Abstract Background Mycobacterium abscessus is a rapidly growing nontuberculous mycobacteria that displays extensive multidrug resistance, making it exceptionally difficult to treat and associated with poor clinical outcomes. The renewed focus on bacteriophage therapy has brought Mycobacterium-specific phages to the forefront as a promising alternative, especially for infections unresponsive to conventional antibiotics. Yet, their inherently narrow host range poses a major obstacle, underscoring the ongoing need to discover novel phages to effectively target local clinically significant M. abscessus isolates. Materials and Methods We launched a mycobacteriophage detection by isolating candidate phages from wastewater. These newly obtained phages were evaluated for their lytic activity against multiple drug-resistant Mycobacterium abscessus isolates. Furthermore, their therapeutic potential was examined in an M. abscessus-infected THP-1 macrophage model, providing functional insights into their intracellular antibacterial efficacy. Results We had isolated and characterized two novel mycobacteriophages capable of infecting and lysing clinical Mycobacterium abscessus isolates. Cryo-electron microscopy (cryo-EM) analysis provided high-resolution visualization of their structural organization. In parallel, we are establishing an adaptive training strategy to enhance phage-host compatibility and boost bactericidal efficiency against diverse clinical M. abscessus strains. In a THP-1 macrophage infection model, these phages markedly reduced intracellular M. abscessus loads, underscoring their strong therapeutic potential for combating drug-resistant infections. Conclusions Mycobacteriophages can be selectively isolated and adapted to target Mycobacterium abscessus, demonstrating efficacy in macrophage infection models. These findings highlight their potential as an alternative therapeutic approach for difficult M. abscessus infection. This abstract is funded by: Academia Sinica
Shu et al. (Fri,) studied this question.