''Borrelia miyamotoi'' is a

bacterium Bacteria (; : 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 the ...

of the

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

phylum 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 by ticks. Other species of ''Borrelia'' cause relapsing fever, and are ...

''. A

zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...

organism, ''B. miyamotoi'' can infect humans through the bite of several species of hard-shell ''

Ixodes ''Ixodes'' is a genus of hard-bodied ticks (family Ixodidae). It includes important disease vectors of animals and humans ( tick-borne disease), and some species (notably '' Ixodes holocyclus'') inject toxins that can cause paralysis. Som ...

'' ticks, the same kind of ticks that spread ''B. burgdorferi'', the causative bacterium of

Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...

. Ixodes ticks are also the primary

vector Vector most often refers to: * Euclidean vector, a quantity with a magnitude and a direction * Disease vector, an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematics a ...

in the spread of

babesiosis Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukaryotic parasite in the order Piroplasmida, typically a ''Babesia'' or '' Theileria'', in the phylum Apicomplexa. Human babesiosis transmission via ...

and

anaplasmosis Anaplasmosis is a tick-borne disease affecting ruminants, dogs, and horses, and is caused by ''Anaplasma'' bacteria. Anaplasmosis is an infectious but not contagious disease. Anaplasmosis can be transmitted through mechanical and biological vector ...

. ''B. miyamotoi'' causes ''Borrelia miyamotoi'' disease (BMD) in humans. BMD is a

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, soft-bodied ticks (genus '' Ornithodoros''), or hard-bodied ticks (Genus Ixodes). ...

illness that has been reported across the world, often in the same geographic areas where Lyme disease is endemic. Treatment currently follows that of Lyme disease.

Microbiology

History and morphology

''B. miyamotoi'' was discovered in 1995 when it was isolated from a population of '' Ixodes persulcates'' ticks on the

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

ese island of

Hokkaido is the list of islands of Japan by area, second-largest island of Japan and comprises the largest and northernmost prefectures of Japan, prefecture, making up its own list of regions of Japan, region. The Tsugaru Strait separates Hokkaidō fr ...

. The organism was named for Kenji Miyamoto, who initially discovered ''Borrellia'' spirochetes in Japan. It was first detected in the United States in 2001. ''B. miyamotoi'' is a

gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: *Adhesive#Anaerobic, Anaerobic ad ...

, obligate parasitic bacterium with a spiraling corkscrew shape.

Genetics

The bacterial

genome 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 genes, other functional regions of the genome such as ...

is physically made up of one linear

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

, twelve linear

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 and ...

s, and two circular plasmids, which encode a total of 1362

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s. Four distinct

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

s of ''B. miyamotoi'' have been demonstrated based on examples isolated from Asia, Europe, and North America. ''Borrelia'' species that cause human disease are classified into two genetic

clade In biology, a clade (), also known as a Monophyly, monophyletic group or natural group, is a group of organisms that is composed of a common ancestor and all of its descendants. Clades are the fundamental unit of cladistics, a modern approach t ...

s, the Lyme borreliosis (LB) clade, and the relapsing fever (RF) clade. ''B. miyamotoi'' is a member of the relapsing fever (RF) clade. The ''glpQ'' gene and its resulting GlpQ protein are conserved in the RF clade of ''Borrelia'', which makes it possible to distinguish them from LB group ''Borrellia'' in testing.

Transmission

Unlike ''B. burgdoferi'', ''B. miyamotoi'' exhibits transovarial transmission, whereby the bacterium is passed from an adult tick directly into the eggs of new larvae within the ovaries. This mode of transmission has implications for diagnosis of disease because a very small larva can attach to a human host and go undetected.

Virulence factors

''B. myomotoi'' employs

antigenic variation Antigenic variation or antigenic alteration refers to the mechanism by which an Pathogen, infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host (biology), host immune r ...

and variable membrane proteins (VMPs) that help it to evade the human immune system. It is also known to evade components of the complement cascade, part of

innate immune system The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...

