A programmed cell division delay preserves genome integrity during natural genetic transformation in Streptococcus pneumoniae

Matthieu J Bergé,Christophe Grangeasse,Patrice Polard,Chryslène Mercy,Isabelle Mortier-Barrière,Yves V Brun,Michael S Vannieuwenhze,Nathalie Campo

doi:10.1038/s41467-017-01716-9

Abstract

Competence for genetic transformation is a differentiation program during which exogenous DNA is imported into the cell and integrated into the chromosome. In Streptococcus pneumoniae, competence develops transiently and synchronously in all cells during exponential phase, and is accompanied by a pause in growth. Here, we reveal that this pause is linked to the cell cycle. At least two parallel pathways impair peptidoglycan synthesis in competent cells. Single-cell analyses demonstrate that ComM, a membrane protein induced during competence, inhibits both initiation of cell division and final constriction of the cytokinetic ring. Competence also interferes with the activity of the serine/threonine kinase StkP, the central regulator of pneumococcal cell division. We further present evidence that the ComM-mediated delay in division preserves genomic integrity during transformation. We propose that cell division arrest is programmed in competent pneumococcal cells to ensure that transformation is complete before resumption of cell division, to provide this pathogen with the maximum potential for genetic diversity and adaptation.

Highlights

Competence for genetic transformation is a differentiation program during which exogenous DNA is imported into the cell and integrated into the chromosome
Since bacterial cells often have different shapes or sizes depending on their growth rate[26,27], we reasoned that if competent cells are physiologically distinct from non-competent cells, morphological differences between the two populations should be detectable
We developed a standardized method based on the Integrated Morphometric Analysis tool from Metamorph that allowed us to separate pneumococcal cells into six different classes according to progress through the cell cycle

Summary

Introduction

Competence for genetic transformation is a differentiation program during which exogenous DNA is imported into the cell and integrated into the chromosome. The SOS pathway is not universal, and many bacteria lacking a LexA homolog have evolved alternative DNA damage responses[2] Among these bacteria, the human pathogen Streptococcus pneumoniae (the pneumococcus) has been proposed to use competence for genetic transformation as a general response to stress[10,11,12]. Among the other CSP-regulated genes, those contributing to genome plasticity include the late com genes cbpD, cibA, cibB, and lytA These genes encode lytic enzymes involved in a killing mechanism, termed fratricide that can be used by competent cells to acquire DNA from non-competent pneumococci[19,20]. The cause of this growth rate reduction and its biological relevance are obscure

Methods

Results

Conclusion