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Surrogate models in pathogenic Mycobacterium research: a systematic review.
Marta Nerini1, Anisa Ribani2, Stefania Papa3
1Department of Biology, University of Florence, Sesto Fiorentino, Florence, 50019, Italy.
Journal of Applied Microbiology
|October 25, 2025
Summary
Safe Mycobacterium surrogates enable research in lower biosafety labs, advancing drug and vaccine development. Mycobacterium smegmatis is a common choice, though environmental studies and drug screening need further exploration.
Area of Science:
- Microbiology
- Public Health
- Biotechnology
Background:
- Pathogenic Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium bovis, necessitate Biosafety Level 3 (BSL-3) containment, restricting accessibility for research.
- Safe and effective surrogate models are essential for conducting studies in lower biosafety settings (BSL-1/2), thereby facilitating progress in public health initiatives.
Purpose of the Study:
- To review existing literature utilizing the term 'surrogate' in relation to mycobacteria.
- To identify effective mycobacterial surrogate models and pinpoint research gaps.
- To categorize research areas where surrogates have been applied.
Main Methods:
- A systematic review of studies employing mycobacterial surrogates was conducted.
- Research topics were categorized based on study objectives.
- The frequency and application of different surrogate species were analyzed.
Main Results:
- Mycobacterium smegmatis is the most frequently used surrogate due to its non-pathogenic nature, rapid growth, and genetic tractability.
- Mycobacterium marinum (BSL-2) aids in understanding virulence and stress responses, while Mycobacterium bovis BCG is used in vaccine and drug studies.
- Research predominantly focuses on mycobacterial physiology and chemical control, with environmental studies being significantly underrepresented.
Conclusions:
- Mycobacterial surrogate models facilitate safer, cost-effective research in BSL-1/2 environments, supporting the development of drugs, vaccines, and diagnostics.
- Limitations exist, particularly in drug screening efficacy with M. smegmatis and the lack of environmental research.
- Expanding ecological studies and refining surrogate model selection are crucial for enhancing control strategies against pathogenic mycobacteria.
