Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...

, or borreliosis, is caused by spirochetal

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

from the

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...

Borrelia ''Borrelia'' is a genus of bacteria of the spirochete phylum. Several species cause Lyme disease, also called Lyme borreliosis, a zoonotic, vector-borne disease transmitted by ticks. Other species of ''Borrelia'' cause relapsing fever, and are tr ...

'', which has 52 known species. Three main species (''

Borrelia garinii ''Borrelia garinii'' is a spirochete bacterium in the genus ''Borrelia ''Borrelia'' is a genus of bacteria of the spirochete phylum. Several species cause Lyme disease, also called Lyme borreliosis, a zoonotic, vector-borne disease transmitted ...

'', ''

Borrelia afzelii ''Borrelia afzelii'' is a species of ''Borrelia'' a bacterium that can infect various species of vertebrates and invertebrates. Among 30 ''Borrelia'' known species, it is one of four which are likely to infect humans causing a variant of Lyme di ...

'', and ''

Borrelia burgdorferi ''Borrelia burgdorferi'' is a bacterial species of the spirochete class in the genus ''Borrelia'', and is one of the causative agents of Lyme disease in humans. Along with a few similar genospecies, some of which also cause Lyme disease, it make ...

s.s.'') are the main causative agents of the disease in humans, while a number of others have been implicated as possibly pathogenic. ''Borrelia''

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

in the

species complex In biology, a species complex is a group of closely related organisms that are so similar in appearance and other features that the boundaries between them are often unclear. The taxa in the complex may be able to hybridize readily with each oth ...

known to cause Lyme disease are collectively called ''

'' ''

sensu lato ''Sensu'' is a Latin word meaning "in the sense of". It is used in a number of fields including biology, geology, linguistics, semiotics, and law. Commonly it refers to how strictly or loosely an expression is used in describing any particular co ...

'' (''s.l.'') not to be confused with the single species in that complex '' Borrelia burgdorferi sensu stricto'' which is responsible for nearly all cases of Lyme disease in North America. ''Borrelia'' are

microaerophilic A microaerophile is a microorganism that requires environments containing lower levels of dioxygen than that are present in the atmosphere (i.e. < 21% O₂; typically 2–10% O₂) for optimal growth. A more re ...

and slow-growing—the primary reason for the long delays when diagnosing Lyme disease have been found to have greater strain diversity than previously estimated. The strains differ in clinical symptoms and/or presentation as well as geographic distribution. Except for ''

Borrelia recurrentis ''Borrelia recurrentis'' is a species of ''Borrelia'', a spirochaete bacterium associated with relapsing fever. ''B. recurrentis'' is usually transmitted from person to person by the human body louse The body louse (''Pediculus humanus humanu ...

'' (which causes louse-borne

relapsing fever Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus ''Borrelia'', which is transmitted through the bites of lice or soft-bodied ticks (genus ''Ornithodoros''). Signs and symptoms Most people who are ...

and is transmitted by the human body louse), all known species are believed to be transmitted by

tick Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...

Species and strains

Until recently, only three genospecies were thought to cause Lyme disease (borreliosis): ''B. burgdorferi'' '' s.s.'' (the predominant species in

North America North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and the Car ...

, but also present in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

); ''B. afzelii''; and ''B. garinii'' (both predominant in

Eurasia Eurasia (, ) is the largest continental area on Earth, comprising all of Europe and Asia. Primarily in the Northern and Eastern Hemispheres, it spans from the British Isles and the Iberian Peninsula in the west to the Japanese archipelago a ...

). Thirteen distinct genomic classifications of Lyme disease bacteria have been identified worldwide. These include but are not limited to ''B. burgdorferi ''s.s.'', B. afzelii, B. garinii, B. valaisana, B. lusitaniae, B. andersoni, 25015, DN127, CA55, 25015, HK501, B. miyamotoi'', and '' B. japonica.'' Many of these genomic groups are country or continent specific. For example, without migration, ''B. japonica'' is only prevalent in the eastern hemisphere. The genomic variations have direct implications on the clinical symptoms of tick-borne Lyme disease. For example, ''B. burgdorferi'' ''s.s.''’s tick-borne Lyme disease may manifest with

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

-like symptoms. In contrast, ''B. garinii''’s tick-borne Lyme disease may cause an infection of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

Emerging genospecies

* ''B. valaisiana'' was identified as a genomic species from Strain VS116, and named ''B. valaisiana'' in 1997. It was later detected by

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...

(PCR) in human

cerebral spinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

(CSF) in

Greece Greece,, or , romanized: ', officially the Hellenic Republic, is a country in Southeast Europe. It is situated on the southern tip of the Balkans, and is located at the crossroads of Europe, Asia, and Africa. Greece shares land borders with ...

