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Host Defenses to Spirochetes

Nicolás Navasa, Erol Fikrig, Juan Anguita

Spirochetes constitute a unique group of bacteria that inhabit are the major immunogens of B. burgdorferi and most likely T.
many different environments, such as soil, arthropods, and pallidum, and thus they are their dominant proinflammatory
mammals. These microorganisms cause numerous human ill- agonists. Five percent of the chromosomal ORFs and 14.5–17%
nesses, including syphilis and Lyme disease. Spirochetes share of the functionally complete ORFs contained in the plasmids of
a typical spiral shape and a distinctive flat-wave morphology. B. burgdorferi encode putative lipoproteins. Interestingly, only
Cellular dimensions vary over a wide range, with a diameter 2.1% of the T. pallidum ORFs encode putative lipoproteins. The
between 0.09 to 0.75 µm and lengths that range from 3 to 500 µm. abundant lipoprotein coding potential of B. burgdorferi suggests
They are motile organisms with a multilayered outer membrane that these molecules may be important for the survival of the
that encapsulates a peptidoglycan layer surrounding their inner spirochete. In fact, as a result of environmental changes, expres-
membrane. Motility is enabled by the presence of endoflagella sion of several B. burgdorferi lipoproteins changes throughout
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located in the periplasmic space. These axial filaments are arranged the lifecycle of the spirochete. For instance, the lipoprotein
in a bipolar fashion and extend toward the opposite end of the outer surface protein (Osp) A is expressed at high levels in the
cell (Fig. 28.1). The viability of the organism is dependent on gut of the unfed tick, but upon feeding OspA expression is
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an intact outer membrane, which can be damaged by variations downregulated, and the expression of OspC increases 90-fold.
in osmolarity, antibodies, or complement resulting in the loss of It is thought that many Osps have adhesive functions, and it
intracellular components and ultimately death of the bacterium. has been shown that OspA is involved in the attachment of B.
Several spirochetal species are able to induce disease in burgdorferi to the gut of the tick through an interaction with the
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mammals (Table 28.1). Lyme disease was first discovered in 1976 tick receptor TROSPA. Furthermore, OspC may be necessary
as an illness affecting a cluster of children in Lyme, Connecticut. for the migration of B. burgdorferi from the gut of the tick to
Several manifestations of the disease, however, had been known the salivary glands and for its survival in the mammalian host.
for over a century in parts of Europe. In 1982, the agent of Lyme Changes in lipoprotein expression are primarily regulated by the
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disease was identified as Borrelia burgdorferi. In contrast, alternative sigma factors, RpoS and RpoN and other unknown
Treponema pallidum subspecies pallidum is the causative agent mechanisms.
of venereal syphilis, a disease that has been recognized for over
5 centuries, although its agent was not identified until 1905. 2 CLINICAL MANIFESTATIONS
The genomes of B. burgdorferi and T. pallidum have been
3,4
sequenced. Despite similar ancestry and morphological features, Lyme Disease
these spirochetes have striking differences at the genetic level, B. burgdorferi sensu stricto (B. burgdorferi) is the etiological agent
which may account for the differences in their lifecycles, envi- of Lyme disease in the United States and other parts of the world,
ronmental adaptations, and the diseases they cause. Both B. whereas B. afzelii and B. garinii are agents of Lyme disease that
burgdorferi and T. pallidum have relatively small genomes are restricted to Europe and Asia. Infection with Lyme disease–
compared with other microorganisms. B. burgdorferi has one of causing spirochetes has also been observed in Japan, Russia, and
the most complex genomes known among prokaryotes, with a China. In the United States, transmission of the spirochete is
single linear chromosome and 21 plasmids, the largest number through the hard-bodied ticks of the Ixodes complex, mainly I.
of plasmids of any characterized prokaryote. Of the 21 plasmids, scapularis and I. pacificus, whereas I. ricinus is responsible for
nine are circular and 12 are linear. Furthermore, less than 10% the transmission of the spirochete in much of Eurasia. According
of B. burgdorferi plasmid-coding regions are found in other to the Centers for Disease Control and Prevention (CDC), Lyme
microorganisms, including spirochetes, which underscore the disease is the most common tickborne disease in the United
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uniqueness of this spirochete among microorganisms. Unlike States and the fifth most common nationally notifiable disease.
B. burgdorferi, T. pallidum contains a single circular chromosome The disease is concentrated in the North Eastern seaboard, with
with no plasmids. Yet, 476 open reading frames (ORFs) in T. further presence in the northern Midwest and the West of the
pallidum have orthologous genes in B. burgdorferi, and almost Continental United States. In Europe, diagnosed Lyme disease
60 of these orthologous genes encode proteins of unknown accounts for more than 65 000 cases annually, which tend to
biological function that are specific to spirochetes. concentrate in countries of Central and Eastern Europe. However,
In contrast to other spirochetes, B. burgdorferi and T. pal- the disease is present to different degrees throughout much of
lidum do not contain lipopolysaccharide (LPS). Lipoproteins Europe. In both the United States and Europe, it is widely believed

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