ESAT-6-like protein secretion in Bacillus anthracis

Area of Science:

• Microbiology
• Molecular Biology
• Bacterial Pathogenesis

Background:

• Type VII secretion systems (T7SS) are critical for bacterial virulence.
• WXG100 proteins are characteristic substrates of T7SS.
• Bacillus anthracis utilizes T7SS for secreting effector proteins.

Purpose of the Study:

• To investigate the secretion mechanism of WXG100 proteins in Bacillus anthracis.
• To identify the role of EsxB in the secretion of other WXG100 substrates.
• To determine the structural requirements for EsxB secretion and function.

Main Methods:

• Bacterial culture and protein secretion analysis.
• Genetic manipulation of Bacillus anthracis strains.
• Protein interaction studies and mutational analysis of EsxB.
• Immunological assays in infected animal models.

Main Results:

• Bacillus anthracis secretes EsxB and EsxW via T7SS.
• EsxB is essential for EsxW secretion, but EsxW is not required for EsxB secretion.
• N- or C-terminal modifications of EsxB did not abolish its secretion or ability to secrete EsxW.
• Ubiquitin insertion into the central turn of EsxB abrogated secretion.
• Humoral immune responses in infected guinea pigs indicate T7SS activation during infection.

Conclusions:

• EsxB acts as a key facilitator for the secretion of EsxW through the T7SS.
• The central turn region of EsxB is critical for its secretion and function.
• The Bacillus anthracis type VII secretion pathway is active during infection, suggesting a role in pathogenesis.