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Pneumococcal transformation

 



Figure 1: Regulation of competence development in S. pneumoniae. Color code: red, peptide signaling; blue arrows, transcriptional activation. The competence pheromone (CSP) is an unmodified peptide encoded by the comC gene. It is matured and exported by ComA-ComB. The CSP acts extracellularly to stimulate the histidine kinase membrane receptor, ComD, which autophosphorylates and donates a phosphate to its cognate response regulator ComE. ComE~P then activates directly the expression of the comX gene, which encodes an alternative sigma factor required for the specific expression of late competence (com) genes. The latter include genes encoding proteins involved in DNA uptake (Fig. 2) and processing (Fig. 3). Kinetic analyses of CSP-induced transcription revealed that the early com genes are first induced strongly (e.g. comDE probe), but briefly (about 5 min). Then, while their transcription is rapidly shutoff, induction of the late com genes occurs (e.g. recA probe) (11).

Streptococcus pneumoniae is a Gram positive bacterium of low GC content, pathogenic for man. We are interested in the genetic transformation (16, 18) of this species from two points of view.
The first is the role(s) of competence for transformation in the biology of S. pneumoniae. We are approaching this question by i) investigating the regulation of competence development, ii) looking for signal(s) which trigger the development of competence, and iii) examining the changes in cell physiology that accompany competence induction (e.g. sensitization to autolysis).
The second is the processing of transforming DNA. We have characterized the polarity and the kinetics of DNA uptake, and have identified the steps affected in several mutants of the DNA transport apparatus (17). We are now studying the role of two competence-induced proteins, DprA and RecA, in the protection of incoming ssDNA (19) and its final processing into recombination products.
Examination of parameters affecting recombination in S. pneumoniae suggested that many of them have been optimised during evolution to favor genetic exchanges by transformation (13), including through the capture of foreign DNA (15). This bacterium could thus use transformation to adapt to its host and bypass host defences. Our recent findings that the competence regulon contains more than one hundred genes (20), only a fraction of which are required for transformation, and that competence-dependent autolysis (20) can lead to the release of virulence factors (in preparation) suggest that competence might not only enhance genetic plasticity but also contribute directly to the pathogenicity of S. pneumoniae.

Organism studied :

Streptococcus pneumoniae.

Keywords :

competence regulation, DNA processing, DprA, genetic transformation, RecA, SOS, virulence

Grants:

Research in the lab is funded in part by the European Union (October 2000-April 2004; grant QLK2-CT-2000-00543) and the Ministère délégué à la Recherche et aux Nouvelles Technologies (ACI Microbiology grant; awarded in June 2003). Miriam Moscoso (20, 17, 21) was the recipient of a Marie-Curie Individual Fellowship (October 2000-2002; QLK2-CT-1999-51509).

Part of the team's work is supported by the European Community's Seventh Framework Programme FP7/2007-2013 under Grant Agreement No. HEALTH-F3-2009-222983 (Pneumopath project). For a project description, see website at http://www2.le.ac.uk/projects/pneumopath

Links to previous investigations:

- A new family of high affinity ABC manganese and zinc permeases.
- Repeated extragenic sequences in procaryotic genomes: a proposal for the origin and dynamics of the RUP element in Streptococcus pneumoniae
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Univ.Toulouse
Fédération de Recherche
 

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Laboratoire de Microbiologie
et Génétique Moléculaires
UMR 5100