AFC vs Super Microbes
Resistant bacteria were defeated by old antibiotics with the help of light
Anna Kaznadzei, N+1
Biologists from the University of Colorado at Boulder have learned to increase the effectiveness of antibiotics due to nanoparticles that weaken bacterial cells. Nanoparticles activated by light initiated the synthesis of reactive oxygen species in cells and triggered a cellular defense response. After such treatment, antibiotic-resistant bacteria began to react to them much more strongly, and in some cases the effect of the drugs increased a thousand times. The study is published in Science Advances (Courtney et al., Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.
Antibiotics are an effective means of combating bacterial pathogens, but bacteria evolve at a tremendous rate, adapting to a variety of substances, and scientists have to invent more and more new drugs or even classes of drugs. Strains of bacteria resistant to a wide range of substances (MDR, multiple drug resistant) are constantly emerging, which pose a particular danger to host organisms.
It is known that ROS (reactive oxygen species) play a role in the interaction of bacteria and antibiotics, but so far the details of this role have not been completely clear. ROS are always present in the cell, however, when their concentration is excessive, antioxidant mechanisms of cellular protection are activated, since ROS can affect the structure of DNA, as well as disrupt the work of metal-containing enzymes. It is known that when the genes responsible for suppressing the synthesis of peroxides and superoxides are deleted, the susceptibility to antibiotics in bacteria increases. The researchers decided to study this phenomenon in more detail by artificially increasing the concentration of ROS in bacterial cells.
Within the framework of this project, scientists worked with resistant strains of three types of bacteria - Escherichia coli, Salmonella enterica and Klebsiella pneumoniae. Nanoparticles made of cadmium telluride, a semiconductor material, were injected into the cells, which could be controlled by activating at the right moment with light with a certain wavelength and generating a strictly specified potential. As a result, the nanoparticles emitted electrons, which, in turn, created the necessary ROS – superoxides (radicals *O2 –) in the cell from oxygen. Superoxides have a relatively long lifetime and a significant potential for action. By destroying sulfide bridges in metal-containing proteins, superoxides are able to create a flow of iron ions in the cell. Iron ions are localized in DNA, proteins and lipids and initiate the Fenton reaction.
This proved to be an effective way to weaken bacterial cells before treatment with antibiotics. In 75 percent of different tested combinations of "ROS + antibiotic", bacteria weakened by the action of ROS reacted significantly more strongly even to "old and familiar" antibiotics, both to bactericidal substances (ceftriaxone, ciprofloxacin and streptomycin) and to bacteriostatins (clindamycin and chloramphenicol). At certain concentrations, the effectiveness of the drug was increased up to 1000 times.
In addition to cell cultures, the technique was also tested on living organisms - nematodes Caenorhabditis elegans. It turned out that combination therapy allows about 20 percent more nematodes to survive, the intestinal microflora of which is affected by MDR bacteria, compared with nematodes that received only an antibiotic.
Scientists have calculated the depth of human skin, which can be worked with using this technique, and defined it as 1-2 centimeters. It is at this depth that the light from green LEDs, necessary for the activation of nanoparticles, will penetrate with sufficient efficiency. Thus, they believe, at the moment such a technique can be used to treat skin infections and burns. Scientists especially emphasize the importance of such developments to combat intracellular parasites, such as various types of Salmonella, since nanoparticles are small and mobile enough to penetrate first into host cells and then into bacterial cells.
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