Stepwise pathogenic evolution of Mycobacterium abscessus.

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Most mycobacteria are environmental saprophytes, but some, like Mycobacterium tuberculosis, cause human disease.
• The emergence of Mycobacterium abscessus in cystic fibrosis (CF) patients offers insights into mycobacterial pathogenic evolution.

Purpose of the Study:

• To define generalizable steps in the pathogenic evolution of mycobacteria.
• To understand the mechanisms driving the increased pathogenicity of environmental mycobacteria in human hosts.

Main Methods:

• Analysis of the spread and evolution of Mycobacterium abscessus in the global cystic fibrosis population.
• Investigation of horizontal gene transfer and subsequent genetic mutations influencing virulence.
• Comparative analysis with Mycobacterium tuberculosis evolution.

Main Results:

• Epigenetic modifiers acquired via horizontal gene transfer drive significant increases in pathogenic potential.
• Parallel evolution in chronic lung infections leads to rapid virulence enhancement through specific gene network mutations.
• Mutations favor intracellular growth (macrophages) but reduce survival on fomites, constraining evolution with indirect transmission.

Conclusions:

• Pathogenic evolution in mycobacteria involves distinct stages, including acquisition of epigenetic modifiers and adaptation to host environments.
• Constrained evolution is observed with indirect transmission, but direct transmission (like M. tuberculosis) may accelerate adaptation.
• Early treatment and infection control are crucial to limit the spread of current and emerging mycobacterial pathogens.