Type 3 secretion systems - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 408

for putative elements of the injectisome, while the eip locus contains six genes
including a putative translocon, effector and regulator ( Figure 14.1 C), related in
sequence to the inv/mxi/spa systems including the Salmonella typhimurium SPI-1
and Shigella T3SSs. However, sequence comparison reveals that in most strains,
many mutations and sequence deletions are present, leading to the proposition that
this system is non-functional ( Ren et al., 2004 ). Nonetheless, expression of several
ETT2 genes, under the control of the putative regulator, has been reported ( Sheikh
et al., 2006 ).
STRUCTURE AND ORGANIZATION OF THE T3SS INJECTISOME
One of the most striking aspects of T3S is the encoded secretion system, a ∼3.5
MDa macromolecular apparatus often referred to as the 'injectisome'. Since its
first observation in Salmonella typhimurium ( Kubori et al., 1998 ), our under-
standing of the T3SS structure and assembly has expanded through a combina-
tion of structural and genetic studies. It is composed of >20 different proteins,
many of them in a highly oligomerized state. Electron microscopic (EM) analy-
sis from various species shows a syringe-shaped structure ( Figure 14.2 ) with
a central hollow channel approximately 30 Å wide ( Marlovits et al., 2004 ;
Schraidt and Marlovits, 2011 ), constituting the proposed path through which
T3S effectors are translocated.
For historical reasons, the nomenclature used to name the genes of the T3SS
has not been standardized. As a consequence, the names of individual proteins
vary between different T3SSs (see Table 14.1 for T3SS nomenclature from dif-
ferent systems). In order to simplify this chapter, the EPEC LEE T3SS nomen-
clature will be used for general description of individual proteins.
The basal body
The basal body of the injectisome refers to the large substructure spanning from
the bacterial cytosol through to the inner and outer membranes of the bacterium
(see Figure 14.2 ). The precise definition of what constitutes the basal body varies
somewhat in the published literature; here, we will use this term to describe the
structural components spanning both bacterial membranes and the periplasmic
space, excluding the needle projecting outward as well as the inner-membrane
export apparatus. High-resolution EM reconstruction of the basal body from the
Salmonella SPI-1 T3SS ( Marlovits et al., 2004, 2006 ; Schraidt and Marlovits,
2011 ), as well as that from Shigella ( Blocker et al., 2001 ; Hodgkinson et al.,
2009 ) have revealed they are composed of several concentric, symmetrical rings,
resembling the basal body found in the flagellum.
The inner-membrane region of the basal body in the EPEC T3SS is com-
posed of two proteins, EscD and EscJ, forming an intimately associated pair
of 24-mer oligomeric rings ( Yip et al., 2005b ; Schraidt et al., 2010 ; Schraidt
and Marlovits, 2011 ). By analogy with PrgK in the Salmonella SPI-1 system