Pathogenic Neisseriae: Gonorrhea, Neonatal Ophthalmia and Meningococcal Meningitis (page 3)
(This chapter has 7 pages)
© 2008 Kenneth Todar, PhD
Virulence Factors
Like the other pyogenic bacteria, Neisseria gonorrhoeae has a
wide
range of virulence determinants, although it does not produce any
exotoxins.
The first stages of infection, involving adherence and invasion, are
mediated
by surface components of the gonococci. The bacterium first attaches to
epithelial cells by means of its fimbriae, specifically N-methylphenylalanine
(Type 4) pili, the main subunit of which is PilE. After
initial
attachment, the bacteria enter a second stage of binding mediated by
the
outer membrane protein
P.II
(also known as Opa) which is
needed for tight binding and invasion of epithelial cells. Also, P.II
from one bacterium will bind to LOS of an adjacent bacterium, which
allows
for the construction of a microcolony which may be functionally
analogous
to a biofilm. However, the invasion of a cell involves a single
bacterium,
not whole microcolonies.
Neisseria gonorrhoeae also produces an
IgA1 protease that probably play a role in the colonization stage.
The outer membrane porin of N. gonorrhoeae P.I (also
known
as Por) is equivalent to the ompC and ompF porins of E.
coli
that are involved in the passage of solutes through the outer
membrane.
However, P.I apparently has a role in virulence that allows the
gonococci
to survive inside of phagocytes. Purified P.I has been shown to inhibit
the ability of phagocytes to kill ingested bacteria.
The lipooligosaccharide (LOS) of the outer membrane is thought to be
responsible for most of the symptoms of gonorrhea. Gonococcal LOS
triggers
an intense inflammatory response. Subsequent activation of complement,
attraction and feeding by phagocytes, and the lysis of the phagocytes
themselves,
contributes to the purulent discharge. The local production of TNF,
elicited
by LOS, is thought to be the main cause of damage to the fallopian
tubes.
In addition, in strains that cause systemic infection, LOS binds sialic
acid from the serum forming a microcapsule of sialylated LOS,
which
allows the gonococci to resist the host immune response and serum
bactericidal
reaction.
Nonsialyated LOS and P.I (Por) on the bacterial surface are known to
be effective targets for bactericidal antibodies. However, if
antibodies
produced against P.III (also known as Rmp) react with
their
antigenic site on the gonococcal surface, the effect is to block
bactericidal
antibodies against LOS and P.I and to protect the bacterium from
complement-mediated
lysis.
Finally, Neisseria gonorrhoeae has a well-developed iron
acquisition
system that permits it to extract iron from its host during growth,
which
is necessary to support bacterial invasion. Basically, the bacterium is
able to form two transferrin receptors (Tbp1 and Tbp2)
and
one lactoferrin receptor (Lbp) in its outer membrane, which are
induced under low-iron conditions, and which are able to directly
extract
iron from transferrin and lactoferrin, respectively. The proteins can
also
extract iron from heme and hemoglobin.
Table 1. Surface
components of N.
gonorrhoeae that may play a role in virulence
| Designation |
Location |
Contribution |
| PilE |
major fimbrial protein |
initial binding to epithelial cells |
| P.II (Opa) |
outer membrane protein |
contributes to invasion |
| P.I (Por) |
outer membrane porin |
may prevent phagolysosome formation in
neutrophils and/or reduce oxidative
burst |
| LOS |
outer membrane lipooligosaccharide |
elicits inflammatory response, triggers
release of TNF |
| P.III (Rmp) |
outer membrane protein |
elicits formation of ineffective antibodies
that block that block bactercidal
antibodies against P.I and LOS |
| Tbp1 and Tbp2 |
outer membrane receptors for transferrin |
iron acquisition for growth |
| Lbp |
outer membrane receptor for lactoferrin |
iron acquisition for growth |
