also identified all the "weak points" in the molecule that bacteria neutralize in the first place.
Guided by these observations, biologists identified the three most active points in the molecule and changed their structure so that each of them could independently connect to the bacterial cell wall and interfere with its normal "assembly" and operation. Some of these changes were already present in the derivatives and analogues of vancomycin, which facilitated the task of their "transplantation" into the original antibiotic.
Figure Boger Lab – VM.
The product of all these changes was a new molecule whose antimicrobial activity was 25 thousand times higher than that of a simple vancomycin. At the same time, it suppressed reproduction and killed even those microbes that had developed complete resistance to its "progenitor", including enterococci that cause infections of the gastrointestinal tract in hospitals. Moreover, the antibiotic has not lost its strength even after 50 attempts to multiply microbes in its presence.
As scientists expect, this version of vancomycin should live no less than its progenitor – about 50 years before microbes begin to develop resistance to it. Moreover, Boudger and his colleagues believe that bacteria will not be able to adapt to such a "triple" attack in principle, provided that vancomycin derivatives with one of three similar changes will not be used in the future.
The main problem of this improved "version" of the antibiotic so far is the complexity of its production – it includes 30 different stages and quite complex reactions. According to Bowdger, this is not a problem, and their number can be reduced today to 26 or even 18 steps, and in the future to even smaller numbers.
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30.05.2017