Diminished LcrV secretion attenuates Yersinia pseudotuberculosis virulence

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Type III secretion systems (T3SS) are critical for gram-negative bacterial virulence, delivering effector proteins into host cells.
• T3SS substrates include antihost effectors and translocators, with N-terminal signals mediating recognition by the secretion machinery.
• LcrV, a T3SS translocator, has known roles in translocation, regulation, and immunomodulation.

Purpose of the Study:

• To investigate the significance of LcrV exterior targeting for its regulatory, effector targeting, and virulence functions.
• To identify key amino acids in LcrV essential for its secretion.
• To differentiate the roles of LcrV in regulation versus effector translocation and virulence.

Main Methods:

• Analysis of N-terminal amino acid importance for LcrV secretion.
• In vitro cell infection assays to assess effector translocation.
• Murine infection models to evaluate LcrV's role in systemic virulence.

Main Results:

• Specific N-terminal amino acids were identified as critical for LcrV secretion.
• Low levels of exported LcrV sufficed for in vitro effector translocation.
• Complete LcrV export was necessary for virulence in a systemic murine infection model.

Conclusions:

• The study dissects LcrV's functions, separating its role in regulation from its role in effector targeting and virulence.
• Efficient LcrV export is a prerequisite for bacterial virulence, highlighting its importance beyond simple translocation.
• Understanding LcrV secretion provides insights into T3SS-mediated pathogenesis.