Type 3 secretion systems - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 425

ler , thus in turn activating the LEE ( Gomez-Duarte and Kaper, 1995 ). Inter-
estingly, the EAF plasmid is not present in EHEC strains, which still show
LEE transcription; nonetheless, EHEC strains do possess PerC homologs in
bacteriophage-acquired islands, several of which have been shown to induce
LEE transcription ( Iyoda and Watanabe, 2004 ; Porter et al., 2005 ).
In addition to ler , two other regulatory genes, grlR and grlA , have been iden-
tified in the LEE ( Figure 14.1 A). Both genes are activated by ler , but appear to
have contradictory effects: GrlA is a LEE activator, forming a positive-feedback
loop with ler, while GrlR binds to GrlA and prevents its function ( Barba et al.,
2005 ; Iyoda et al., 2006 ).
Of note, even though it is not yet established if the ETT2 system is func-
tional, three regulatory genes have been identified for this system ( Figure
14.1 C). The eilA gene is homologous to the Salmonella SPI-1 T3SS regulator
hilA ( Ellermeier and Slauch, 2007 ), and its overexpression does induce tran-
scription of ETT2 genes ( Sheikh et al., 2006 ). In addition, the two regulatory
genes etrA and eivF encoded by the ETT2 T3SS show a dramatic inhibitory
effect on transcription of the LEE genes ( Zhang et al., 2004 ), revealing a strik-
ing cross talk between T3SSs.
Regulation of the Mxi/Spa system
The Shigella flexneri T3SS possesses a regulatory gene, virB ( Figure 14.1 B), show-
ing similarity to the LEE ler . Indeed, VirB was shown to function via a similar
mechanism of displacing the H-NS repressor ( Tobe et al., 1993 ). However, a second
regulatory gene, virF , located 30 kb away from the T3SS locus, is required for the
activation of virB ( Adler et al., 1989 ). VirF belongs to the AraC family of transcrip-
tion factors, but acts similarly to Ler or VirB, by displacing the H-NS repressor. It
has been proposed that this dual regulatory pathway allows for a tighter control of
transcriptional levels under changing conditions ( Porter and Dorman, 1997 ).
A second regulatory gene, mxiE , has been identified in the T3SS locus ( Kane
et al., 2002 ), which promotes specifically the transcription of six effector pro-
teins, but not of components of the secretion apparatus or injectisome. Interest-
ingly, the protein MxiE also belongs to the AraC family of transcription factors,
but acts through a different mechanism. Indeed, MxiE is not sufficient to acti-
vate transcription, but requires a direct binding to the effector chaperone IpgC
( Mavris et al., 2002 ). It has been argued that the presence of free IpgC protein in
the bacterial cytosol is used as a signal that the secretion apparatus is active, thus
preventing the unnecessary transcription of effectors during apparatus assembly.
CONCLUSION
Since the discovery of type 3 secretion nearly 20 years ago, significant progress
has been made towards understanding the detailed molecular mechanisms by
which this process is performed, albeit with structural and mechanistic analysis