Locus of Enterocyte Effacement: A Pathogenicity Island Involved in the Virulence of Enteropathogenic and Enterohemorragic Escherichia coli Subjected to a Complex Network of Gene Regulation

Table 1

Regulators involved in LEE genes transcription.

Regulator	Bacteria	Regulatory mechanism	Phenotype/response	References
LEE-encoded
GrlA	C. rodentium; EPEC, EHEC	Binding LEE1 promoter	Activates LEE expression through Ler	Deng et al., 2004 [30]
GrlR	C. rodentium; EPEC, EHEC	Binding to GrlA preventing it to bind LEE-1 promoter	Represses Ler/LEE expression	Deng et al., 2004 [30]
Ler	A/E pathogens	Binding to LEE promoters	Activates expression of all LEE operons	Elliott et al., 2000 [13]
Non-LEE encoded
BipA	EPEC, EHEC	Activates ler transcription	Activates LEE expression through Ler	Grant et al., 2003 [46]
Cpx	EPEC, EHEC	Downregulates LEE4 and LEE-5 transcription	Represses LEE expression	Macritchie et al., 2008 [51]
Fis	EPEC	Activates ler and LEE4 transcription	Activates LEE expression	Goldberg et al., 2001 [45]
GadE	EHEC		Represses LEE expression	Vanaja et al., 2009 [50]
Hha	EHEC	Binding ler promoter	Represses Ler transcription	Sharma and Zuerner, 2004 [48]
H-NS	EPEC, EHEC	Binding to LEE1, LEE2, LEE3 and LEE5 regulatory region	Represses Ler expression	Bustamante et al., 2001 [28]
IHF	EPEC	Binding upstream to ler promoter	Activates ler, orf3, orf5, and orf2 expression	Friedberg et al., 1999 [26]
Pch/PerC 1, 2^*, 3^*	EHEC	Enhancing ler transcription	Activates LEE expression; ^*represses LEE1 transcription	Iyoda and Watanabe, 2004, [44]; Porter et al., 2005 [38]
PerC	Typical EPEC	Activating LEE1 promoter	Activates LEE expression	Mellies et al., 1999 [11]
RgdR	EHEC	Activating LEE1 transcription	Activates LEE expression	Flockhart et al., 2012 [47]
RpoN	EHEC	Activating grlA, repressing gadE	Activates LEE expression	Riordan et al., 2010 [49]
SspA	EHEC	Repressing H-NS expression	Activates LEE expression	Goldberg et al., 2001 [45]
FusK/R	EHEC	Represses LEE1	Represses LEE expression	Pacheco et al., 2012 [68]
EutR	EHEC	Activates LEE1	Activates LEE expression	Kendall et al., 2012 [69]
LeuO	EHEC	Activates LEE1	Activates LEE expression	Takao et al., 2014 [67]
SdiA	EHEC	represses LEE1	represses LEE expression	Sheng et al., 2013 [74]
Posttranscriptional
ClpXP	EHEC	Regulating intracellular protein levels of GrlR and; RpoS	Positively regulates LEE expression	Tomoyasu et al., 2005 [56]; Iyoda and Watanabe, 2005 [37]
CsrA	EPEC	Binding to the leader segment of the sepL  espADB mRNA and enhancing the steady-state transcript and protein levels	Positively regulates LEE expression	Bhatt et al., 2009 [55]
DegP	EPEC	Protease and chaperone activity	Represses LEE expression	Macritchie et al., 2012 [52]
DsrA	EHEC	Affecting the levels of functional transcripts of ler	Activates LEE expression	Laaberki et al., 2006 [58]
Hfq	EHEC	Acting in ler and grlRA mRNA	Activates or represses LEE expression, depending on the strain background	Shakhnovich et al., 2009 [63]; Hansen and Kaper, 2009 [64]; Kendall et al., 2011 [65]
RNaseE	EHEC	Splicing at the C-terminal end of sepL in the precursor sepL  espADB transcript	Generates the sepL and espADB transcripts	Lodato and Kaper, 2009 [53]
RpoS	EHEC	Binding to ler prom oter	Activates or represses LEE expression, depending on the strain background	Sperandio et al., 1999 [57]; Laaberki et al., 2006 [58]; Tomoyasu et al., 2005 [56]; Iyoda and Watanabe, 2005 [37]
Quorum sensing
KdpE	EHEC	Binding to ler promoter	Activates LEE expression	Njoroge et al., 2013 [70]
QseA	EPEC, EHEC	Binding to ler promoter	Activates LEE transcription	Sperandio et al., 2002 [80]; Sircili et al., 2004 [71]
QseC	EHEC	Phosphorylation of KdpE RR	Activates LEE expression	Sperandio et al., 2002 [80]
QseD	EHEC	Binding to ler promoter	Represses LEE transcription	Habdas et al., 2010 [83]
QseE	EHEC	Inhibiting RcsB RR transcription	Represses LEE expression	Reading et al., 2007 [81]; Njoroge et al., 2013 [70]
RcsB	EHEC O157:H7; EHEC Sakai		Activates LEE transcription	Njoroge et al., 2013 [70]
GlmY/GLMz	EHEC		Regulates transcription of LEE4 and LEE5	Gruber and Sperandio, 2014 [66]