Bor.rel.i.a.ce'ae. N.L. fem. n.Borreliatype genus of the family; suff. ‐aceaeending to denote a family; N.L. fem. pl. n.Borreliaceae, the family ofBorrelia. Spirochaetes / Spirochaetia / Spirochaetales / Borreliaceae Cells are helical with regular or irregular coils, 0.2–0.3 µm in diameter and 10–40 µm in length. Cells do not have hooked ends. Motile. Inner and outer membrane with periplasmic flagella with 7–20 subterminal insertion points. Aniline‐stain‐positive. Microaerophilic. Most members of the family cultivable in complex media that includesN‐acetylglucosamine. Optimum growth between 33°C and 38°C. Diamino acid of peptidoglycan is ornithine. Lacks a lipopolysaccharide. Linear chromosome and plasmids with hairpin telomeres. The family currently accommodates the generaBorreliaandBorreliella. Members of the family are host‐associated organisms that are transmitted between vertebrate reservoirs by a hematophagous arthropod, in all but one case, a tick. Members include the agents of relapsing fever, Lyme disease, and avian spirochetosis. DNA G + C content (mol%): 26–30. Type genus:BorreliaSwellengrebel 1907, 562AL.

The discovery of Borrelia species that were related to the agents of relapsing fever but were transmitted by hard ticks rather than soft ticks challenged previous taxonomies based largely on microbe-host specificities and geographic considerations. One of these newly-identified organisms is the Borrelia miyamotoi sensu lato strain LB-2001 from North America and transmitted by Ixodes scapularis. This or related strains have been identified as the cause of human disease, but comparatively little is known about their biology or genetics. Using recently acquired chromosome sequence of LB-2001 together with database sequences and additional sequences determined here, I carried out comparisons of the several species of Borrelia, including those in the two major clades: the relapsing fever group of species and the Lyme disease group of species. Phylogenetic inference at the species level was based on four data sets: whole chromosomes of ∼1Mb each, and concatenated sequences of 19 ribosomal protein genes, 3 conserved nucleic acid enzymes (rpoC, recC, and dnaE), and 4 contiguous genes for nucleotide salvage on a large plasmid. Analyses using neighbor-joining, maximum likelihood, and Bayesian methods were largely concordant for each of the trees. They showed that LB-2001 and related hard tick-associated organisms, like Borrelia lonestari, are deeply positioned within the RF group of species and that these organisms did not, as some earlier estimations had suggested, constitute a paraphyletic group. The analyses also provided further evidence that major changes in host ranges and life cycles, such as hard to soft ticks or vice versa, may not correlate well with overall sequence differences. The genetic differences between LB-2001 and B. miyamotoi sensu stricto justify provisional use of the "sensu lato" designation for LB-2001.

The zoonotic pathogen Borrelia hermsii bears its multiple paralogous genes for variable antigens on several linear plasmids. Application of combined long-read and short-read next-generation sequencing provided complete sequences for antigen-encoding plasmids as well as other linear and circular plasmids and the linear chromosome of the genome.

The widely-distributed North American species Peromyscus leucopus and P. maniculatus of cricetine rodents are, between them, important natural reservoirs for several zoonotic diseases of humans: Lyme disease, human granulocytic anaplasmosis, babesiosis, erhlichiosis, hard tickborne relapsing fever, Powassan virus encephalitis, hantavirus pulmonary syndrome, and plague. While these infections are frequently disabling and sometimes fatal for humans, the peromyscines display little pathology and apparently suffer few consequences, even when prevalence of persistent infection in a population is high. While these Peromyscus spp. are unable to clear some of the infections, they appear to have partial resistance, which limits the burden of the pathogen. In addition, they display traits of infection tolerance, which reduces the damage of the infection. Research on these complementary resistance and tolerance phenomena in Peromyscus has relevance both for disease control measures targeting natural reservoirs and for understanding the mechanisms of the comparatively greater sickness of many humans with these and other infections.

Borrelia burgdorferi, an emerging bacterial pathogen, is maintained in nature by transmission from one vertebrate host to another by ticks. One of the few antigens against which mammals develop protective immunity is the highly polymorphic OspC protein, encoded by the ospC gene on the cp26 plasmid. Intragenic recombination among ospC genes is known, but the extent to which recombination extended beyond the ospC locus itself is undefined. We accessed and supplemented collections of DNA sequences of ospC and other loci from ticks in three U. S. regions (the Northeast, the Midwest, and northern California); a total of 839 ospC sequences were analyzed. Three overlapping but distinct populations of B. burgdorferi corresponded to the geographic regions. In addition, we sequenced 99 ospC flanking sequences from different lineages and compared the complete cp26 sequences of 11 strains as well as the cp26 bbb02 loci of 56 samples. Besides recombinations with traces limited to the ospC gene itself, there was evidence of lateral gene transfers that involved (i) part of the ospC gene and one of the two flanks or (ii) the entire ospC gene and different lengths of both flanks. Lateral gene transfers resulted in different linkages between the ospC gene and loci of the chromosome or other plasmids. By acquisition of the complete part or a large part of a novel ospC gene, an otherwise adapted strain would assume a new serotypic identity, thereby being comparatively fitter in an area with a high prevalence of immunity to existing OspC types. IMPORTANCE The tick-borne zoonosis Lyme borreliosis is increasing in incidence and spreading geospatially in North America. Further understanding of the evolution and genetics of its cause, Borrelia burgdorferi, in its environments fosters progress toward ecologically based control efforts. By means of DNA sequencing of a large sample collection of the pathogen from across the United States, we studied the gene for the bacterium's highly diverse OspC protein, protective immunity against which develops in animals. We found that the distributions and frequencies of types of OspC genes differed between populations of B. burgdorferi in the Northeast, the Midwest, and California. Over time, OspC genes were transferred between strains through recombinations involving the whole or parts of the gene and one or both flanks. Acquisitions of OspC genes that are novel for the region confer to recipients unique identities to host immune systems and, presumably, selective advantage when immunity to existing types is widespread among hosts.

Peromyscus leucopus, the white-footed mouse, is one of the more abundant mammals of North America and is a major reservoir host for at least five tickborne diseases of humans, including Lyme disease and a newly-recognized form of relapsing fever. In comparison to Mus musculus, which is not a natural reservoir for any of these infections, there has been little research on experimental infections in P. leucopus. With the aim of further characterizing the diversity of phenotypes of host responses, we studied a selection of quantitative traits in colony-bred and -reared outbred P. leucopus adults that were uninfected, infected with the relapsing fever agent Borrelia hermsii alone, or infected after immunization with Lyme disease vaccine antigen OspA and keyhole limpet hemocyanin (KLH). The methods included measurements of organ weights, hematocrits, and bleeding times, quantitative PCR for bacterial burdens, and enzyme immunoassays for serum antibodies against both the immunization proteins and cellular antigens of the infecting organism. The results included the following: (i) uninfected animals displayed wide variation in relative sizes of their spleens and in their bleeding times. (ii) In an experiment with matched littermates, no differences were observed between females and males at 7 days of infection in bacterial burdens in blood and spleen, relative spleen size, or antibody responses to the B. hermsii specific-antigen, FbpC. (iii) In studies of larger groups of males or females, the wide variations between bacterial burdens and in relative spleen sizes between individuals was confirmed. (iv) In these separate groups of males and females, all animals showed moderate-to-high levels of antibodies to KLH but wide variation in antibody levels to OspA and to FbpC. The study demonstrated the diversity of host responses to infection and immunization in this species and identified quantitative traits that may be suitable for forward genetics approaches to reservoir-pathogen interactions.