. ''B. valaisiana'' has been isolated throughout Europe, as well as east Asia. Newly discovered genospecies have also been found to cause disease in humans: * ''B. lusitaniae'' in Europe (especially Portugal), North Africa and Asia. * ''B. bissettii'' in the United States and Europe. * ''B. spielmanii'' in

. Additional ''B. burgdorferi'' sensu lato genospecies suspected of causing illness, but not confirmed by culture, include ''B. japonica'', ''B. tanukii'' and ''B. turdae'' (Japan); ''B. sinica'' (China); and ''B. andersonii'' (U.S.). Some of these species are carried by ticks not currently recognized as carriers of Lyme disease. The ''B. miyamotoi'' spirochete, related to the

group of spirochetes, is also suspected of causing illness in Japan. Spirochetes similar to ''B. miyamotoi'' have recently been found in both ''

Ixodes ricinus ''Ixodes ricinus'', the castor bean tick, is a chiefly European species of hard-bodied tick. It may reach a length of when engorged with a blood meal, and can transmit both bacterial and viral pathogens such as the causative agents of Lyme disea ...

'' ticks in Sweden and ''I. scapularis'' ticks in the U.S.

Taxonomy

As of 2021, the ''B. burgdorferi'' s.l. species complex is known to include the following

: * '' B. afzelii'' * '' B. americana'' * '' B. andersonii'' (proposed) * '' B. bavariensis'' * '' B. bissettiae'' * '' B. burgdorferi'' s.s. * '' B. californiensis'' * '' B. carolinensis'' * '' B. chilensis'' (proposed) * '' B. finlandensis'' (proposed) * '' B. garinii'' * '' B. japonica'' * '' B. kurtenbachii'' * '' B. lanei'' * '' B. lusitaniae'' * '' B. maritima'' * '' B. mayonii'' * '' B. sinica'' * '' B. spielmanii'' * '' B. tanukii'' * '' B. turdi'' * '' B. valaisiana'' * '' B. yangtzensis'' As these species are mainly differentiated by genetics, they are usually referred to as '' genospecies''.

Epidemiology

Lyme disease is most endemic in

Northern Hemisphere The Northern Hemisphere is the half of Earth that is north of the Equator. For other planets in the Solar System, north is defined as being in the same celestial hemisphere relative to the invariable plane of the solar system as Earth's Nort ...

temperate regions, but sporadic cases have been described in other areas of the world. The number of reported cases of the borreliosis have been increasing, as are endemic regions in North America. Of cases reported to the United States

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

(CDC), the rate of Lyme disease infection is 7.9 cases for every 100,000 persons. In the 10 states where Lyme disease is most common, the average was 31.6 cases per 100,000 persons for 2005. Although Lyme disease has now been reported in 49 of 50 states in the U.S (all but Hawaii), about 99% of all reported cases are confined to just five geographic areas (

New England New England is a region comprising six states in the Northeastern United States: Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont. It is bordered by the state of New York to the west and by the Canadian provinces ...

, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central). In Europe, cases of ''B. burgdorferi'' ''s.l.''-infected ticks are found predominantly in Norway, the Netherlands, Germany, France, Italy, Slovenia, and Poland, but have been isolated in almost every country on the continent. Lyme disease statistics for Europe can be found a
Eurosurveillance website
''Borrelia burgdorferi'' ''s.l.''-infested ticks are being found more frequently in Japan, as well as in northwest China and far eastern Russia. ''Borrelia'' has been isolated in Mongolia as well. In

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...

, tick-borne disease recognition and occurrence is rising. Ticks carrying ''B. burgdorferi'' ''s.l.'', as well as canine and human tick-borne diseases, have been reported widely in Brazil, but the subspecies of ''Borrelia'' has not yet been defined. The first reported case of Lyme disease in Brazil was made in 1993 in

Sao Paulo SAO or Sao may refer to: Places * Sao civilisation, in Middle Africa from 6th century BC to 16th century AD * Sao, a town in Boussé Department, Burkina Faso * Saco Transportation Center (station code SAO), a train station in Saco, Maine, U.S ...

. ''B. burgdorferi'' ''sensu stricto'' antigens in patients have been identified in

Colombia Colombia (, ; ), officially the Republic of Colombia, is a country in South America with insular regions in North America—near Nicaragua's Caribbean coast—as well as in the Pacific Ocean. The Colombian mainland is bordered by the Car ...

and in

Bolivia , image_flag = Bandera de Bolivia (Estado).svg , flag_alt = Horizontal tricolor (red, yellow, and green from top to bottom) with the coat of arms of Bolivia in the center , flag_alt2 = 7 × 7 square p ...

