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The Rickettsiae are small (0.3-0.5 x 0.8-2.0 um), Gram-negative, aerobic, coccobacilli that are obligate intracellular parasites of eucaryotic cells. They may reside in the cytoplasm or within the nucleus of the cell that they invade. They divide by binary fission and they metabolize host-derived 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, Lice, and History: "being a study in biography, which, after 12 preliminary chapters indispensable for the preparation of the lay reader, deals with the life history of typhus fever".

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 mitochondria. Such genes seem to have been replaced by homologues in the nuclear (host) genome.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 eucaryotic 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 intracellular habitat, are a group of alphaproteobacteria,  which include many well-known organisms such as Acetobacter, Rhodobacter, Rhizobium and Agrobacterium. Very few of the alphaproteobacteria are pathogens of humans. Brucella, Bartonella, 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 genus 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. scrub typhus group.

Figure 1.  Taxonomic classification 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 group of rickettsiae.  Rickettsia rickettsii is found in the Americas and is transmitted to humans through the bite of infected ticks. The bacterium infects human vascular endothelial cells, producing an inflammatory response. The pathogenesis of RMSF is discussed in some detail below.

Other spotted fever group rickettsiae that produce human rickettsioses include R. conorii, R. mongolotimonae and R. slovaca (boutonneuse fever and similar illnesses), R. japonica (Japanese spotted fever), R. sibirica (North Asian tick typhus), R. africae (African tick bite fever),  R. helvetica (perimyocarditis), and R. honei (Flinders Island spotted fever). The spotted fever rickettsiae 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 of rickettsiae. R. prowazekii infects human vascular endothelial cells, producing widespread vasculitis. In contrast to RMSF, louse-borne typhus tends to occur in the winter. Infection usually is transmitted from person to person by the body louse and, therefore, tends to manifest under conditions of crowding and 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 distribution.

Other rickettsiae in the typhus group include R. typhi and R. felis. Murine typhus is caused by transmission of R. typhi from rats, cats and opossums to humans via a flea vector. Murine typhus is found worldwide and is endemic to areas of Texas and southern California in the United States. Although R. felis is phylogenetically more closely related to the spotted fever group of rickettsiae than the typhus group, it shares antigens with R. typhi and produces a murine typhus-like illness. Rickettsia felis has been detected in cat fleas and opossums.