The North American deermouse Peromyscus leucopus is reservoir for several zoonotic agents, including bacterial, protozoan, and viral. It is remarkable for indiscernible or limited fitness consequences of these infections, a trait known as infection tolerance. But experimental infections have largely been of pathogens that P. leucopus naturally harbors. We asked whether infection tolerance extended to an agent, like SARS-CoV-2 virus, it had presumably not encountered before. Following protocols for experiments with mice and hamsters, we infected 8 female and 8 male P. leucopus of heterogeneous stock and compared responses of these animals on days 3 or 6 to those of 14 controls inoculated with virus-free medium. Serologic and virologic confirmation of infection was obtained for all exposed deermice. Moderate inflammation in lungs was histologically evident in infected animals, but no histological changes were noted in brains, even when viral RNA was present. Fourteen (88%) animals displayed no or only mild sickness; two had more severe illness. Genome-wide RNA-seq revealed an interferon-stimulated response on day 3 superceded mainly by a cell-mediated response by day 6. In brains transcription of the interferon-stimulated genes Isg15 and Mx2 positively correlated with viral RNA levels. The findings confirmed susceptibility of this species of Peromyscus to SARS-CoV-2 virus. For most infected outbred animals the immune response was swift and effective in controlling the pathogen and without evidence of excessive inflammation. Whatever is the basis for P. leucopus' trait of infection tolerance, it extended to at least one pathogen that for it would be novel. Importance:Peromyscus leucopus is North American rodent that is reservoir for several agents of human disease, while exhibiting minimal illness, a phenotype termed infection tolerance. Whether this trait is pathogen-specific or represents a broader strategy has remained uncertain. By experimentally infecting P. leucopus with SARS-CoV-2 virus, which it is unlikely to have encountered, we investigated whether infection tolerance extends to a novel virus. Despite disseminated infection and lung pathology, most animals showed only mild or no disease. Expression analyses revealed early interferon-stimulated responses followed by cell-mediated responses with only limited production of inflammatory mediators interferon-gamma and nitric oxide synthase 2. Compared with results with a mouse model of infection, deermice displayed higher baseline expression of antiviral genes and quicker resolution of interferon responses. These findings suggest that infection tolerance is a strategy that limits immunopathology generally while resisting microbes, which has implications for understanding reservoir competence and host resilience.

Borrelia miyamotoi is an emerging relapsing fever spirochete transmitted by Ixodes spp. ticks that serve as vectors for other human pathogens, including the agents of Lyme disease. To date, an animal model to study tick-borne B. miyamotoi infection and pathology has not been reported. Here, we describe the development of a laboratory mouse model of infection using clinical isolate CT14D4 derived from the blood of a Connecticut resident with disseminated Lyme disease. Genomic analysis revealed that the CT14D4 genome was similar to other B. miyamotoi strains isolated from Ixodes scapularis ticks in the eastern United States. We show that CT14D4 can be propagated in mice by needle inoculation and through a tick-mouse infection cycle. Relapsing spirochetemia was observed in wild-type (WT), Myd88 -/-, and splenectomized mice, all of which eventually cleared the infections. In contrast, Rag1 -/- mice lacking B and T cells remain persistently bacteremic. WT mice that had cleared CT14D4 infection are resistant to reinfection with this B. miyamotoi strain. Spirochetes were visualized in several organs after perfusion fixation of infected Rag1 -/- mice, including the brain, with histopathology revealing extramedullary hematopoiesis and inflammatory infiltrates that were most pronounced in the liver. WT mice exhibited similar but milder pathology during periods of bacteremia. These studies provide a useful model to study hard-tick relapsing fever pathogenesis and disease.

