Bacterial secretion and the role of diffusive and subdiffusive first passage processes

Area of Science:

• Microbiology
• Biophysics
• Computational Biology

Background:

• Bacteria utilize type III secretion systems (T3SS) to inject effector proteins into host cells.
• The precise spatio-temporal mechanisms of T3SS-mediated infection are not fully understood.
• Challenges in tracking single molecules within cells limit theoretical predictions of secretion timing.

Purpose of the Study:

• To develop a model quantifying effector protein transport time to T3SS needle complexes.
• To investigate the influence of intracellular transport characteristics on secretion dynamics.
• To explore the role of translocators in activating needle complexes.

Main Methods:

• Development of a mathematical model for protein effector transport within bacterial cytoplasm.
• Utilizing kinetic parameters from Shigella flexneri for model validation.
• Simulating effector protein movement to predict time to reach needle complexes.

Main Results:

• The model quantifies the time required for protein effectors to reach needle complexes based on cytoplasmic transport.
• It highlights the dependence of secretion timing on intracellular diffusion and active transport.
• The model provides semi-quantitative explanations for experimental observations regarding translocator function.

Conclusions:

• Understanding intracellular transport is crucial for predicting type III secretion kinetics.
• The model offers insights into the activation mechanisms of needle complexes by translocators.
• This work bridges theoretical modeling with experimental observations in bacterial pathogenesis.