Tight Interplay between Replication Stress and Competence Induction in Streptococcus pneumoniae.

Vanessa Khemici,Marc Prudhomme,Patrice Polard

doi:10.3390/cells10081938

Abstract

Cells respond to genome damage by inducing restorative programs, typified by the SOS response of Escherichia coli. Streptococcus pneumoniae (the pneumococcus), with no equivalent to the SOS system, induces the genetic program of competence in response to many types of stress, including genotoxic drugs. The pneumococcal competence regulon is controlled by the origin-proximal, auto-inducible comCDE operon. It was previously proposed that replication stress induces competence through continued initiation of replication in cells with arrested forks, thereby increasing the relative comCDE gene dosage and expression and accelerating the onset of competence. We have further investigated competence induction by genome stress. We find that absence of RecA recombinase stimulates competence induction, in contrast to SOS response, and that double-strand break repair (RexB) and gap repair (RecO, RecR) initiation effectors confer a similar effect, implying that recombinational repair removes competence induction signals. Failure of replication forks provoked by titrating PolC polymerase with the base analogue HPUra, over-supplying DnaA initiator, or under-supplying DnaE polymerase or DnaC helicase stimulated competence induction. This induction was not correlated with concurrent changes in origin-proximal gene dosage. Our results point to arrested and unrepaired replication forks, rather than increased comCDE dosage, as a basic trigger of pneumococcal competence.

Highlights

All genomes are susceptible to potentially life-threatening damage, of both environmental and endogenous origin
The SOS system is widespread in bacteria but not universal, and some species have evolved other responses to genome damage [3]
Light emitted by the growing cells is recorded in real time as relative luminescence units (RLU) normalized to cell density expressed as OD492

Summary

Introduction

All genomes are susceptible to potentially life-threatening damage, of both environmental and endogenous origin To confront this challenge to their survival, organisms have evolved a range of repair pathways, notably those inducible by the damage itself. Competence provides the cells with new properties, including the well-known horizontal gene transfer process of genetic transformation [5]. Many species share this ability to convert to competence for transformation, as well as a similarity of mechanism in the importing of external DNA across the cell membrane and integration into the genome by RecA-directed

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