X-chromosome inactivation (XCI) equalizes X-linked gene dosage between XX females and XY males in eutherian mammals and is canonically initiated by the long noncoding RNA Xist , which coats one X chromosome and recruits Polycomb-mediated chromatin silencing. Xist expression has therefore been considered female-specific and central to balancing gene dosage between two X chromosomes in females and a single X chromosome in males. However, emerging evidence suggests that Xist can also be expressed in male cells in both healthy and pathogenic contexts, raising fundamental questions about the scope and constraints of Xist function. Here, we identify robust Xist expression in somatic cells of male white-footed deermice ( Peromyscus leucopus ), a placental mammal with a conventional XY karyotype. Unlike the chromosome-wide Xist RNA coating observed in females, male Xist RNA localizes as discrete nuclear puncta and is detected across multiple tissues by RNA-seq, RT-qPCR, and RNA fluorescence in situ hybridization. Integrative transcriptomic and chromatin profiling using CUT&Tag and single-nucleus Paired-Tag reveals that male Xist expression is not merely incidental but has measurable regulatory consequences. In females, Xist expression is associated with chromosome-wide enrichment of the repressive histone mark H3K27me3 and transcriptional silencing of X-linked genes. In males, although Xist transcription is also associated with H3K27me3, this interaction does not induce global X-chromosome inactivation. Instead, Xist selectively represses a subset of dosage-sensitive neural and mitochondrial X-linked genes, while the majority of X-linked genes remain largely active. Notably, with persistent Xist activity, neither males nor females achieve complete X-to-autosome dosage compensation in P. leucopus . These findings establish P. leucopus as a mammalian system in which male Xist operates outside the canonical female-specific XCI pathway, revealing a gene-selective model of X-chromosome regulation. Our results challenge the universality of prevailing XCI models and suggest that partial, context-dependent Xist activity represents a viable and evolutionarily stable dosage compensation strategy in mammals. Author Summary:In mammals, females and males differ in their sex chromosome: females have two X chromosomes, while males have one. This difference creates a potential imbalance in gene dosage, which can disrupt development if not properly controlled. Typically, females compensate by turning off one chromosome through a process called X-chromosome inactivation (XCI), which is triggered by the long noncoding RNA Xist . In parallel, a process known as X-to-autosome dosage compensation balances X-linked gene expression relative to the rest of the genome. Because XCI occurs in females, Xist has long been considered to function only in female cells and be inactive in males. Here, we show that Xist is persistently expressed in male white-footed deermice ( Peromyscus leucopus ), a cricetid rodent with a conventional XY sex chromosome system. Unlike the large Xist RNA "cloud" that covers the inactive X chromosome in females, Xist RNA in males appears as small, discrete spots in the nucleus. By combining gene expression and chromatin profiling, we find that male Xist associates with the repressive histone mark H3K27me3 but does not switch off the entire X chromosome. Instead, Xist in males selectively reduces the activity of a limited set of X-linked genes, while most X-linked genes remain active. Surprisingly, we also find that neither male nor female P. leucopus achieves complete balance between X-linked and autosomal gene expression, despite the long-held view that such balance is essential for mammalian viability. By uncovering functional Xist activity in males of a non-model species and demonstrating incomplete dosage compensation in both sexes, this work challenges the traditional view of XCI as a strictly female-specific strategy and reveals an unexpected flexibility in how mammals regulate the X chromosome.

