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B. Colonna - Deciphering the complexity of the virulence networks in Shigella and enteroinvasive Escherichia coli (EIEC)
undergo a series of convergent mutations in genes
which negatively interfere with the expression or
function of virulence factors required for the survival
within the host. The case of the cad system
exemplifies one of the most important mutations
arising by loss of antivirulence genes in Shigella.
The cad operon encodes one of the main decarboxylase
system based on the activity of lysine decarboxylase
and is crucial for the maintenance of pH
levels suitable for cell survival. Despite the fact that
the cad system may be important during the bacterial
transit through the intestinal tract, in Shigella
and EIEC such a system has been completely lost.
By comparative analysis of molecular rearrangements
inducing silencing of the cad operon we have
observed that the lack of lysine decarboxylase activity
has been attained through diverse strategies, and
that the first silencing step of the cad locus might
have been the inactivation of the cadC gene, followed
by a spread of insertion sequences in cadB
and cadA inducing deletions within the cad locus or
extending to the flanking regions. The observed
lack or inactivation of the cadC gene can be accounted
for by considering that CadC, the regulator of
the cadBA operon, might play additional roles in
controlling cellular functions not directly related to
lysine utilization. In order to understand whether
the CadC regulator may play a direct or indirect role
in the control of other genes involved in the adaptation
of the bacterium to the host environment we
investigated how the expression profile of E. coli has
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been affected by the disappearance of CadC.
Transcriptome analysis revealed that several genes
where over-expressed in the absence of CadC,
including genes encoding other systems involved in
pH homoestasis like the acid stress response or the
arginine /putrescine trasport systems.
Since both, the loss and the acquisition of new
genetic systems, are flanked by the arrival or by the
lack of transcriptional regulators, we plan to further
investigate on how the transcriptional profile of the
ancestor cell has been modified in order to improve
survival within the host tissues.
Selected publications
Prosseda G, Latella MC, Barbagallo M, Nicoletti
M, Al Kassas R, Casalino M, Colonna B. The two
faced role of the cad genes in the virulence of pathogenic
Escherichia coli. Res Microbiol. 2007, 158:487-
93.
Prosseda G, Casalino M, Colonna B. Regulation of
virulence genes in Shigella hovers between gain and
loss of transcriptioanl activators. Nova Acta
Leopoldina 2008, 98:65-70.
Roscetto E, Rocco F, Carlomagno MS, Casalino M,
Colonna B, Zarrilli R, Di Nocera PP. PCR-based
rapid genotyping of Stenotrophomonas maltophilia
isolates. BMC Microbiol. 2008, 8:202-7.