. ''B. burgorferi'' has been reported in Bay Islands of Honduras. In Northern

Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...

, ''B. burgdorferi'' ''s.s.'' has been identified in

Morocco Morocco (),, ) officially the Kingdom of Morocco, is the westernmost country in the Maghreb region of North Africa. It overlooks the Mediterranean Sea to the north and the Atlantic Ocean to the west, and has land borders with Algeria to ...

Algeria ) , image_map = Algeria (centered orthographic projection).svg , map_caption = , image_map2 = , capital = Algiers , coordinates = , largest_city = capital , relig ...

Egypt Egypt ( ar, مصر , ), officially the Arab Republic of Egypt, is a transcontinental country spanning the northeast corner of Africa and southwest corner of Asia via a land bridge formed by the Sinai Peninsula. It is bordered by the Mediter ...

, and

Tunisia ) , image_map = Tunisia location (orthographic projection).svg , map_caption = Location of Tunisia in northern Africa , image_map2 = , capital = Tunis , largest_city = capital , ...

. In

western Western may refer to: Places *Western, Nebraska, a village in the US *Western, New York, a town in the US *Western Creek, Tasmania, a locality in Australia *Western Junction, Tasmania, a locality in Australia *Western world, countries that id ...

and

sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...

, tick-borne

has been recognized for over a century, since it was first isolated by the British physicians

Joseph Everett Dutton Joseph Everett Dutton (9 September 1874 – 27 February 1905) was a British parasitologist who discovered one of the trypanosomes that cause sleeping sickness. He died in the Congo Free State at the age of 30 from tick fever, or African relapsing ...

and

John Lancelot Todd John Lancelot Todd (10 September 1876 – 27 August 1949) was a Canadian physician and parasitologist. Early years John Lancelot Todd was born on 10 September 1876 in Victoria, British Columbia. He was of Anglo-Irish origins. His father was Jacob ...

in 1905. ''Borrelia'' in the manifestation of Lyme disease in this region is presently unknown, but evidence indicates the disease may occur in humans in sub-Saharan Africa. The abundance of hosts and tick vectors would favor the establishment of the infection in Africa. In East Africa two cases of Lyme disease have been reported in

Kenya ) , national_anthem = "Ee Mungu Nguvu Yetu"() , image_map = , map_caption = , image_map2 = , capital = Nairobi , coordinates = , largest_city = Nairobi , ...

. In

Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...

, no definitive evidence exists for the existence of ''B. burgdorferi'' or for any other tick-borne spirochete that may be responsible for a local syndrome being reported as Lyme disease. Cases of

neuroborreliosis Neuroborreliosis is a disorder of the central nervous system. A neurological manifestation of Lyme disease, neuroborreliosis is caused by a systemic infection of spirochetes of the genus ''Borrelia.'' Symptoms of the disease include erythema migr ...

have been documented in Australia, but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.

Lifecycle

The lifecycle of ''B. burgdorferi'' is complex, requiring

s, and species that are competent reservoirs, often small

rodents Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are nat ...

Mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

are the primary

reservoir A reservoir (; from French ''réservoir'' ) is an enlarged lake behind a dam. Such a dam may be either artificial, built to store fresh water or it may be a natural formation. Reservoirs can be created in a number of ways, including contro ...

for the bacteria. Hard ticks have a variety of life histories with respect to optimizing their chance of contact with an appropriate host to ensure survival. The life stages of soft ticks are not readily distinguishable. The first stage to hatch from the egg, a six-legged larva, takes a blood meal from a host, and molts to the first nymphal stage. Unlike hard ticks, many soft ticks go through multiple

nymph A nymph ( grc, νύμφη, nýmphē, el, script=Latn, nímfi, label=Modern Greek; , ) in ancient Greek folklore is a minor female nature deity. Different from Greek goddesses, nymphs are generally regarded as personifications of nature, are ty ...

al stages, gradually increasing in size until the final molt to the adult stage. The lifecycle of the black-legged tick, commonly called the deer tick (''Ixodes scapularis'') comprises three growth stages: the

larva A larva (; plural larvae ) is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle. The ...

and adult. Whereas ''B. burgdorferi'' is most associated with deer ticks and the

white-footed mouse The white-footed mouse (''Peromyscus leucopus'') is a rodent native to North America from Ontario, Quebec, Labrador, and the Maritime Provinces (excluding the island of Newfoundland) to the southwestern United States and Mexico. In the Maritimes, ...

