Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes

• Published in: Nature reviews. Microbiology Vol. 10; no. 2; pp. 87 - 99
• Main Authors: Radolf, Justin D., Caimano, Melissa J., Stevenson, Brian, Hu, Linden T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2012; Nature Publishing Group
• Subjects: 631/326/417/1716; 692/699/255/1318; Animals; Animals, Wild - microbiology; Animals, Wild - parasitology; Arachnids; Arthritis; Arthropoda; Biomedical and Life Sciences; Borrelia burgdorferi; Borrelia burgdorferi - genetics; Borrelia burgdorferi - physiology; Cell Wall - physiology; Deer; Eggs; Erythema; Gene Expression Regulation, Bacterial - physiology; Genetics; Host-Parasite Interactions - physiology; Humans; Immunology; Infections; Infectious Diseases; Ixodes - microbiology; Ixodes - physiology; Ixodidae; Larva - microbiology; Life Sciences; Lyme disease; Lyme Disease - microbiology; Lyme Disease - parasitology; Lyme Disease - transmission; Medical Microbiology; Mice - microbiology; Mice - parasitology; Microbiology; Molecular biology; Nymph - microbiology; Parasitology; Phylogenetics; Physiological aspects; Prototypes; Public health; review-article; Skin; Vector-borne diseases; Vertebrates; Virology; United States; Northern Hemisphere; United States > US; Connecticut
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro2714

Key Points
Lyme disease first came to public attention in the 1970s as a result of an epidemic of oligoarthritis in children and adults living in the vicinity of the town of Lyme, Connecticut, USA. The observation that infected individuals had a skin lesion called erythema migrans was crucial to identifying the causative agent (the spirochaete
Borrelia burgdorferi
) and its arthropod vector (
Ixodes scapularis
).Lyme disease is now known to be worldwide in distribution and is a major public health problem in the United States.
B. burgdorferi
is perpetuated in an enzootic cycle in which uninfected larval ticks acquire the spirochaete by feeding on an infected reservoir host, usually a small mammal (for example, the white-footed mouse,
Peromyscus leucopus
). The infected larvae moult to become nymphs, which then transmit the bacterium to an uninfected animal with the next blood meal. The outcome of infection is variable and dependent on the mammalian host. Humans are an incidental, dead-end host.
B. burgdorferi
has an unusual genome consisting of a 1 Mb linear chromosome and numerous linear and circular plasmids. The plasmids are a primary repository for differentially expressed lipoproteins. The bacterium is an auxotroph for all amino acids, nucleotides and fatty acids; it also lacks genes encoding enzymes for the tricarboxylic acid cycle and oxidative phosphorylation.
B. burgdorferi
resembles a Gram-negative bacterium in that it contains both outer and inner membranes. However, the architecture and composition of its outer membrane differ markedly from those of Gram-negative bacteria. Most notably, decorating the surface of
B. burgdorferi
are differentially expressed outer-surface lipoproteins. As with all spirochaetes, the organelles of motility (the flagella) are located in the periplasmic space.
With the onset of the nymphal blood meal, spirochaetes in flat nymphal ticks undergo extensive changes in gene and protein expression that enable transmission of
B. burgdorferi
to the mammalian host. Many of these transcriptional changes are regulated by the response regulatory protein 2 (Rrp2)–RpoN–RpoS and histidine kinase Hk1–Rrp1 pathways.
Following transmission, borrelial virulence determinants (for example, OspC) act in concert with tick salivary components (SALPs) to enable the bacterium to establish a foothold at the bite site and subsequently disseminate.
The presence of spirochaetes locally and in tissues following dissemination triggers innate immune pathogen-sensing mechanisms (for example, Toll-like receptors), which recruit circulating leukocytes and orchestrate the development of the adaptive response. Macrophages are thought to be crucial innate immune effectors for bacterial clearance.
Clearance of organisms is dependent on the appearance of specific antibodies. Spirochaetes counter the humoral response of the host by downregulating target surface antigens and activating the recombinatorial surface lipoprotein system (
vls
) for antigenic variation.
Justin Radolf and colleagues summarize our accumulated knowledge of the molecular biology and virulence of
Borrelia burgdorferi
, and its interactions with the arthropod vector and mammalian hosts.
In little more than 30 years, Lyme disease, which is caused by the spirochaete
Borrelia burgdorferi
, has risen from relative obscurity to become a global public health problem and a prototype of an emerging infection. During this period, there has been an extraordinary accumulation of knowledge on the phylogenetic diversity, molecular biology, genetics and host interactions of
B. burgdorferi
. In this Review, we integrate this large body of information into a cohesive picture of the molecular and cellular events that transpire as Lyme disease spirochaetes transit between their arthropod and vertebrate hosts during the enzootic cycle.