Borrelia miyamotoi is a Gram-negative bacteria included in the genus Borrelia from the family Spirochaetaceae, within the phylum Spirochaetes and the order Spirochaetales. B. miyamotoi is spirochete from the relapsing fever (RF) group of Borrelia. In RF-Borrelia complex only B. miyamotoi is transmitted by Ixodes ticks - a vector of B. burgdorferi s.l. complex. The biological feature that distinguishes B. miyamotoi from B. burgdorferi s.l. is transovarial transmission. B. miyamotoi was first isolated from questing I. persulcatus ticks and mouse Apodemus argentus in Japan in 1994. The main vector of B. miyamotoi is I. persulcatus (Asia), I. pacificus, I. scapularis (North America), and I. ricinus (Europe). Worldwide, B. miyamotoi prevalence in questing Ixodes ticks ranges from 0.2 to 10%. A phylogenetic analysis based on selected sequences of B. miyamotoi genome revealed genetic differences between isolates from Asia, North America, and Europe, which are clearly separated into three genotypes. Human symptomatic cases of Borrelia miyamotoi disease (BMD) were first reported in 2011 in Russia and then in North America, Europe, and Asia. BMD is usually manifested by several episodes of fever and flu-like symptoms (chills, headaches, muscle, and joint aches and general fatigue). However, serious symptoms such as meningoencephalitis can be observed.
In Europe, tick-borne diseases transmitted by
are the most common zoonoses with significant medical and veterinary importance[1]. This hematophagous arthropod is a reservoir and vector of many pathogenic microorganisms, including the bacteria
sensu lato (s.l.) complex—the causative agent of Lyme borreliosis (LB),
spp., and
spp., as well as the flavivirus responsible for tick-borne encephalitis (TBE) and the etiological protozoan agents of babesiosis[2][3]. With advanced methods of molecular biology, new tick-borne microorganism species and their genetic variants with confirmed or potential pathogenicity for humans and animals are still being identified[4]. One of the emerging
-borne diseases in the northern temperate climate zones of the world, including Europe, is
disease (BMD), caused by spirochete from the relapsing fever (RF) group of
was first isolated from questing
ticks and mouse
in Japan[7], it was considered to be a non-pathogenic endosymbiont. However, since 2011 many symptomatic
infections in humans have been noted in Asia, North America, and Europe [8][9][10][11][12][13][14].
is a Gram-negative bacteria included in the genus
from the family
, within the phylum
and the order
[15].
species are obligate parasites, transmitted by arthropod vectors to vertebrate hosts. The biological feature that distinguishes
and several other relapsing fever species from
s.l. is transovarial transmission[16].
The
spirochete cells are 0.2–0.5 mm in diameter by 3–30 mm in length, with 15–20 periplasmic flagella (endoflagella) located in the periplasmic space between the outer membrane and the protoplasmic cylinder. These cells can move actively with frequent reversal of direction [15][17]. Due to limited
biosynthetic potential, its in vitro culture is difficult (as other
species) and requires microaerophilic conditions and complex nutrition. However, it can be propagated in Kelly-Pettenkofer medium with fetal calf serum (MKP-F) [18].
Although the
species share spirochetal morphology, they have different biological, clinical, and epidemiological features. Based on their arthropod vectors and genetic characteristics two major groups of
were distinguished. The first group contains 20
species, including the
s.l. complex, an agent of LB, and are transmitted by
hard ticks. The second group includes 25
species associated with human RF and mostly found in soft ticks (
) but also in lice (
) and hard ticks (
,
,
). In RF-
complex only
is transmitted by
ticks—a vector of
s.l. complex [15][19][20]. These two groups are genetically similar but form distinct, independent monophyletic clades and share a common ancestor. In 2014, Adeolu and Gupta[21] proposed splitting the spirochetes from the genus
into two separate genera: a novel genus,
gen. nov., containing the causative agents of Lyme disease and a revised genus
, with spirochetes causing RF, including
. However, the proposed change in the name of this pathogenic bacteria species proved controversial and did not receive support among scientists, clinicians or public health authorities, who felt it would lead to confusion and pose a risk to patient safety [20][22][23].
The first information about the organization of the
genome and its differences in relation to the known species from the LB- and RF-
groups was published in 1995[7]. Later, more advanced molecular analysis of Asian, American, and European
isolates from
ticks and clinical samples revealed the complexity of the genome structure typical of
spirochetes[24][25][26][27][28][29]. However, the most information was obtained by sequencing the genome of
Izh-4 isolate from a Russian patient[30]. The complete genome of a single
cell consists of one linear chromosome (~900 kb) and 12 linear and two circular plasmids (from 6 to 73 kb). Two of the plasmids (lp70 and lp64) had not previously been found in other
species. A total of 1362 genes, including 1222 protein-coding genes, 103 pseudogenes, 31 genes for transfer RNA (tRNA), a cluster of three genes of ribosomal RNA (rRNA), and three genes of non-coding RNA (ncRNA) were identified. In
virulence, a significant role is played by plasmid lp4, which includes genes of variable membrane proteins (VMPs), necessary to mask the bacteria from the host immune system and prolong the infection[30][31][32]. A comparison of different
isolates revealed that the number and order of VMPs genes were unique for each of them[30].
Phylogenetic analysis based on genome sequences of
showed genetic differences between isolates from Asia, North America and Europe which are clearly separated into three types (genotypes) and form a monophyletic clade inside the RF-
spirochetes[30]. However, the genetic differences between the
isolates are probably not connected with geographic origin, but rather with pathogenicity, vector competence, and host range[16[24].
The
genetic distance from other LB species and the relationship with the species from the RF group is evidenced by the carriage and expression of a
gene, coding the immunoreactive protein glycerophosphodiester phosphodiesterase [33][34]. The
gene and GlpQ protein are conserved among the members of the genus
, except LB spirochetes (
). Therefore, GlpQ is usually used as a marker in molecular and serological tests to detect RF spirochete infections and to distinguish cases of LB and other tick-borne infections (e.g., anaplasmosis, babesiosis) [8][35][36][37].
Molecular relationships between
and other RF
species based on the sequences of the
gene selected from GenBank. The consensus tree constructed using the neighbor-joining method and the maximum composite likelihood as the distance method; numbers at the tree nodes indicate bootstrap value from 1000 replicates; analyses were conducted in MEGA X[38]. Marks: orange—European type, green—Asian type, red—American type
. The genus names of the vectors were added.