, ''B. afzelli'' is most frequently detected in rodent-feeding vector ticks, and ''B. garinii'' and ''B. valaisiana'' appear to be associated with birds. Both rodents and birds are competent reservoir hosts for ''B. burgdorferi'' ''sensu stricto''. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative immune

complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...

of various host species may determine its reservoir host association.

Genomic characteristics

The genome of ''B. burgdorferi'' (B31 strain) was the third microbial genome ever to be sequenced, following the sequencing of both ''H. influenzae'' and ''M. genitalium'' in 1995, and its chromosome contains 910,725 base pairs and 853 genes. One of the most striking features of ''B. burgdorferi'' as compared with other

is its unusual

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

, which is far more complex than that of its spirochetal cousin ''

Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...

'', the agent of

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...

. In addition to a linear chromosome, the genome of ''B. burgdorferi'' strain B31 includes 21

plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...

s (12 linear and 9 circular) – by far the largest number of plasmids found in any known bacterium. Genetic exchange, including plasmid transfers, contributes to the

pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

of the organism. Long-term culture of ''B. burgdorferi'' results in a loss of some plasmids and changes in expressed protein profiles. Associated with the loss of plasmids is a loss in the ability of the organism to infect laboratory animals, suggesting the plasmids encode key genes involved in

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...

. Chemical analysis of the external membrane of ''B. burgdorferi'' revealed the presence of 46% proteins, 51% lipids and 3% carbohydrates.

Structure and growth

''B. burgdorferi'' is a highly specialized, motile, two-membrane, flat-waved

spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...

, ranging from about 9 to 32 μm in length. Because of its double-membrane envelope, it is often mistakenly described as

Gram negative The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...

, though it stains weakly in

Gram stain In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish ...

. The bacterial membranes in at least the B31, NL303 and N40 strains of ''B. burgdorferi'' do not contain

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

, which is extremely atypical for Gram negative bacteria; instead, the membranes contain

glycolipids Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connec ...

. However, the membranes in the B31 strain have been found to contain a lipopolysaccharide-like component. ''B. burgdorferi'' is a

organism, requiring little oxygen to survive. Unlike most bacteria, ''B. burgdorferi'' does not use iron, hence avoiding the difficulty of acquiring iron during infection. It lives primarily as an

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

pathogen. Like other spirochetes, such as ''

'' (the agent of

), ''B. burgdorferi'' has an axial filament composed of

flagella A flagellum (; ) is a hairlike appendage that protrudes from certain plant and animal sperm cells, and from a wide range of microorganisms to provide motility. Many protists with flagella are termed as flagellates. A microorganism may have f ...

that run lengthways between its cell wall and outer membrane. This structure allows the spirochete to move efficiently in corkscrew fashion through

viscous The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the inter ...

media, such as

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

. ''B. burgdorferi'' is very slow growing, with a doubling time of 12–18 hours (in contrast to pathogens such as ''

Streptococcus ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs ...

'' and ''

Staphylococcus ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical (cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultative ...

'', which have a doubling time of 20–30 minutes).

Morphological variants

''B. burgdorferi'' bacteria occasionally take on roughly spherical or other atypical shapes. These have sometimes been referred to as "cysts" or as " L-forms", but they appear not to be true

microbial cyst A microbial cyst is a resting or dormant stage of a microorganism, usually a bacterium or a protist or rarely an invertebrate animal, that helps the organism to survive in unfavorable environmental conditions. It can be thought of as a state of ...

s and the cautious term "round bodies" is now preferred. As well as ''in vitro'' they have occasionally been observed in tissue samples taken from

erythema migrans Erythema migrans or erythema chronicum migrans is an expanding rash often seen in the early stage of Lyme disease, and can also (but less commonly) be caused by southern tick-associated rash illness (STARI). Page last reviewed: October 22, 2015 ...

rashes. In some ''in vitro'' experiments round bodies seemed to be formed in response to adverse conditions, such as a culture medium containing no serum or antimicrobial drugs. Advocates of the "

chronic Lyme disease Chronic Lyme disease (CLD) is the name used by some people with "a broad array of illnesses or symptom complexes for which there is no reproducible or convincing scientific evidence of any relationship to ''Borrelia burgdorferi'' infection" to ...

" theory sometimes propose the formation of round bodies as a way that ''B. burgdorferi'' could survive standard antibiotic treatment protocols. However, a 2014 review found that there was currently no clear evidence for this, and noted that samples from patients diagnosed as having chronic Lyme disease following antibiotic treatment usually showed no round bodies (and indeed often no spirochaetes), suggesting that their symptoms might be due to something other than surviving ''B. burgdorferi'' bacteria.

