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Live-Cell Forward Genetic Approach to Identify and Isolate Developmental Mutants in Chlamydia trachomatis

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Spatial constraints within the chlamydial host cell inclusion predict interrupted development and persistence.

Alexander Hoare¹, Peter Timms, Patrik M Bavoil

¹National Centre in HIV Epidemiology and Clinical Research, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. Ahoare@nchecr.unsw.edu.au

BMC Microbiology

|January 10, 2008

Summary

Chlamydia bacteria switch between inactive elementary bodies (EB) and replicating reticulate bodies (RB). A new model suggests RB detachment from host cell inclusions signals EB differentiation, impacting persistent infection. RB size is key to infection outcomes.

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Area of Science:

Microbiology
Cell Biology
Mathematical Biology

Background:

Chlamydia undergoes a developmental cycle alternating between elementary bodies (EB) and reticulate bodies (RB).
Triggers for EB-RB interchange are critical for understanding Chlamydia biology but remain unknown.

Purpose of the Study:

To propose and test a hypothesis explaining chlamydial development and differentiation.
To investigate the role of host cell contact and type three secretion (T3S) in RB replication and EB differentiation.

Main Methods:

Development of a detailed mathematical model simulating the chlamydial developmental cycle.
Incorporation of existing biological knowledge and data into the model.
Simulation of various scenarios to predict outcomes and implications.

Main Results:

The hypothesis predicts that detachment from the host cell membrane-derived inclusion, due to decreased contact via T3S injectisomes, signals RB-to-EB differentiation.
Persistent infection is an implication of the hypothesis, influenced by RB radius, T3S needle length, and inclusion number.
RB radius is the most significant determinant of persistent infection and EB yield.

Conclusions:

The model provides testable predictions for chlamydial development and persistent infection.
Relationships between RB radius, T3S needle length, and inclusion number predict infection outcomes.
Further experimental validation could significantly advance understanding of Chlamydia development.