IntroductionThe white-footed deermouse Peromyscus leucopus is a primary reservoir for the agents of Lyme disease and other zoonoses in North America and manifests infection tolerance for the bacteria, protozoa, and viruses it hosts. In previous in vivo studies, P. leucopus and Mus musculus differed in the degree of sickness and profiles of biomarkers after exposure to a bacterial lipopolysaccharide, a TLR4 agonist. MethodsAs an approach for assessing immunity of mammals in nature and for longitudinal studies of colony animals in the laboratory, we evaluated primary dermal fibroblast cultures of P. leucopus and M. musculus in their short-term responses to a TLR2 agonist lipopeptide using bulk and single-cell RNA-seq. ResultsBy single-cell RNA-seq, cultures of both species comprised at least two types of fibroblasts, which were further differentiated in their responses to TLR agonists. With continued passage, the mouse cell population lost viability, while the deermouse cell population spontaneously transformed into a cell line stably maintained under standard conditions. Bulk RNA-seq revealed distinctive profiles for deermouse and mouse cells in arginine metabolism gene expression, high baseline transcription of the antioxidant transcription factor Nfe2l2 (Nrf2) in deermouse fibroblasts, and the transcription of the aging-associated cytokine interleukin-11 in agonist-treated mouse fibroblasts but not deermouse fibroblasts. In the cultures of both species, there was increased transcription of several types of endogenous retrovirus (ERV) and transposable elements (TEs) after exposure to the agonist. The transcribed ERV/TE sequences in M. musculus cells were generally longer in length and had greater potential for translation than sequences in treated P. leucopus cells. DiscussionThe results indicate the feasibility of this in vitro model for both laboratory- and field-based studies, and that inherent differences between deer mice and mice in cell-autonomous innate immune responses and ERV/TE activation can be demonstrated in dermal fibroblasts as well as the animals themselves.

This chapter provides an update on current understanding of the biology and genetics of the agents of Lyme disease (or Lyme borreliosis). The Lyme disease agents have hitherto been categorized under the umbrella term 'Borrelia burgdorferi sensu lato'. This expediently served to distinguish them from other Borrelia species, such as the several species that cause relapsing fever. This chapter recognizes the distinctiveness of this group by accepting the assignment of 'B. burgdorferi sensu lato' species to the new genus Borreliella ('Borrelia-like'). This chapter is divided into sections that provide detailed information on the following: the distinct biological and genetic features of B. burgdorferi compared to other bacteria; the pathogenesis of B. burgdorferi infection in humans and other mammals; the inability of B. burgdorferi to grow inside mammalian cells; the role of B. burgdorferi, B. afzelii and B. garinii as major causes of Lyme disease in the world; the differences between these 3 species in the manifestations of infection; available genotypic methods for distinguishing different strains of B. burgdorferi; laboratory challenges in culturing B. burgdorferi isolates; the clinical significance of morphologic variants of spirochetes under adverse conditions (e.g. exposure to antibiotics); the antibiotic susceptibility of B. burgdorferi; and whether B. burgdorferi forms biofilms.

The white-footed deermouse Peromyscus leucopus , a long-lived rodent, is a key reservoir in North America for agents of several zoonoses, including Lyme disease, babesiosis, anaplasmosis, and a viral encephalitis. While persistently infected, this deermouse is without apparent disability or diminished fitness. For a model for inflammation elicited by various pathogens, the endotoxin lipopolysaccharide (LPS) was used to compare genome-wide transcription in blood by P. leucopus , Mus musculus, and Rattus norvegicus and adjusted for white cell concentrations. Deermice were distinguished from the mice and rats by LPS response profiles consistent with non-classical monocytes and alternatively-activated macrophages. LPS-treated P. leucopus , in contrast to mice and rats, also displayed little transcription of interferon-gamma and lower magnitude fold-changes in type 1 interferon-stimulated genes. These characteristics of P. leucopus were also noted in a Borrelia hermsii infection model. The phenomenon was associated with comparatively reduced transcription of endogenous retrovirus sequences and cytoplasmic pattern recognition receptors in the deermice. The results reveal a mechanism for infection tolerance in this species and perhaps other animal reservoirs for agents of human disease.

