562
Bacterial Pathogenesis, Molecular Basis of
5.1
Transmission of Pathogens to the Host and
Host Susceptibility
The information regarding the effective
transmission of a pathogen to its host
is somewhat limited. Some pathogens
such as
B. pertussis
,th
ec
au
s
a
t
i
v
eag
en
t
of whooping cough, can be transmitted
via aerosols created by sneezing. Others,
including
Treponema pallidum
and
Neisse-
ria gonorrhoeae
, which cause syphilis and
gonorrhea respectively, are transmitted via
sexual contact. Some organisms rely on
transmission via animal or arthropod vec-
tors.
Borrelia burgdorferi
,thecauseofLyme
disease is transmitted by the deer tick,
which can bite humans and in effect inoc-
ulate them with the organism. Still others,
such as
V. cholerae
, are internalized by in-
gestion of contaminated matter or via the
fecal–oral route.
Within the host, any available surface
is a potential target for bacterial attack.
However, not all pathogens can interact
with all surfaces or, for that matter, infect
a
l
lhos
ts
.Somepa
thogensmaybeab
leto
interact with a wide variety of cells and
tissues, whereas others are restricted to
speciFc cell types. This demonstrates that
some microorganisms exhibit preferences
for speciFc tissues and hosts. ±or example,
N. gonorrhoeae
can only infect humans
and more speciFcally only certain mucosal
surfaces. In contrast,
P. aeruginosa
can
cause a wide variety of infections affecting
various tissues in a number of hosts.
There is increasing evidence that some
factors may predispose a given host to
infection with a given pathogen and
that the severity of the disease may
actually be modulated by these factors.
A prime example is the NRAMP1 protein,
which was initially identiFed in mice but
which has also recently been identiFed in
humans. This protein is located on the
surface of macrophages, cells that are part
of the immune system and that are used
to engulf bacteria and destroy them, where
it functions as a transporter of speciFc
metals such as iron and manganese into
the mammalian cell. Mutation of this
protein leads to increased susceptibility
to
infection with
organisms
such
as
Mycobacterium spp
.As
ing
l
eam
inoa
c
id
mutation (glycine at position 169 changed
to aspartate) is highly associated with this
increased susceptibility. It is proposed that
thelossofproperfunct
ionofth
isprote
in
results in increased levels of such metals
in the extracellular spaces. Since these
metals are essential for the basic growth
requirement of all cells including bacteria,
it is proposed that the increased availability
of the metals allows the pathogens to thrive
in an environment in which these metals
would normally be limited in supply.
±urthermore, since the metals are used
by bacteria as integral components of
enzymes required to defend against host
defenses, the availability of the metals
in NRAMP1 mutant hosts would allow
the organisms to resist those defenses
and survive.
5.2
Entry into the Host
The primary barrier to infection is the
epithelium, which is considered part of
the human hosts’ innate immunity. Bac-
teria may breach this protective layer in
many ways. One approach is to enter
through breaks in the skin caused by
trauma, including cuts, burns, and insect
bites.
Pseudomonas aeruginosa
is an oppor-
tunistic pathogen that can cause horriFc
infections of individuals who suffer burn
trauma. Arthropod vectors can transmit
Yersinia pestis
,thecausa
t
iveagen
to
fthe
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