Biology of Infection with Borrelia burgdorferi
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Natural history of the Lyme disease spirochete
The causative agent of Lyme disease is a member of the eubacterial phylum Spirochaetes. Members of this group of organisms share a distinctive morphology that includes a spiral or wavelike body and flagella (organs of motility) enclosed between the outer and inner membranes. The spirochetes include several human pathogens, including Treponema pallidum (agent of syphilis), Leptospira interrogans (leptospirosis), and several Borrelia spp that cause relapsing fever. Although these other
Genome and molecular genetics of Borrelia burgdorferi
Although the underlying genetic traits contributing to the differences in disease have not been identified, the release of three Borrelia genome sequences (one from each species) should aid in this endeavor [5], [11], [12], [13]. These genomes have several common features, including a linear chromosome and many smaller DNA molecules (plasmids) that may be linear or circular [14], [15], [16], [17]. The linear structure of the chromosome and many of the plasmids is unusual in the bacterial world,
Borrelia burgdorferi life cycle
B burgdorferi infects a wide range of vertebrate animals including small mammals, lizards, and birds [33], [34], [35], [36], [37], [38], [39]. Ticks of the genus Ixodes transmit B burgdorferi between hosts and are the only natural agents through which humans have been shown to become infected [2], [40]. Worldwide geographic distribution of Lyme disease correlates to the overlapping ranges of a competent reservoir host for B burgdorferi and the tick vector. In the northeastern and midwestern
Mammalian components affecting Borrelia burgdorferi infection
Several different experimental animals have been used for laboratory studies of B burgdorferi infection and disease (reviewed by Philipp and Johnson [54]). Hamsters become infected in multiple tissues but do not show signs of disease [55], although arthritis can be induced in vaccinated or irradiated hamsters [56], [57]. Rabbits develop skin manifestations similar to the rash erythema migrans found in human disease but clear the infection relatively rapidly [58], [59]. Dogs develop arthritis
Borrelia burgdorferi products required for mammalian infection
Efforts to identify B burgdorferi products that play roles in mammalian infection began by serially passaging strains in culture and correlating loss of infectivity with loss of specific plasmids [55], [104], [105], [106], [107], [108]. As genetic techniques have become available for B burgdorferi analysis, other approaches have been applied to identifying genes that contribute to mammalian infectivity, and the roles of some such genes have been rigorously defined by inactivation and
Borrelia burgdorferi infection of ticks
While infected nymphal ticks feed, spirochetes in the midgut respond in several ways to the incoming blood and increased temperature. The population of spirochetes expands [156], [157], [158], and their protein synthesis alters [49], [99], [122], [159], [160]. Spirochetes then migrate from the midgut to the salivary glands, allowing transmission into a new host. The B burgdorferi OspA was shown to be abundant on the surface of bacteria resident in ticks (see Fig. 1) but down-regulated during
Summary
B burgdorferi produces a number of products that allow it to colonize and persist in its natural mammalian and tick hosts. Although the functions of only a few B burgdorferi products have been clearly defined, some (such as OspC) are required for the bacteria to survive the initial attack of the mammalian innate immune system, whereas others (like VlsE) contribute to resisting the subsequent acquired immune response. Bacterial factors such as RpoS and RpoN are components of the signaling
Acknowledgements
The authors thank Catharine Bosio, Claire Checroun, and Mollie Jewett for comments on the manuscript, and Gary Hettrick and Anita Mora for graphical expertise.
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This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.