The authors of the study, the results of which were published* in the journal Disease Models & Mechanisms, proposed a new model for finding optimal combinations of phages and antimicrobial agents in the treatment of infections caused by antibiotic-resistant bacteria.

Mycobacterium abscessus is a pathogenic bacterium that causes severe lung diseases, which respond to antibiotics in only about half of cases. Bacteriophages are promising agents for treating antimicrobial-resistant infections. Scientists from the Centenary Institute at the University of Sydney (Australia) used zebrafish as models to study the effectiveness of phage therapy and select the optimal combination of phages and antibiotics for the treatment of mycobacterial infections.

What is the advantage of zebrafish as model organisms? Zebrafish embryos are transparent during the early stages of development, so using fluorescent bacteria and transgenic zebrafish lines with fluorescent macrophages allows for observation of the bacteria's interactions with the host organism. Furthermore, the innate immunity of zebrafish embryos is fully functional 30 hours after fertilization (adaptive immunity matures over several weeks after fertilization, when the embryo is no longer transparent and its reactions are difficult to observe). Studies on zebrafish embryos have shown that phage therapy can only be successful if the innate immune system is functioning normally.

In experiments using the proposed model, the scientists demonstrated that the Muddy bacteriophage effectively lyses M. abscessus GD01 and increases embryo survival. According to the authors, zebrafish can be used for preclinical evaluation of new phage preparations, as well as combinations of phage preparations and antibiotics, prior to use in humans.

* Johansen MD, Alcaraz M, Dedrick RM, Roquet-Banères F et al. Mycobacteriophage–antibiotic therapy promotes enhanced clearance of drug-resistant Mycobacterium abscessus. Dis. Model. Mech., 2021; 14: dmm049159. https://doi.org/10.1242/dmm.049159