Bacteriophages have restored the sensitivity of bacteria to antibiotics
Antibiotic-resistant Acinetobacter baumannii bacteria acquired antibiotic sensitivity after treatment with bacteriophages. It was found that in an attempt to escape the bacteriophages, the bacteria mutated in such a way that they became susceptible to antibiotics once again.
The resistance of pathogenic bacteria to antibiotics is one of the most serious problems in modern healthcare. Doctors most frequently encounter severe antibiotic-resistant infections caused by representatives of bacterial species such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. (collectively referred to as ESKAPE). The development of new antibiotics capable of dealing with these “superbugs” is progressing very slowly; therefore, scientists are actively searching for alternative methods of antibiotic therapy. One of the most well-studied and accessible methods today is bacteriophages.
Scientists at Monash University in Melbourne investigated the effects of various bacteriophages on antibiotic-resistant strains of A. baumannii and isolated two bacteriophages specific to this bacterium—ΦFG02 and ΦCO01. During the experiment, however, it was discovered that some of the A. baumannii strains were resistant to bacteriophages. The reason for the phage resistance turned out to be a mutation that deprived the bacteria of the surface capsule to which the phages actually attached before entering the bacterial cell. In the absence of a capsule, phages cannot attach to or infect the bacteria. However, this same capsule is a barrier to various antibiotics, and thanks to it, A. baumannii is insensitive to therapy with most antibiotics. By mutating to protect themselves against bacteriophages, the bacteria therefore become sensitive to antibiotics again. Experiments showed that in the presence of the ΦFG02 phage, the bacterium became 16 times more sensitive to ceftazidime and 2 times more sensitive to other beta-lactams and ciprofloxacin. Furthermore, the ΦCO01 phage restored the sensitivity of A. baumannii to minocycline, cefepime, and ampicillin.
Another interesting effect of phages was discovered: mutant bacteria began to succumb to the action of the complement system (an element of the non-specific immune response in mammals). For this reason, in experiments on mice infected with phage-resistant strains of A. baumannii, infection with bacteriophages led to a reduction in the number of bacteria in the affected tissues after 8 to 12 hours: by one order of magnitude in the presence of ΦFG02 and by two orders of magnitude in the presence of ΦCO01. That is, bacteriophages made the bacterium more vulnerable to the immune defenses of the mouse organism.
Translation of the source:
* Gordillo Altamirano F., Forsyth J. H., Patwa R. et al. Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials. Nat Microbiol, Published: January 11, 2021.
https://doi.org/10.1038/s41564-020-00830-7
