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Rickettsial Diseases, including Typhus and Rocky Mountain Spotted Fever
(This chapter has 6 pages)
© Kenneth Todar, PhD
Introduction to the Rickettsiae
The Rickettsiae are small (0.3-0.5 x 0.8-2.0 um),
aerobic, coccobacilli that are obligate intracellular parasites of
cells. They may reside in the cytoplasm or within the nucleus of the
that they invade. They divide by binary fission and they metabolize
glutamate via aerobic respiration and the citric acid (TCA) cycle.
They have typical Gram-negative cell walls, and they lack flagella. The
rickettsiae frequently have a close relationship with arthropod vectors
that may transmit the organism to mammalian hosts. The rickettsiae have
very small genomes of about 1.0-1.5 million bases.
Rickettsia prowazekii, the cause of epidemic typhus, is the
prototypical rickettsia. Typhus has plagued humanity throughout
history. The American bacteriologist, Hans
Zinsser, to whom this textbook is dedicated, was able to grow the
elusive intracellular pathogen and develop a protective vaccine for
typhus fever. He wrote a book about the bacterium, published in 1935, Rats,
a study in biography, which, after 12 preliminary chapters
for the preparation of the lay reader, deals with the life history of
Rickettsia prowazekii has made science news recently since it
has been shown to be the probable origin of eucaryotic
mitochondria. Its complete genome sequence of 1,111,523 base pairs has
been shown to contain 834
protein-coding genes. The functional profiles of these genes show
similarities to those of mitochondrial genes. No genes required for
glycolysis are found in either R. prowazekii or mitochondrial
genomes, but a complete set of genes encoding components of the
tricarboxylic acid cycle and the respiratory-chain complex is found in
both. In effect, ATP production in the rickettsia is the same as
that in mitochondria. Many genes involved in the biosynthesis and
regulation of biosynthesis of amino acids and nucleosides in
free-living bacteria are absent from R. prowazekii and
Such genes seem to have been replaced by homologues in the nuclear
(host) genome. Phylogenetic analyses indicate
that R. prowazekii is more closely related to mitochondria than
it is to any bacterium on the Tree of Life.
Rickettsiae must be grown in the laboratory by co-cultivation with
cells, and they have not been grown by in axenic culture. The basis of
their obligate relationship with eucaryotic cells has been explained by
rickettsial possession of "leaky membranes" that require the osmolarity
and nutritional environment supplied by an intracellular habitat.
The rickettsiae, in spite of their small size and obligate
habitat, are a group of alphaproteobacteria, which
many well-known organisms such as Acetobacter, Rhodobacter,
few of the alphaproteobacteria are pathogens of humans. Brucella,
Rickettsia, and a related intracellular parasite, Ehrlichia,
are the main exceptions.
The genus Rickettsia is included in the
bacterial family Rickettsiaceae
of the order Rickettsiales. This
includes many species associated with human disease,
including those in the spotted fever group and the typhus group
(figure 1). The rickettsiae that are pathogens of humans are subdivided
into three major
groups based on clinical characteristics of disease: 1. spotted fever
group; 2. typhus group; and 3.
Figure 1. Taxonomic
of the order Rickettsiales
Spotted Fever Group (SFG)
Rickettsia rickettsii is the cause of Rocky Mountain spotted
fever (RMSF) and is the prototype bacterium in the spotted fever
of rickettsiae. Rickettsia rickettsii is found in the
and is transmitted to humans through the bite of infected ticks. The
infects human vascular endothelial cells, producing an inflammatory
The pathogenesis of RMSF is discussed in some detail below.
Other spotted fever group rickettsiae that produce human
include R. conorii, R. mongolotimonae and R. slovaca
fever and similar illnesses), R.
japonica (Japanese spotted fever), R. sibirica (North Asian
typhus), R. africae (African tick bite fever), R.
(perimyocarditis), and R.
honei (Flinders Island spotted fever). The spotted fever
have been found on every continent except Antarctica.
Two "transitional group" (other) rickettsias cause spotted fever-like diseases: R. akari (rickettsial pox), and R. australis (Queensland tick typhus).
Typhus Group (TG)
Rickettsia prowazekii is the cause of epidemic or louse-borne
typhus and is the prototypical bacterium from the typhus group
rickettsiae. R. prowazekii infects human vascular endothelial
vasculitis. In contrast to RMSF, louse-borne typhus tends to occur in
winter. Infection usually is transmitted from person to person by the
louse and, therefore, tends to manifest under conditions of crowding
poor hygiene. The southern flying squirrel is apparently the reservoir
in the United States, but the vector involved in transmission from the
flying squirrel to humans is unknown. The disease has a worldwide
Other rickettsiae in the typhus group include R. typhi and R.
felis. Murine typhus is caused by transmission of R. typhi
rats, cats and opossums to humans via a flea vector. Murine typhus is
worldwide and is endemic to areas of Texas and southern California in
United States. Although
R. felis is phylogenetically more closely
related to the spotted fever group of rickettsiae than the typhus
it shares antigens with R. typhi and produces a murine
illness. Rickettsia felis has been detected in cat fleas and
Scrub Typhus Group (STG)
Orientia (Rickettsia) tsutsugamushi is the cause of scrub
Originally called Rickettsia tsutsugamushi, this organism was
its own genus designation because it is phylogenetically distinct from
the other rickettsiae, though closely related. Orientia
transmitted to humans by the bite of trombiculid mites (chiggers),
are the vector and host. Scrub typhus occurs throughout much of Asia