Bacteriophages instead of antibiotics
Snipers for pathogens
Sergey Avilov, Telegraph "Around the World"The standard therapy for almost any bacterial infection is antibiotics, that is, chemical poisons for bacteria.
Everyone knows that antibiotics have serious drawbacks: together with pathogenic microorganisms, they kill beneficial microflora and have side effects on a variety of organs. An additional inconvenience is the need to strictly follow the reception scheme. If you take the medicine irregularly or stop taking it too early, you can unwittingly develop antibiotic resistance in "your" microbe. An ideal antibacterial agent should act only on a certain pathogenic organism (the one that causes the disease), have no side effects and do not require strict adherence to the intake regimen. The most amazing thing is that such tools have long been known to scientists. These are bacteriophages – viruses that infect bacteria.
Healing waters of the Ganges RiverBack in 1896, the British bacteriologist Ernest Hankin (Ernest Hanbury Hankin, 1865-1939) reported that the waters of the Ganges and Jamna rivers in India have significant antibacterial activity, which persists after passing through porcelain filters with very small pores, but is eliminated by boiling.
Khankin suggested that some substance in this water is responsible for preventing the spread of cholera epidemics that may be caused by drinking water from these rivers.
In 1915, the British bacteriologist Frederick William Twort (1877-1950) discovered viruses that destroyed bacteria. And in September 1917, a scientist from the Institut Pasteur Felix D'Herelle (Felix Hubert d'Herelle, 1873-1949) presented a report to the French Academy of Sciences (Academie des Sciences), in which he reported that he had discovered an "invisible microbe" infecting dysentery bacillus. The scientist called his brainchild a "bacteriophage", that is, a "bacteria eater". Soon after, D'herel described a case of successful treatment of dysentery with the help of his "eater". Microbiology was in fashion then and was experiencing its "golden age", the idea of therapeutic use of bacteriophages was obvious.
Georgian microbiologist Georgy Eliava was also studying bacteriophages at the same time as researchers from the Pasteur Institute. In the 1920s, he opened an institute in Tbilisi, which engaged in phage research with a view to their therapeutic use and became a world leader in this field. In the 1940s, the pharmaceutical company Eli Lilly was commercializing phage therapy in the United States, but businessmen and doctors lost interest in it after the spread of antibiotics.
Weapons of non-mass destructionImagine that in order to destroy a group of terrorists, an entire village is burned down along with civilians.
Antibiotics work in much the same way. They can be compared with weapons of mass destruction – indiscriminately destroy everything: strangers, their own, cultural values, animals in the forest ... Antibiotics kill pathogenic bacteria, and at the same time useful intestinal microflora and mucous membranes, thereby providing favorable conditions for the existence of new pathogenic microorganisms. Most antibiotics have side effects: their use affects the kidneys, liver, inner ear and other organs. In addition, globalization and the widespread use of antibiotics have led to the spread of antibiotic-resistant bacterial strains. Smart terrorists have learned to hide from anti-terrorist operations while burning out a village with "peaceful" residents.
Bacteriophages, which differ favorably from antibiotics, can be compared with a group of snipers who know every terrorist by sight and aim to "shoot" only them. Bacteriophages are narrowly specific: each strain affects only a few strains of bacteria. For all other bacteria and for multicellular organisms, bacteriophages are harmless. They multiply in the cells of the "victim", so it is enough to introduce the phage into the body once instead of taking it regularly according to the scheme, as with antibiotics. When all the bacteria of this pathogenic strain are destroyed, the bacteriophages will have nowhere to reproduce, and they will "die out". Just like a Terminator: he killed everyone he needed, and then, just in case, he self–destructed - no matter what happened.
The well-studied bacteriophage T4 parasitizes Escherichia coli bacteria. The T4 virus consists of an icosahedral head containing viral DNA, a trunk, the base of the trunk and stem processes, six long and six short. The long appendages find the E.coli bacterium, and the short ones are firmly attached to the cell. The base at the same time transmits an impulse to the trunk, which contracts like a muscle, squeezing out viral DNA. The bacteriophage pierces the bacterial cell membrane with a special "rod" that extends as the base changes its shape, and through a nanometer-sized hole, viral DNA enters the bacterium. Knowledge of the mechanism of the bacteriophage injector will help in future methods of drug delivery. Illustration: Purdue University and Seyet LLC
Red Army virusesThe obvious advantages of phages from the point of view of pharmaceutical business and clinical practice turned out to be disadvantages.
The narrow specificity of bacteriophages requires that the causative agent of the disease be precisely known: only then can an "effective" phage be selected. So, before starting therapy, it is necessary to identify a pathogenic microbe: spend time, laboratory materials, man-hours of a microbiologist. It turns out too much hassle for the district therapist, to whom the patient came with an ordinary sore throat. Antibiotics are much more convenient: most likely, an antibiotic prescribed at random will kill the causative agent of the disease. If suddenly it does not kill, you can write out a second, a third.