Outer surface proteins

The outer membrane of ''B. burgdorferi'' is composed of various unique outer surface proteins (Osp) named OspA through OspF. Osp proteins are

lipoproteins A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

anchored by N-terminally attached fatty acid molecules to the membrane. They are presumed to play a role in virulence, transmission, or survival in the tick. OspA, OspB, and OspD are expressed by ''B. burgdorferi'' residing in the gut of unfed ticks, suggesting they promote the persistence of the spirochete in ticks between blood meals. During transmission to the mammalian host, when the nymphal tick begins to feed and the spirochetes in the midgut begin to multiply rapidly, most spirochetes cease expressing OspA on their surfaces. Simultaneous with the disappearance of OspA, the spirochete population in the midgut begins to express an OspC and migrates to the salivary gland. Upregulation of OspC begins during the first day of feeding and peaks 48 hours after attachment. The OspA and OspB genes encode the major outer membrane proteins of ''B. burgdorferi''. The two Osp proteins show a high degree of sequence similarity, indicating a recent duplication event. Virtually all spirochetes in the midgut of an unfed nymph tick express OspA. OspA promotes the attachment of ''B. burgdorferi'' to the tick protein TROSPA, present on tick gut epithelial cells. OspB also has an essential role in the adherence of ''B. burgdorferi'' to the tick gut. Although OspD has been shown to bind to tick gut extracts ''in vitro'', as well as OspA and OspB, it is not essential for the attachment and colonization of the tick gut, and it is not required for human infections. OspC is a strong

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

; detection of its presence by the host organism stimulates an immune response. While each individual bacterial cell contains just one copy of the ''ospC'' gene, the gene sequence of ''ospC'' among different strains within each of the three major Lyme disease species is highly variable. OspC plays an essential role during the early stage of mammalian infection. In infected ticks feeding on a mammalian host, OspC may also be necessary to allow ''B. burgdorferi'' to invade and attach to the salivary gland after leaving the gut, although not all studies agree on such a role for the protein. OspC attaches to the tick salivary protein Salp15, which protects the spirochete from

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...

and impairs the function of

dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...

. OspE and OspF were initially identified in ''B. burgdorferi'' strain N40. The ''ospE'' and ''ospF'' genes are structurally arranged in tandem as one transcriptional unit under the control of a common promoter. Individual strains of ''B. burgdorferi'' carry multiple related copies of the ''ospEF'' locus, which are now collectively referred to as ''Erp'' (OspE/F-like related protein) genes. In ''B. burgdoreri'' strains B31 and 297, most of the ''Erp'' loci occupy the same position on the multiple copies of the cp32 plasmid present in these strains. Each locus consists of one or two ''Erp'' genes. When two genes are present, they are transcribed as one

operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

, although in some cases, an internal promoter in the first gene may also transcribe the second gene. The presence of multiple Erp proteins was proposed to be important in allowing ''B. burgdorferi'' to evade killing by the

alternative complement pathway The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections. The alternative pathway is one of three complement pathways that opsonize and k ...

of a broad range of potential animal hosts, as individual Erp proteins exhibited different binding patterns to the complement regulator

factor H Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma (at typical concentrations of 200–300 micrograms ...

from different animals. However, the presence of

was recently demonstrated to not be necessary to enable ''B. burgdorferi'' to infect mice, suggesting the Erp proteins have an additional function.

Mechanisms of persistence

''B. burgdorferi'' is susceptible to a number of

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...

in humans. However, untreated ''B. burgdorferi'' may persist in humans for months or years. In North America and Europe, Lyme arthritis may persist, while Europe also includes a persistent skin condition called

acrodermatitis chronica atrophicans Acrodermatitis chronica atrophicans (ACA) is a skin rash indicative of the third or late stage of European Lyme borreliosis. ACA is a dermatological condition that takes a chronically progressive course and finally leads to a widespread atrop ...

. *

Antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

ic variation and

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

Like the ''Borrelia'' that causes

, ''B. burgdorferi'' has the ability to vary its surface proteins in response to

immune In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...

attack. This ability is related to the genomic complexity of ''B. burgdorferi'', and is another way ''B. burgdorferi'' evades the immune system to establish a chronic infection.

References

External links

Atlas of ''Borrelia'' (images of spirochetal, spheroplast and granular forms)

NCBI Taxonomy Browser – ''Borrelia''

''Borrelia burgdorferi'' B31 Genome Page

''Borrelia garinii'' PBi Genome Page

''Borrelia afzelli'' PKo Genome Page
* {{DEFAULTSORT:Lyme Disease Microbiology Bacteriology