It is known that secondary metabolites of some bacteria are antibiotics, meaning they can exert antibacterial activity. However, they can also have antiviral properties, specifically by inhibiting bacteriophages. For example, it has been shown that the proliferation of bacteriophages specific to bacteria of the genus Streptomyces can be inhibited by aminoglycoside antibiotics*.

Aminoglycosides (neomycin, kanamycin, gentamicin, tobramycin, amikacin, arbekacin, apramycin, plazomicin, etc.) are natural and semisynthetic antibiotics derived from soil bacteria of the actinomycete family, particularly those of the genus Streptomyces. They were among the first antibiotics to enter routine clinical practice in the mid-20th century. They were widely used as first-line agents, but gradually lost popularity due to the adoption of less toxic, broader-spectrum antibiotics. Recently, there has been a resurgence of interest in these drugs: new effective agents have been introduced, as well as combinations of aminoglycosides with other antibiotics, which, due to their synergistic action, are effective against multidrug-resistant bacterial strains.

Aminoglycoside antibiotics were also found to inhibit some bacteriophages. In the experiment, specific bacteriophages were added to cultures of Streptomyces bacteria, after which aminoglycoside antibiotics were also added to some of the cultures. The results were as follows: in the absence of aminoglycosides, phage plaque formation was observed, whereas in the presence of aminoglycosides, plaques were absent. Therefore, aminoglycosides inhibited phage infection. A wide range of gram-positive and gram-negative host bacteria and bacteriophages were used in the experiment.

Similar experiments were conducted on bacterial cultures in liquid media. The addition of phages significantly reduced bacterial concentrations. However, subsequent addition of aminoglycosides resulted in restoration of normal bacterial growth and an increase in bacterial concentrations.

Inhibition of phage infection was also observed when they were added to the culture medium in which streptomycetes, producers of the aminoglycoside antibiotic apramycin, grew.

A study of apramycin's mechanism of action against bacteriophages revealed that the antibiotic does not affect the stages of phage adsorption to the bacterial surface or the injection of phage DNA into the bacterium. Using quantitative PCR, changes in phage DNA concentration were measured during the bacterial replication cycle. It was found that although the amount of phage DNA increases exponentially overall with the addition of apramycin, this begins earlier than without the antibiotic and then reaches its lowest values. A study of transcriptional profiles throughout phage infection using complete phage genome sequencing revealed that apramycin inhibits the replication and transcription of phage genes. These findings were confirmed using fluorescence microscopy. Thus, aminoglycosides inhibit phages by directly interfering with their life cycle.

Therefore, during clinical trials, phage preparations must be tested for sensitivity to aminoglycosides. However, aminoglycosides are only one type of antiphage compound, and the search for more must continue, as they negatively impact the results of phage therapy.

* Perry S. Molecular multitasking: inhibition of phage infection by aminoglycoside antibiotics. Capsid & Tail, 2021; 156 https://phage.directory/capsid/phage-inhibition-by-aminoglycoside-antibiotics