Cancellation of resistance
An attempt to protect themselves from bacteriophages returned the bacteria sensitivity to antibiotics
Polina Loseva, N+1
Australian scientists used bacteriophage viruses against the antibiotic-resistant bacterium Acinetobacter baumannii. Bacteriophages use the protective capsule of the bacterium to attach and penetrate inside the cell, and researchers have found that when in their presence bacteria acquire mutations that deprive them of the capsule, they become vulnerable to antibiotics.
The work was published in the journal Nature Microbiology (Altamirano et al., Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials).
Despite the fact that a variety of bacteria can become a super-microbe resistant to the action of many antibiotics (for example, in 2019, a strain of salmonella from Congo), most often these are representatives of six species that are united in the abbreviation ESKAPE: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp.
Theoretically, there may be several options to cope with them – for example, you can look for new antibiotics that do not cause resistance, build artificial antimicrobial molecules. There is another option – to fight bacteria with the help of bacteriophage viruses (you can genetically modify them so that they will surely hit the target).
A group of scientists from Monash University in Melbourne, led by Jeremy Barr, was searching for bacteriophages that would infect the bacterium Acinetobacter baumannii, one of the six ESKAPE. They picked up two phages, ΦFG02 and ΦCO01, which have the ability to parasitize different strains of bacteria. But among the bacterial cultures, mutants resistant to bacteriophages were also found – and the researchers noticed an unexpected feature in them: they turned out to be devoid of a polysaccharide capsule.
Two strains of the bacterium: wild type (left) and "naked", without a capsule (right). Figure from the article by Altamirano et al.
Having tracked the distribution of bacteriophages in bacterial culture, the authors found out that the viruses ΦFG02 and ΦCO01 do not attach well to mutants – at least 99 and 97 percent, respectively, were found on the surface of wild-type bacteria. Consequently, the capsule usually helps viruses to get inside, and "naked" bacteria are impregnable.
However, the same capsule serves as a barrier to many antibiotics to which Acinetobacter baumannii is resistant. Therefore, the researchers assumed that by acquiring protection from phages, mutants would become vulnerable to antibiotics. Indeed, in the presence of the phage ΦFG02, the bacterium became 16 times more sensitive to ceftazidime and 2 times more sensitive to other beta-lactams and ciprofloxacin. And the phage ΦCO01 gave her sensitivity to minocycline, cefepem and ampicillin. In addition, the proximity to phages led to the fact that mutants began to succumb to the action of complement – a system of proteins from human blood, which begins to drill holes in the shells of bacteria even before immune cells recognize it as an enemy.
Finally, the authors demonstrated that phages can also be effective in vivo. To do this, mice were infected with the bacterium, and after, they were introduced into the places of infection of bacteriophages. As a result, after only 8-12 hours, the number of bacteria in the affected tissues decreased by an order of magnitude in the presence of ΦFG02 and by two orders of magnitude in the presence of ΦCO01. Thus, even without the participation of antibiotics, bacteriophages made the bacterium more vulnerable to the mouse body's own defenses.
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