, which mounts the initial response to an infection.

Disease

History

''Borellia miyamotoi'' disease (BMD) in humans was first described in Russia in 2011, then subsequently in Japan, China, North America, Western Europe, and Asia.

Reservoirs

Several variations of

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' ...

and

vole Voles are small rodents that are relatives of lemmings and hamsters, but with a stouter body; a longer, hairy tail; a slightly rounder head; smaller eyes and ears; and differently formed molars (high-crowned with angular cusps instead of lo ...

s are known rodent reservoirs for ''B. miyamotoi'', including ''

Apodemus ''Apodemus'' is a genus of Muridae, murid (true mice and rats) containing the field mice as well as other well-known species like the wood mouse and the yellow-necked mouse. The name is unrelated to that of the ''Mus (genus), Mus'' genus, instead ...

'' spp., ''Myodes glareolus'', and ''Peromyscus leucopus''. There is also some preliminary evidence for various avian and several large animal reservoirs such as wild boar and deer.

Vector

The primary vector for ''B. miyamotoi'' transmission is the hard-shell ''

'' tick. Specific species of the tick have been identified in different parts of the world.

Clinical presentation

BMD presents approximately two weeks after infection with non-specific

flu-like symptoms Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...

including a relapsing-remitting fever in excess of 40C (104F), malaise, myalgias (muscle pain), arthralgias (joint pain), nausea, vomiting, and headache. Some patients may have elevated liver transaminases, thrombocytopenia, and leukopenia. Cases involving an

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 ...

rash, which is a classic feature of Lyme disease, have been reported, but are believed to likely be the result of co-infection with ''B. burgdorfer''i and the development of co-morbid Lyme disease. ''B. miyamotoi'' has also demonstrated a slower onset neurological syndrome including meningitis in some immunocompromised patients. Since ticks in all phases of their life cycle, including very small larvae, can transmit the disease to humans, the bite and tick can easily go undetected. ''B. miyamotoi'' also transmits faster than ''B. burgdorfi'', often within 24 hours of tick attachment.

Diagnosis

PCR tests are available for Borrelia Miyamotoi https://www.mayocliniclabs.com/test-catalog/overview/618298

Polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...

(PCR) testing for the 16S

ribosomal DNA The ribosomal DNA (rDNA) consists of a group of ribosomal RNA encoding genes and related regulatory elements, and is widespread in similar configuration in all domains of life. The ribosomal DNA encodes the non-coding ribosomal RNA, integral struc ...

, ''fla,'' or p66 genes have been used in specialized labs. PCR for the glpQ gene can be used to rule out Lyme disease since LB clade Borrelia species don't contain it, however a positive test doesn't necessarily indicate ''B. miyamotoi'' infection because the gene exists in all RF clade ''Borrelia'' species. An investigational method of detection involving combined serologic testing for IgG and

IgM Immunoglobulin M (IgM) is the largest of several isotypes of antibodies (also known as immunoglobulin) that are produced by vertebrates. IgM is the first antibody to appear in the response to initial exposure to an antigen; causing it to also ...

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

against both the GlpQ and VMP proteins has recently shown high sensitivity and specificity.

Treatment

Antibiotics used for Lyme disease are generally recommended for BMD. Though no prospective studies nor formal guidelines have been developed, these antibiotics have been reported to be effective.

Doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...

or ceftriaxone are usually recommended. A possible resistance to amoxicillin was noted in an ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' study, but the significance for humans is unknown. The

Jarisch–Herxheimer reaction A Jarisch–Herxheimer reaction is a sudden and typically transient reaction that may occur within 24 hours of being administered antibiotics for an infection by a spirochete, including syphilis, leptospirosis, Lyme disease, and relapsing fever. Si ...

has been noted at the start of antibiotic treatment for BMD.

References

External links

CDC - Borrelia miyamotoi Disease
https://www.mayocliniclabs.com/test-catalog/overview/618298 {{Taxonbar, from=Q3330965 miyamotoi Bacteria described in 1995