MOSCOW, December 6. /TASS Correspondent Irina Skalina/. The Arctic Floating University's regular expedition this year featured three microbiologists from different scientific institutions. They had different tasks, though in one direction: to find new ways to resist pathogenic bacteria. TASS correspondent joined the scientists in swabbing bacteria on Petri plate and in searches for biocenoses.
Expensive remedy for infections
The antibiotic resistance problem is growing. Scientists forecast microorganisms very soon may stop responding to all existing antibiotics.
When this happens, the humanity may retreat to the 19th century, where any wounds were potentially fatal, pneumonia was lethal, childbirth was a very dangerous process, and the average life expectancy was decades shorter. Hospital-acquired infections are a very serious threat to humans nowadays. Quite often, antibiotics are not helpful, and no one can be guaranteed against such a pathology.
Producing antibiotics is very expensive. Pavel Nazarov of the Lomonosov Moscow State University (MGU) said the cost of the process from development to taking to market is about $1.5-2 billion. At the same time, microorganisms get resistant to antibiotics fantastically quickly - it takes them just months, not even years. The resistance genes, found, say, in China, get to Spitsbergen within five years, and thus the global bacteria develop resistance to another human invention.
Exotic islands and their inhabitants
Bacteria fight their own kind, including with the antibiotics, which they produce. New antibiotics may be found in various exotic locations, and the polar regions are among them. In high latitudes, for example, lives polar bear. In its microbiota (a combination of bacteria, fungi and viruses in the body) it is quite possible to find a substance against Staphylococcus aureus. Additionally, the Arctic is a region with many bacteriophages. Those are antimicrobial drugs of natural origin. The Arctic is a point of their biological diversity.
- Hence the scientific task is to study how these Arctic phages may be used to contain infections in humans, in particular the infections against which antibiotics are ineffective, and first of all bacterial nosocomial (hospital-acquired) infections. Therefore, we have planned a long-term project, we want to screen various ecosystems in the high-latitude Arctic to find the phages, which may destroy various bacteria, - said Artemy Goncharov, head of the Functional Genomics and Proteomics of Microorganisms Laboratory at the Institute of Experimental Medicine.
He participates in the Arctic Floating University expeditions for the second year in a row. A year earlier, the scientist made a collection of Arctic bacteria. This time, additional species have been added to the collection, and experts will examine them to find any "interesting phages" which can kill pathogenic microorganisms.
Happy chances
The microbiologists now resemble Dan Brown's characters looking for something to save the humanity. Like it happens in science fiction books, the work of our scientists has a certain touch of luck. Associate Professor of Microbiology at the Medical Institute of the Peoples' Friendship University Nadezhda Sachivkina has delivered a lecture to the expedition participants, telling them about how British microbiologist Alexander Fleming discovered penicillin. To an extent, it was luck. The legend is that on a hot summer day the scientist was swabbing staphylococcus, and left a half-eaten pumpkin nearby. Those objects remained in the lab while he was away on a trip. Mold grew on the pumpkin, got onto the cup with staphylococcus, and bacteria died where the mold had reached them. This is how the first antibiotic was discovered.
Nadezhda has joined the expedition to find red, or pink, snow. The coloring comes from the Chlamydomonas Nivalis (snowy chlamydomonas) algae. A colony of chlamydomonas may become visible if the snow is old, if it has remained on the ground for more than one year, which is possible in the Arctic or in Antarctica. The microbiologist stressed she had asked the expedition organizers how realistic it would be to see colored snow. They assured the expert that at least once, though on every voyage, this kind of snow had been seen. Exactly like it happens in good novels, red snow was seen during the very last trip ashore on Novaya Zemlya.
- I found it in Ivanov Bay, it was our last landing on snow. It was purely a matter of luck. We faced a choice: go to the left - see a canyon, go to the right - there's a bird colony. My colleagues preferred the bird colony, and I wanted to see the canyon with old snowfields. Luckily, we've managed both.
Chlamydomonas contain special compounds called terpenoids. They can be active against microbes and fungi, though not by themselves, but when added to existing drugs.
- We will compare their activity with standard drugs - they may be very weak, or very strong. Or perhaps they will not have a particularly strong effect on bacteria and fungi, but when added to known chemical elements or antimicrobials, they may increase the potential, - Nadezhda said, adding since is it very expensive to develop new antibiotics, researchers have to use alternative approaches. - Labs and scientists have changed the focus: let's learn to work with what we have. We will upgrade, make add-ons, additives. We will attach an additive to our "old pistol", and it will work well, sending the "bullet" even further.
Bacteria vs bacteriophages
On one hand, there are many different places where microbiologists can collect bacteria and bacteriophages: from shallow reservoirs to bird colonies and even lemming and vole burrows. On the other hand, experts have to search at a maximum number of potential locations to collect maximum samples.
Bacteriophages have been used to treat infectious diseases. They are eyed as promising drugs for nosocomial infections. They can be used in combinations with antibiotics, or specialists may make a phage with certain elements, or just antibiotics, or, for example, photosensitizers - the molecules that, when absorbing a quantum of light, release an active form of oxygen thus oxidizing lipids and proteins and destructing cell walls of microorganisms.
- We will try to find phages on the collected bacteria, and in addition we have an extensive collection from hospitals in St. Petersburg and other cities, - Artemiy Goncharov said. - We really hope to find phages that will be active against the bacteria from the second collection, since it is the most interesting and important part. We will continue to study such phages in terms of including them in therapeutic or preventive drugs.
