prowazekii is the pathogenic bacterium responsible for
epidemic typhus fever, an infectious disease that has
plagued humans ever since it was first recorded in Europe
nearly 1000 years ago (Szybalski, 1999). More recently,
R. prowazekii is estimated to have infected nearly 30
million humans following the First and Second World War (Andersson
et al., 1998), and continues to pose a major health threat
in certain parts of the world, despite the availability of
antibiotics. R. prowazekii is typically transmitted
to humans by the body louse – an obligate ectoparasitic
arthropod (Figure 1) (Baxter, 1996). In its vegetative
state, the pleomorphic R. prowazekii is 0.3 μm to 0.5
μm by 0.8 μm to 2.0 μm in size (Walker, 1998), which makes
this species too small to be clearly seen under an ordinary
light microscope. R. prowazekii belongs to a large
group of Gram-negative bacteria known as α-proteobacteria
that multiply in eukaryotic cells. This suggests that they
can only grow and reproduce within the living cells of their
host. Although classified as Gram-negative bacteria, R.
prowazekii are poorly stained by the Gram method and are
better visualized using the Giemsa or Giménez stains (Raoult
et al., 2004).
This image shows an adult female human body louse (Pediculus
humanus humanus) along with two larval young.
Obtained from WHO: World Health Organization (1976).
Intracellular R. prowazekii often
appear as short, paired or single, lanceolate-to-ovoid cocco-bacilli
(Raoult et al., 2004). To undergo cellular respiration, this
species requires oxygen as a terminal electron acceptor. Its envelope consists of three major
layers: an in-innermost cytoplasmic membrane, a thin
electron-dense rigid cell wall containing peptidoglycan, and
an outer layer, which contains lipopolysaccharide endotoxin
(Yu & Walker, 2005) and immunodominant surface-exposed
proteins that provide structure or potentially contribute to
host cell adhesion or other host cell interactions (Figure
2) (Raoult et al., 2004). Cells of R. prowazekii also
possess intracytoplasmic invaginations of the plasma
membrane – a morphological feature that resembles cristae
found in the mitochondria. Unlike the mitochondria, however,
members of this species possess a flagellum for motility – a
feature not common among the family Rickettsiaceae (Yu &
A transmission electron micrograph revealing the
cell envelop of
The red arrow points to the outer layer, the yellow
arrow points to the thin electron-dense rigid cell
wall, and the blue arrow points to the innermost
cytoplasmic membrane [X 196000]. Obtained from Yu &
R. prowazekii requires an intracellular habitat,
cells must be co-cultivated in tissue culture or yolk sac of
developing chicken embryos (Figure 3); hence, a
characteristic colonial morphology is inexistent. Under poor
nutritional conditions, cells of R. prowazekii grow
into long, 4 μm filaments and cease to multiply via
transverse binary fission (Yu & Walker, 2005). However, when
proper conditions are restored, they immediately divide into
their ordinary short rod form and engage in extensive
movements until released by the disruption of massively
infected cells (Tritz, 2000).
This transmission electron micrograph depicts a
chicken embryo fibroblast infected with a large mass
prowazekii. The red arrows point to the
bacteria, the blue arrow points to the fibroblast
cell membrane, and the yellow arrow points to the
nucleus of the fibroblast [X 1200]. Obtained from Yu
& Walker (2005).
The nutritional requirements of
outside their host cell, are not known (Yu & Walker, 2005).
What is known is that R. prowazekii acquires most of its
amino acids from its host cell because only the genes
associated with the biosynthesis of lysine and serine are
present in its DNA (Yu & Walker, 2005). In addition, maximal
growth of this species can only occur if there is a
sufficient amount of host cell proline and serine or glycine
(Yu & Walker, 2005). This implies that
has a highly permeable cytoplasmic membrane. Likewise,
glycolytic intermediates and products, such as acetyl-CoA,
must also be obtained by its host. Similar to the
mitochondrion found in eukaryotic cells, this species
produces its own physiological energy supply of ATP via the
enzyme ATPase (Yu & Walker, 2005). This reason, along with
the evidence suggesting that
shares a phylogenetic relationship with the mitochondria, is
why some biologists speculate that this species may have
given rise to the modern-day mitochondria. Altogether, to be
able to identify this species for diagnostic purposes,
samples containing bacterial cells must be cultivated in
tissue culture at 35°C. Once nutrients are depleted, longer,
more filamentous-like cells with prominent vacuoles will
develop (Figure 4). Infected tissues stained with Giemsa
should show bluish-purple organisms, whereas tissue stained
with Giménez should show bright red organisms, with a
decolorized background stain of pale greenish blue (Yu &
Walker, 2005). Due to the inability to grow
on ordinary microbiological media, such as nutrient broth,
diagnosis is often difficult (Ge
This transmission electron micrograph shows a large
number of free cytoplasmic
late in chicken embryo fibroblast infection. The red
arrow shows an example of a single vacuole-like
structure that appears when nutrients are low or
depleted, and the yellow arrow points to bacteria
dividing by binary fission
Obtained from Yu & Walker (2005).
The entry of R. prowazekii into a
human host cell (typically a phagocyte) involves three
steps: attachment (via OmpA protein and a host cell
receptor), internalization, and escape from the phagosome,
prior to lysosomal fusion (Figure 5) (Yu & Walker, 2005). By
escaping phagosomal digestion, this evasion
the pathogen to reside in the cytoplasm and escape class II
MHC presentation. However, the pathogenic mechanism used
particularly by R. prowazekii as a means to escape
phagosomal entrapment is unclear, but may involve potential
virulence factors, such as phospholipase A (Winkler and
Miller, 1982), antigenic surface proteins, hemolysin, type
IV secretion systems, or hydrolase enzymes (Ge et al.,
This micrograph shows
in the process of escaping phagosomal entrapment.
The red arrow points to a break in the phagosome
membrane [X 31 350]. Obtained from Yu & Walker
Body louse (Pediculus humanus humanus),
the flying squirrel flea (Orchopeas howardii), and
louse (Neohematopinus sciuropteri) are the most
effective vectors in the spread of R. prowazekii-induced
epidemic typhus fever. Once transmitted to the mammalian
host through a bite via arthropod saliva, the bacteria are
found principally in the endothelium of blood vessels,
particularly in those of the brain, skin and heart (Tritz,
2000). This, in turn, causes hyperplasia of endothelial
cells and localized thrombus formation, resulting in
petechial rash, fever – which may reach 39°C – and terminal
shock (Tritz, 2000). Finally, areas of poor hygiene, such as
refugee camps during a major famine or natural disaster, are
places where diseases such as typhus fever tend to flourish.
In fact, due to recent outbreaks in parts of Europe, Africa,
and South America, some experts support the notion that
epidemic typhus is a reemerging public health problem (Ge et al., 2004).
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