The abundant and widely distributed deermice Peromyscus leucopus and P. maniculatus are important reservoirs for several different zoonotic agents in North America. For the pathogens they persistently harbor, these species are also examples of the phenomenon of infection tolerance. In the present study a prior observation of absent expression of the high-affinity Fc immunoglobulin gamma receptor I (FcγRI), or CD64, in P. leucopus was confirmed in an experimental infection with Borreliella burgdorferi, a Lyme disease agent. We demonstrate that the null phenotype is attributable to a long-standing inactivation of the Fcgr1 gene in both species by a deletion of the promoter and coding sequence for the signal peptide for FcγRI. The Fcgr1 pseudogene was also documented in the related species P. polionotus. Six other Peromyscus species, including P. californicus, have coding sequences for a full-length FcγRI, including a consensus signal peptide. An inference from reported phenotypes for null Fcgr1 mutations engineered in Mus musculus is that one consequence of pseudogenization of Fcgr1 is comparatively less inflammation during infection than in animals, including humans, with undisrupted, fully active genes.

The white-footed deermouse Peromyscus leucopus, a long-lived rodent, is a key reservoir for agents of several zoonoses, including Lyme disease. While persistently infected, this deermouse is without apparent disability or diminished fitness. For a model for inflammation elicited by various pathogens, the endotoxin lipopolysaccharide (LPS) was used to compare genome-wide transcription in blood by P. leucopus, Mus musculus and Rattus norvegicus and adjusted for white cell concentrations. Deermice were distinguished from the mice and rats by LPS response profiles consistent with non-classical monocytes and alternatively-activated macrophages. LPS-treated P. leucopus, in contrast to mice and rats, also displayed little transcription of interferon-gamma and lower magnitude fold-changes in type 1 interferon-stimulated genes. This was associated with comparatively reduced transcription of endogenous retrovirus sequences and cytoplasmic pattern recognition receptors in the deermice. The results reveal a mechanism for infection tolerance in this species and perhaps other animal reservoirs for agents of human disease.

BACKGROUND Autoimmune diseases often have strong genetic associations with specific HLA-DR alleles. The synovial lesion in chronic inflammatory forms of arthritis shows marked upregulation of HLA-DR molecules, including in postinfectious Lyme arthritis (LA). However, the identity of HLA-DR–presented peptides, and therefore the reasons for these associations, has frequently remained elusive.METHODS Using immunopeptidomics to detect HLA-DR–presented peptides from synovial tissue, we identified T cell epitopes from 3 extracellular matrix (ECM) proteins in patients with postinfectious LA, identified potential Borreliella burgdorferi–mimic (Bb-mimic) epitopes, and characterized T and B cell responses to these peptides or proteins.RESULTS Of 24 postinfectious LA patients, 58% had CD4+ T cell responses to at least 1 epitope of 3 ECM proteins, fibronectin-1, laminin B2, and/or collagen Vα1, and 17% of 52 such patients had antibody responses to at least 1 of these proteins. Patients with autoreactive T cell responses had significantly increased frequencies of HLA-DRB1*04 or -DRB1*1501 alleles and more prolonged arthritis. When tetramer reagents were loaded with ECM or corresponding Bb-mimic peptides, binding was only with the autoreactive T cells. A high percentage of ECM-autoreactive CD4+ T cells in synovial fluid were T-bet–expressing Th1 cells, a small percentage were RoRγt-expressing Th17 cells, and a minimal percentage were FoxP3-expressing Tregs.CONCLUSION Autoreactive, proinflammatory CD4+ T cells and autoantibodies develop to ECM proteins in a subgroup of postinfectious LA patients who have specific HLA-DR alleles. Rather than the traditional molecular mimicry model, we propose that epitope spreading provides the best explanation for this example of infection-induced autoimmunity.FUNDING Supported by National Institute of Allergy and Infectious Diseases R01-AI101175, R01-AI144365, and F32-AI125764; National Institute of Arthritis and Musculoskeletal and Skin Diseases K01-AR062098 and T32-AR007258; NIH grants P41-GM104603, R24-GM134210, S10-RR020946, S10-OD010724, S10-OD021651, and S10-OD021728; and the G. Harold and Leila Y. Mathers Foundation, the Eshe Fund, and the Lyme Disease and Arthritis Research Fund at Massachusetts General Hospital.

