Replication-dependent size reduction precedes differentiation in Chlamydia trachomatis

Jennifer K Lee,Christopher N Chander,Christine Sütterlin,Tracy H Lou,Sean S Pairawan,Melody C Guo,Frederic Y M Wan,Mark H Ellisman,Germán A Enciso,Ming Tan,Daniela Boassa

doi:10.1038/s41467-017-02432-0

Abstract

Chlamydiatrachomatis is the most common cause of bacterial sexually transmitted infection. It produces an unusual intracellular infection in which a vegetative form, called the reticulate body (RB), replicates and then converts into an elementary body (EB), which is the infectious form. Here we use quantitative three-dimensional electron microscopy (3D EM) to show that C. trachomatis RBs divide by binary fission and undergo a sixfold reduction in size as the population expands. Conversion only occurs after at least six rounds of replication, and correlates with smaller RB size. These results suggest that RBs only convert into EBs below a size threshold, reached by repeatedly dividing before doubling in size. A stochastic mathematical model shows how replication-dependent RB size reduction produces delayed and asynchronous conversion, which are hallmarks of the Chlamydia developmental cycle. Our findings support a model in which RB size controls the timing of RB-to-EB conversion without the need for an external signal.

Highlights

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection
We identified a conversion intermediate called the intermediate body (IB), which has a target-like appearance from DNA condensation beginning in its center[7]
An elementary body (EB) was analyzed in 6–7 consecutive EM sections, while an reticulate body (RB) was examined in 11–21 EM sections

Summary

Introduction

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection. It produces an unusual intracellular infection in which a vegetative form, called the reticulate body (RB), replicates and converts into an elementary body (EB), which is the infectious form. A stochastic mathematical model shows how replication-dependent RB size reduction produces delayed and asynchronous conversion, which are hallmarks of the Chlamydia developmental cycle. Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection and accounts for 60% of all infectious disease cases reported to the CDC1. RB-to-EB conversion is first detected at about 24 h.p.i. and occurs asynchronously This unusual developmental cycle ends at 40–48 h.p.i. with release of EBs to infect new host cells. Upon re-examination, we have noted that these electron micrographs reveal that the first few RBs in an inclusion are generally larger than the RB population at later times, this difference has not been remarked upon

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Conclusion