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and retract (
Collins et al., 2005
;
Bayan et al., 2006
;
Korotkov et al., 2011
).
As with any secretin, conformational changes are required to permit transport,
and significant changes would be required to accommodate the dynamic T4P
fibers (
Reichow et al., 2010, 2011
). It has been suggested that the BFP machin-
ery drives these conformational shifts, allowing passage of the assembled pilus
(
Hwang et al., 2003
), though exactly how this occurs remains unknown.
Pilus retraction
While the process of pseudopilus retraction is unknown in the T2S, the phe-
notype is well characterized in BFP. Retraction is mediated by BfpF, a sec-
ond hexameric ATPase which localizes to the cytoplasmic face of the IM. BfpF
has homologs in some, but not all T4P systems and none in the T2S system
(
Anantha et al., 1998
). Mutants deficient for
bfpF
do not disaggregate in culture
(
Bieber et al., 1998
;
Knutton et al., 1999
) and may be hyperpiliated, though this
observation has not been quantitatively examined. However, these phenotypic
characteristics are consistent with a lack of pilus retraction in a
bfpF
mutant.
Retraction of BFP facilitates host cell tight junction disruption and efficient
delivery of bacterial host effectors during the course of EPEC pathogenesis
(
Zahavi et al., 2011
). T4P fiber retraction is induced at least partly by BFP bind-
ing to
N-
acetyl lactosamine (
Humphries et al., 2010
).
T4P biogenesis machines can sustain forces of 100 pN during this rapid
process of pilus retraction, during which T4P fibers undergo changes in quater-
nary structure (
Biais et al., 2010
). Such rapid changes in cell surface molecules
likely exert considerable strain on the cell envelope. Similarly, simultaneously
building many molecular machines that span both the IM and OM, such as those
that elaborate T4P or the T2S, also may induce significant cell envelope stress.
Indeed, the accumulation of very high levels of T4P subunits in the periplasm
is cytotoxic in
Neisseria gonorrhoeae
(
Wolfgang et al., 2000
), although not in
N. meningitidis
(
Carbonnelle et al., 2006
).
It is thought that the extension and retraction ATPases in T4P act antago-
nistically during pilus biogenesis (
Maier et al., 2004
). It is not known how the
activities of each ATPase are regulated to favor extension or retraction of the
pilus in any system, however it has been demonstrated in
Myxococcus xanthus
that dynamic switching of the two ATPases across the cell causes extension or
retraction, depending upon which ATPase is predominant at the polar regions
(
Bulyha et al., 2009
). Further, since expression of the retraction ATPase is not
required for pilus polymerization, a double mutant for the retraction ATPase
and an accessory protein not absolutely necessary for pilus biogenesis will still
express T4P on the surface even if pilus assembly is inefficient (
Carbonnelle
et al., 2006
). This strategy can be utilized to determine which proteins are abso-
lutely necessary for the polymerization process, for example T4P are expressed
by
N. meningitidis
(
Winther-Larsen et al., 2005
) and
P. aeruginosa
(
Giltner
et al., 2010
) in the absence of pilin-like proteins and the retraction ATPase,
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