Although Peromyscus leucopus (deermouse) is not considered a genetic model system, its genus is well suited for addressing several questions of biologist interest, including the genetic bases of longevity, behavior, physiology, adaptation, and it’s ability to serve as a disease vector. Here we explore a diversity outbred approach for dissecting complex traits in Peromyscus leucopus , a non-traditional genetic model system. We take advantage of a closed colony of deer-mice founded from 38 individuals between 1982 and 1985 and subsequently maintained for 35+ years (∼40-60 generations). From 405 low-pass (∼1X) short-read sequenced deermice we accurately imputed genotypes at 17,751,882 SNPs. Conditional on observed genotypes for a subset of 297 individuals, simulations were conducted in which a QTL contributes 5% to a complex trait under three different genetic models. The power of either a haplotype- or marker-based statistical test was estimated to be 15-25% to detect the hidden QTL. Although modest, this power estimate is consistent with that of DO/HS mice and rat experiments for an experiment with ∼300 individuals. This limitation in QTL detection is mostly associated with the stringent significance threshold required to hold the genome-wide false positive rate low, as in all cases we observe considerable linkage signal at the location of simulated QTL, suggesting a larger panel would exhibit greater power. For the subset of cases where a QTL was detected, localization ability appeared very desirable at ∼1-2Mb. We finally carried out a GWAS on a demonstration trait, bleeding time. No tests exceeded the threshold for genome-wide significance, but one of four suggestive regions co-localizes with Von Willebrand factor. Our work suggests that complex traits can be dissected in founders-unknown P. leucopus colony mice in much the same manner as founders-known DO/HS mice and rats, with genotypes obtained from low pass sequencing data. Our results further suggest that the DO/HS approach can be powerfully extended to any system in which a founders-unknown closed colony has been maintained for several dozen generations.

Spirochetes of the family Borreliaceae are, with one exception, tick-borne pathogens of a variety of vertebrates. The family at present comprises two genera: Borrelia (Swellengrebel), which includes the agents of relapsing fever, avian spirochetosis, and bovine borreliosis, and Borreliella (Gupta et al.), which includes the agents of Lyme disease and was formerly known as 'Borrelia burgdorferi sensulato complex'. The two genera are distinguished not only by their disease associations but also biological features in the tick vector, including tissue location in unfed ticks and transovarial transmission. Borrelia species transmitted by argasid (soft) ticks tend to have more exclusive relationships with their tick vectors than do other Borrelia species and all Borreliella species that have ixodid (hard) ticks as vectors. The division of genera is supported by phylogenomic evidence from whole genomes and by several specific molecular markers. These distinguishing phylogenetic criteria also applied to three new species or isolates of Borrelia that were discovered in ixodid ticks of reptiles, a monotreme, and birds. Although the deep branching of the family from other spirochetes has been a challenge for inferences about evolution of the family, the discovery of related microorganisms in the gut microbiota of other arachnids suggests an ancestral origin for the family as symbionts of ticks and other arachnids.

Animals that are natural carriers of pathogens that cause human diseases commonly manifest little or no sickness as a consequence of infection. Examples include the deer mouse, Peromyscus leucopus , which is a reservoir for Lyme disease and several other disease agents in North America, and some types of bats, which are carriers of viruses with pathogenicity for humans.