In addition, high specificity implies the presence of a huge "arsenal" of phages – about as diverse as the "zoo" of pathogenic microbes. In practice, "cocktails" containing different bacteriophages are used. And for antibiotic therapy of almost any bacterial infection, not one, but another antibiotic from a rural pharmacy can be suitable. Bacteriophages are almost living organisms, they cannot be "synthesized" by tons in a chemical reactor, they can only be "bred" in the laboratory. In addition, bacteriophages belong to viruses: the very word often scares the patient. Pharmaceutical companies have their own difficulties in working with bacteriophages: viruses are objects on the border of the living and inanimate, there is no clear legislative framework for their patenting and registration as medicines.
Therefore, bacteriophages were of interest to scientists in the West, who are guided by the potential application of their results, only until they discovered antibiotics. The widespread use of chemical antibiotics has diverted attention from a better, but less "convenient" class of drugs. So far, no Western country has allowed the use of phages as a medicine. At the same time, scientists continued to actively study bacteriophages and use them as a convenient model for fundamental research in molecular genetics.
In the USSR, science was funded without regard to immediate profit, so phage therapy was more fortunate here: research at the Institute of Bacteriophagy, Microbiology and Virology named after him. Eliavas of the Georgian Academy of Sciences and other centers continued, and in the 1940s phage therapy was widely used, in particular, in the Red Army. Publications about the success of phage therapy were published in Russian and Georgian and were inaccessible to the scientific world behind the "Iron Curtain". If something became available, it was ignored, since the reputation of Soviet biology was greatly tarnished during the official non–recognition of genetics and cell theory - fundamental general biological teachings. However, in the USSR, antibiotics displaced phages. Now phage therapy is offered by the Phage Therapy Center on the basis of the Institute. Elavas.
The second coming of bacteriophagesIn recent years, the situation in the world has begun to change.
There is more and more data on the dangers of antibiotics; there are more and more strains that are resistant to many antibiotics; patients are more and more "fastidious" and wealthy: they do not want cheap and affordable therapy and prefer harmless and effective. Nowadays, the word "chemotherapy" scares the public more than the word "virus".
On the other hand, progress in molecular biology and biotechnology simplified the manipulation of phages and their "breeding", and the end of the Cold War made the achievements of Soviet scientists (especially Georgian ones) accessible to Western colleagues. In normal cases of infections, it makes no sense to "mess around" with bacteriophage therapy – standard antibiotic therapy also works. However, infections caused by strains that are resistant to antibiotics are increasingly common. In such cases, phages are the only effective means.
In 2006, the US Food and Drug Administration (FDA) recognized bacteriophages as safe as an additive that prevents the reproduction of unwanted bacteria on cheeses, and in 2007 they were recognized for other products, so now phages serve as a harmless preservative.
In the near future, more serious applications of phages are expected: Italian scientists Rosanna Capparelli, Marianna Parlato, Giorgia Borriello and their colleagues from the University of Naples. Federico II (University? degli Studi di Napoli Federico II) discovered a bacteriophage, called MSa, which destroys strains of staphylococcus resistant to the antibiotic methicillin – the main weapon in the fight against staphylococcal infection. Staphylococcus aureus affects many organs and systems and can lead to death in the absence of effective treatment. Currently, 40% to 60% of infections are caused by strains that are resistant to methicillin. It is in such cases that phage therapy can be indispensable. So far, encouraging results have been obtained in laboratory mice: MSa prevents death and completely destroys the Staphylococcus aureus bacterium in the body.
The Sydney-based company Special Phage Holdings has developed a method of treating infections caused by bacteria resistant to many antibiotics (the so-called multidrug resistant) with the help of bacteriophages, which are the main problem in modern therapy of infectious diseases. The technique is successfully undergoing clinical trials. And the company expects to be the first to capture a new sector of the pharmaceutical market in Australia.
In addition to using phages simply as "killers" of bacteria, other options are being considered. So, recently it was proposed to use bacteriophages as a Trojan horse. Scientists have long known that phages (like all viruses) have special molecular mechanisms for introducing their genetic information into the victim cell (the carrier is a DNA or RNA chain). Now scientists have figured out how to use this mechanism to inject a traditional antibiotic into bacterial cells. Such "nanoinjections" ensure effective delivery of the antibiotic precisely inside the bacterium-the causative agent of the disease, and not throughout the body, as happens with ordinary administration.
It took a long time to evaluate the benefits and possibilities of bacteriophage therapy, unfairly rejected by most scientists. But today the forgotten method is experiencing a rebirth and has every chance to become a very effective weapon in the struggle of a person with a hostile microcosm.
Portal "Eternal youth" http://www.vechnayamolodost.ru07.10.2008