Laboratory experiments show that when infected, their population decreases, which is why they are called bacteriophages, experts explain.
Mexico City, August 28, 2023. Last year, biologist Victor Manuel González Zúñiga received an unusual phone call asking for help.
It was from a desperate man whose father was in intensive care with a severe bacterial infection from the same hospital where he was operated on.
Given the ineffectiveness of antibiotics, there seemed to be only one last and unusual alternative.
“They called me to see if there were viruses in my lab that they could use (to care for him),” recalls González Zúñiga (Posa Rica, 1961), researcher at the UNAM Center for Genomic Sciences (CCG) in an interview.
Although his answer was no, since at that time he was not particularly interested in the clinical field, the idea of fighting bacteria with viruses was not alien to him, a professor of basic biomedical research and a doctor of biotechnology, who mainly focused on the study of Rhizobium, a genus of bacteria that can fix atmospheric nitrogen – to bio-fertilize – and thus establish a symbiosis with the plants they infect.
“When we started looking at the diversity of these bacteria, we also found the viruses that they have and that their populations decrease when infected with them. This class of viruses that specifically infect bacteria is called bacteriophages (or simply phages). And Rhizobium is no exception,” says González Zúñiga.
“So, this is where we started working with viruses a few years ago: with Rhizobium bacteriophages, a beneficial bacterium,” he confirms. “It’s estimated that for every bacterium in the world, there are 10 different bacteriophages that can attack it.”
The therapeutic use of these bacteriophages – viruses that “eat bacteria” due to their etymology – or phage therapy, although at first glance it may seem somewhat counterintuitive, is actually happening in different parts of the world, although mostly little by little. And this is far from a new approach or discovery.
The French-Canadian microbiologist Félix D’Herelle (1876-1949), hired in 1908 by the Mexican government to extract alcohol from the remains of a henequen, around 1917 was the first to confirm the presence of a new type of virus: a transmissible object capable of killing bacteria, that the Englishman Frederick Twort (1877 -1950) foresaw many years ago.
“(D’Herelle) immediately thought they could be used to treat (patients) or kill infectious bacteria in humans,” Veracruz biologist says of a French-Canadian who used phages to fight cholera and typhoid fever in the 1990s years. 30s of the last century, on the territory of the then Soviet Union, where the George Eliava Institute of Bacteriophages, Microbiology and Virology was even created.
However, in the West, the era of antibiotics, initiated by Alexander Fleming (1881-1955) with the discovery of penicillin, has taken precedence over any other clinical possibility.
It was only relatively recently, when various bacteria developed dangerous antibiotic resistance that became a serious threat to the hospital environment, that bacteriophages suddenly became a valuable option.
“Obviously, antibiotics were a huge success, but later we started to see that populations of bacteria began to emerge that were not only resistant to a single antibiotic, but also multidrug-resistant.” “New antibiotics appear, and there the bacteria also immediately react; it has its own evolutionary strategies that make it resistant to the new antibiotic.”
“Now, with the emergence of new methods, as well as the problem of antibiotics and multi-resistance, various alternatives are obviously being sought,” González Zúñiga repeats.
First steps
After this call for help, to which he was unable to respond positively, González Zúñiga decided to explore this route and start working with some bacteriophages.
He began by looking at the bacterium Acinetobacter baumannii, already well known to some colleagues in his laboratory; “This is one of the scourges of the clinic: it is multidrug-resistant, highly opportunistic, and is now spreading easily in many hospitals,” describes a biologist from Veracruz.
Through bioinformatics-type work, the scientist and his team discovered various bacteriophages and even found evidence that the viruses that infect this bacterium are partly responsible for its ability to resist antibiotics, as they transfer its genetic material.
“This bacterium is very flexible and receives a lot of genetic material. The vehicle, for example, of these multi-resistances can be viruses,” notes the CCG researcher.
Something similar happens with Staphylococcus aureus, the bacterium with which they did their second work; “There are several viruses that carry toxins that give them excessive virulence,” González Zúñiga notes of the microorganism, whose strains were obtained from samples from hospitals in Mexico City, including from the National Institute of Medical Sciences and Nutrition of Salvador Subirán.
“We have a collection of these viruses that infect various bacteria, various strains of clinical staphylococci. These are the viruses we’re working on to basically see how they infect bacteria; that is, through what mechanisms they enter. Then find out how effective they are in eliminating them.
“In the laboratory, bacteria are grown in a test tube, and when a bacteriophage is added to this bacterial culture, after a short time, within one to two hours, the number of bacteria begins to decrease. It varies greatly depending on the kind of bacteria we use, but it happens very quickly; the bacteria start to die because the phages infect them,” says González Zúñiga.
What scientists have yet to test is whether this will happen in the same way, no longer in in vitro samples, but directly in a biological system; in a mouse, for example.
“The experiment will consist of injecting a small mouse with some pathogenic bacterium, such as staphylococcus aureus, which is virulent and causing infection, and then injecting specific bacteriophages for this bacterium and killing it. I mean cure it.”
Meanwhile, the biologist shares that one of his goals is to find as many specific bacteriophages as possible for pathogenic bacteria.
“It doesn’t matter where we get them: from the soil, from livestock farms, from sewage. We study all these ecological niches in order to collect and find specific bacteriophages for staphylococci, Acinetobacter and even for Klebsiella pneumoniae,” González Zúñiga lists.
“Large research centers in North America or Europe have bacteriophage collections containing more than 10,000 viral particles that could potentially be used. This is part of our goal.”
How much do you have now?
– We are here for Rhizobium, where we have worked the most, we have over 300 of them; in the case of Staphylococcus and Acinetobacter, they should be about 20 or 30, respectively. Here the point is not only to have them, but also to know them, to characterize them.
Text and photo: Reform Agency