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Updated: Mar 13, 2026
Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
Smooth-to-rough morphotype switching, a mechanism of phage resistance in Mycobacterium abscessus
Jun Hao Liew1,2, Ayuni Norman1,2, Morgane Illouz3
1A*STAR Infectious Diseases Labs, Agency for Science, Technology and Research, 8A Biomedical Grove, Immunos #05-13, Singapore 138648, Singapore.
Abstract:
Mycobacterium abscessus infections represent a growing global health concern due to their severe pathology and difficulty of treatment, largely driven by their intrinsic antimicrobial resistance. While phage therapy has emerged as a promising alternative approach, studies have predominantly focused on glycopeptidolipids (GPL)-deficient M. abscessus rough variants instead of the GPL-producing smooth variants predominant in Asia. Here, we aim to develop phage cocktails targeting both smooth and rough morphotypes. In the process, we found that phage treatment of smooth variants can select for rough morphotype switching from smooth-to-rough variants in vitro and in vivo, resulting in phage resistance associated with mutations within the GPL biosynthetic locus. We validated our findings in vitro and in vivo, suggesting a two-layered phage combination that surpasses single-phage treatments and potentially improves clinical phage cocktail strategies. This work underlines the need to better understand mechanisms of phage resistance in phage therapy and associated potential adverse effects and solutions. Phage resistance in M. abscessus through morphotype switching is clinically significant, as it may complicate treatment outcomes but could be averted with proper phage combinations.
Insights
Mycobacterium abscessus infections are hard to treat. Phage therapy can cause resistance by switching morphotypes, but combination phage treatments may overcome this.
Area of Science:
- Microbiology
- Bacteriology
- Antimicrobial Resistance
Background:
- Mycobacterium abscessus infections pose a significant global health challenge due to treatment difficulties and intrinsic antimicrobial resistance.
- Phage therapy is a potential alternative, but research often overlooks smooth variants prevalent in Asia, focusing instead on rough variants.
Purpose of the Study:
- To develop phage cocktails effective against both smooth and rough morphotypes of Mycobacterium abscessus.
- To investigate morphotype switching as a mechanism of phage resistance in M. abscessus.
Main Methods:
- Development of phage cocktails targeting smooth and rough M. abscessus variants.
- In vitro and in vivo experiments to assess phage treatment efficacy and resistance mechanisms.
- Genomic analysis to identify mutations associated with phage resistance.
Main Results:
- Phage treatment of smooth M. abscessus variants selected for a switch to the rough morphotype, conferring phage resistance.
- This smooth-to-rough morphotype switching was linked to mutations in the glycopeptidolipid (GPL) biosynthetic locus.
- A two-layered phage combination demonstrated superior efficacy compared to single-phage treatments.
Conclusions:
- Morphotype switching is a clinically significant mechanism of phage resistance in M. abscessus.
- Understanding and addressing this resistance mechanism is crucial for effective phage therapy.
- Combination phage strategies, potentially targeting both morphotypes, may improve clinical outcomes and avert resistance development.
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