Type 1 and 5 secretion systems and associated toxins - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 503

self-recognition process mediated by receptor-ligand reactions between Ag43
molecules on adjacent cells ( Hasman et al., 1999; Kjaergaard et al., 2000a ). The
autoaggregation property of Ag43 is also characteristic of many other autotrans-
porter proteins including AIDA-I and TibA ( Sherlock et al., 2004, 2005b ).
Finally, Antigen 43 dramatically enhances biofilm formation on abiotic sur-
faces ( Danese et al., 2000; Kjaergaard et al., 2000b; Torres et al., 2002; Reisner
et al., 2003 ) and is specifically correlated with the biofilm mode of growth
( Schembri et al., 2003b ). Ag43 expression is correlated with biofilm formation
by UPEC during infection of bladder cells ( Anderson et al., 2003 ) and in entero-
pathogenic E. coli ( Torres et al., 2002 ). Global gene expression profiling of E.
coli during biofilm growth demonstrated that agn43 expression is up-regulated
when compared with both exponential and stationary phase planktonic cultures
( Schembri et al., 2003b ). Further, a comparison of the biofilm-forming capac-
ity of Ag43 variants from different pathogenic E. coli strains demonstrated a
conserved ability of Ag43 to enhance biofilm growth, albeit with different effi-
ciency ( Klemm et al., 2004 ). Ag43-mediated aggregation also protects bacteria
against hydrogen peroxide, a phenomenon that may enhance the resistance of
biofilm cells to antimicrobial agents ( Schembri et al., 2003a ).
Plasmid encoded toxin (Pet)
SPATEs are a subgroup of AT proteins that possess a consensus serine protease
domain ( Henderson et al., 1998 ). They have been identified in many pathogenic
E. coli and other species such as Shigella, Citrobacter , and Salmonella . SPATE
proteins possess several common features: (1) SPATE members do not cleave
IgA1; (2) the serine protease domain is not involved in autoprocessing; (3)
most SPATE proteins are the predominant secreted molecule of the strain; (4)
SPATE proteins are highly associated with pathogenic strains; and (5) SPATEs
are highly immunogenic. Interestingly, despite having the same serine protease
domain, the SPATE proteins demonstrate distinct substrate specificities. SPATE
proteins are among the best-characterized AT proteins of E. coli and possess
a range of functional properties including cytotoxicity ( Brunder et al., 1997;
Eslava et al., 1998; Mellies et al., 2001; Guyer et al., 2002 ), mucinase activity
( Parham et al., 2004 ), hemoglobin degradation ( Provence and Curtiss, 1994;
Otto et al., 1998 ) and promotion of intestinal colonization ( Leyton et al., 2007 ).
Some SPATE proteins including Pet and EspP are located on plasmids, while
others are encoded on chromosomal pathogenicity islands.
One of the best-characterized SPATEs is the Plasmid-Encoded Toxin (Pet).
Pet is encoded on pAA2, the large virulence plasmid of enteroaggregative
E. coli (EAEC) strain 042. The expression of Pet was recently shown to be
co-dependent on the two global regulators CRP and Fis ( Rossiter et al., 2011a ).
This regulation is via a novel co-activation mechanism whereby CRP is placed
at a non-optimal position for transcription initiation, creating dependence on Fis
for full activation of pet . Other SPATEs were found to have similar promoters
suggesting similar co-dependent regulation.