|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
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
The second is the processing
of transforming DNA. We have characterized the polarity and the kinetics
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
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 :
regulation, DNA processing, DprA, genetic transformation, RecA, SOS, virulence
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;
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
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the origin and dynamics of the
RUP element in Streptococcus pneumoniae.