A specific secretion system mediates PPE41 transport in pathogenic mycobacteria

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Mycobacterial genomes feature expanded PE and PPE gene families, particularly in pathogenic species.
• PPE41 protein secretion by pathogenic mycobacteria occurs in vitro and within host macrophages.
• The absence of a signal sequence in PPE41 suggests a specialized secretion mechanism.

Purpose of the Study:

• To identify the secretion system responsible for PPE41 protein transport in pathogenic mycobacteria.
• To investigate the role of the ESX-5 secretion system in PPE41 secretion and mycobacterial virulence.

Main Methods:

• Identification of a gene in Mycobacterium marinum affecting PPE41 secretion.
• Analysis of the ESX-5 gene cluster and its components.
• Heterologous expression of ESX-5 components in Mycobacterium smegmatis.
• Assessment of an ESX-5 mutant's virulence in M. marinum.

Main Results:

• A gene mutation in M. marinum significantly reduced PPE41 secretion.
• The identified gene is part of the conserved ESX-5 secretion system.
• Complete ESX-5 locus introduction in M. smegmatis enabled PPE41 secretion.
• The ESX-5 mutant of M. marinum exhibited impaired spreading to uninfected macrophages.

Conclusions:

• The ESX-5 secretion system is essential for PPE41 protein secretion in pathogenic mycobacteria.
• ESX-5 plays a significant role in the virulence and intercellular spread of mycobacteria.