Heroic bacteria
Bacteria are far from being simple: they can communicate with each other, can share with others the developed defense mechanisms. They even die heroically so that others could live. This explains their successful life and fight against us. According to Pavel Nazarov, "bacteria are practically eternal." Biofilm or bacterial mats are a more common community form in high latitudes: microorganisms live in a colony, where those in outer layers die so that the others could survive. The researchers were specifically looking for biofilms to sample them.
- Those are microbial structured communities that have upper layers of cells, which could be sacrificed if they die. The surviving cells use their resources, and, on the other hand, the dead cells plus the mucus they have formed perform the function of a thermal insulation for the bacteria inside the colony. This is very similar to pillow-shaped plants, which the girls from NAFU (Northern Arctic Federal University) have studied. They found the temperature inside those pillows was slightly higher than outside. Here we can see a similar situation, - Pavel Nazarov said.
The biofilms research is necessary for a project to study bacteria's protective systems from bacteriophages, the so-called retron systems. Retrons are known to encode molecules that carry out antiviral protection of bacteria, thus forming innate immunity. It works as follows: when a virus attacks a cell, a special protein kills the cell affected by the virus. This happens very quickly, viruses do not have time to multiply and infect neighboring cells.
- We will test the bacteria that we will receive to see whether they have these special protective systems of retrons. While in tropical latitudes such a system of protection against bacteriophages may or may not be useful, because most of the population is swimming, and only some part is in the form of biofilms, in the North there are a lot of biofilms," Nazarov said. - At the same time, the conditions there are such that it is difficult to survive. Water systems, lakes are limited, and if only bacteriophages could get there, it would have caused a big collapse of these systems. Here, of course, has been a tougher survival selection since their retron-type defense system is stronger than it had been assumed. This is a guess, it simply needs to be checked.
Mysterious pumps
Microorganisms use three mechanisms of exchanging genetic information: transformation, transduction and conjugation. Nadezhda Sachivkina compares them to passing of a sheet of paper. In conjugation, the exchange is direct: one bacterium builds a bridge to another and uses it to transmit DNA. In transduction, DNA is delivered by a courier - a bacteriophage carries the information. And transformation is like a testament. The "naked" DNA from the dead bacterium is embedded into the bacterial cell.
Bacteria keep genetic information also in plasmids (extra-chromosomal DNA molecules capable of autonomous creation of daughter molecules). These molecules carry 40-50 genes. They are able to deliver information from bacteria to bacteria about such a mechanism of protection against antibiotics as multidrug resistance pumps (MDR). These pumps "pump out" antibiotics from microorganisms, and bacteria do not die.
- Earlier, scientists thought complex multicomponent pumps cannot be transmitted from one bacterium to another. However, we have learned quite recently that some proteins of such pumps can be transmitted using plasmids and can form functioning MDR pumps," Pavel Nazarov said. - If such a MDR transfer from bacteria to bacteria is possible, it changes the world picture in terms of understanding the bacterial resistance transmission processes. We want to use Arctic bacteria to demonstrate how it all works in nature.
To put it in simple words: by studying Arctic bacteria scientists may understand how they transmit to each other the protection against antibiotics.
Antibiotic sensitivity testing
Arctic samples will be used for another project - to create a quick system to determine how much a pathogen is sensitive to antibiotics.
- What's the routine we know: a smear is taken, brought to the lab, they grow bacteria there for three or four days. If they haven't grown anything, then you don't know anything. When I got sick with COVID and the doctor suggested I also had a bacterial infection, they took a smear, had it grow for four days, - Pavel explains that, unfortunately, this is quite a common situation, while within four days bacteria can cause significant damage to the body. - We assumed that we can create a certain system, where within 6-12 hours we will get information about how antibiotics act on a specific bacterium in a particular patient. We have developed this system, but in order to apply it, we need some completely unusual organism - not something that we can do in a standard lab, but something new.
This new is what the scientists are bringing from high latitudes. In order to prove the system works, it will be tested on microorganisms from the Arctic, with which nobody has worked earlier. If scientists see results on them, then the system very probably will also work on bacteria that live in hospitals.
Years-long studies
Such studies take years. For example, in the found promising phages scientists will decipher the genome, conduct electron microscopy, and describe the virus properties. Only after that, they can proceed to preclinical and clinical trials.
Experts have some results from the expedition of 2021. That year, it was for the first time they collected samples on Franz Josef Land's islands. The tests were important for working out the methods, Goncharov said.
- We wanted to understand which bacteria are where, where to look for them in the high-latitude Arctic. Well, for example, lakes and bird colonies are places with high concentrations of various types of microorganisms.
On Spitsbergen, scientists have found bacteria that are resistant to all currently known antibiotics. No such super bacteria have been found on Franz Josef Land - some bacteria are sensitive to some antibiotics though resistant to others.
- For example, we've found there a strain containing beta-lactamase, which earlier was described in strains associated exclusively with humans, that is, the antibiotic resistance gene, which is assumed to be of human origin. It was found in urban sewage systems. The import of antibiotic resistance to the high-latitude Arctic is underway most likely. This is important since antibiotic-resistant bacteria can stay in the cold Arctic environment and in lake sediments, in water, they will exist there for many years. Whatever they are bringing can remain there for a long time.
Most likely, migratory birds carry such bacteria, since the samples were taken on the islands where no people live.
According to Goncharov, work on the project will continue also in Antarctica. He is heading for another polar expedition. This time - to the Far South.