ABSTRACT Animals that are competent natural reservoirs of zoonotic diseases commonly suffer little morbidity from the pathogens they persistently harbor. The mechanisms of this infection tolerance and the trade-off costs are poorly understood. We used exposure to a single dose of lipopolysaccharide (LPS) endotoxin as an experimental model of inflammation to compare the responses of the cricentine rodent Peromyscus leucopus , the white-footed deermouse, to that of Mus musculus , the standard laboratory model for pathogenesis studies. Four hours after injection with either LPS or saline, blood and spleen and liver tissues were collected postmortem and subjected to RNA-seq, untargeted metabolomics, and specific RT-qPCR. This was followed by analysis of differential expression at the gene, pathway, and empirical network levels. The deermice showed the same signs of sickness as the mice with LPS exposure, and in addition demonstrated comparable increases in levels of corticosterone and expression of interleukin (IL)-6, tumor necrosis factor, IL-1β, and acute phase reactants, including C-reactive protein. But whereas the M. musculus response to LPS was best-characterized by network analysis as cytokine-associated, the P. leucopus response was dominated by pathway terms associated with neutrophil activity. Dichotomies between the species in expression profiles of arginase 1 and nitric oxide synthase 2, as well as the ratios of IL-10 to IL-12, were consistent with a type M1 polarized macrophage response in the mice and a type M2 or alternatively-activated response in the deermice. Analysis of metabolites in the plasma and RNA in the tissues revealed differences between the two species in tryptophan metabolism during response to LPS. Two up-regulated genes in particular signified the difference between the species: Slpi (secretory leukocyte proteinase inhibitor) and Ibsp (integrin-binding protein sialoprotein). The latter was previously unrecognized in the context of inflammation or infection. Key RNA-seq findings in P. leucopus were replicated in a second LPS experiment with older animals, in a systemic bacterial infection model, and with cultivated fibroblasts. Taken together, the results indicate that the deermouse possesses several adaptive traits to moderate effects of inflammation and oxidative stress ensuing from infection. This seems to be at the cost of infection persistence and that is to the benefit of the pathogen.

The cricetine rodent Peromyscus leucopus is an important reservoir for several human zoonoses, including Lyme disease, in North America. Akin to hamsters, the white-footed deermouse has been unevenly characterized in comparison to the murid Mus musculus . To further understanding of P. leucopus ’ total genomic content, we investigated gut microbiomes of an outbred colony of P. leucopus , inbred M. musculus , and a natural population of P. leucopus . Metagenome and whole genome sequencing were combined with microbiology and microscopy approaches. A focus was the genus Lactobacillus , four diverse species of which were isolated from forestomach and feces of colony P. leucopus . Three of the species-- L. animalis , L. reuteri , and provisionally-named species “L. peromysci”--were identified in fecal metagenomes of wild P. leucopus but not discernibly in samples from M. musculus . L. johnsonii , the fourth species, was common in M. musculus but absent or sparse in wild P. leucopus . Also identified in both colony and natural populations were a Helicobacter sp. in feces but not stomach, and a Tritrichomonas sp. protozoan in cecum or feces. The gut metagenomes of colony P. leucopus were similar to those of colony M. musculus at the family or higher level and for major subsystems. But there were multiple differences between species and sexes within each species in their gut metagenomes at orthologous gene level. These findings provide a foundation for hypothesis-testing of functions of individual microbial species and for interventions, such as bait vaccines based on an autochthonous bacterium and targeting P. leucopus for transmission-blocking.

The western blacklegged tick, Ixodes pacificus, an important vector in the western United States of two zoonotic spirochetes: Borrelia burgdorferi (also called Borreliella burgdorferi), causing Lyme disease, and Borrelia miyamotoi, causing a relapsing fever-type illness. Human cases of Lyme disease are well-documented in California, with increased risk in the north coastal areas and western slopes of the Sierra Nevada range. Despite the established presence of B. miyamotoi in the human-biting I. pacificus tick in California, clinical cases with this spirochete have not been well studied. To assess exposure to B. burgdorferi and B. miyamotoi in California, and to address the hypothesis that B. miyamotoi exposure in humans is similar in geographic range to B. burgdorferi, 1,700 blood donor sera from California were tested for antibodies to both pathogens. Sampling was from high endemic and low endemic counties for Lyme disease in California. All sera were screened using the C6 ELISA. All C6 positive and equivocal samples and nine randomly chosen C6 negative samples were further analyzed for B. burgdorferi antibody using IgG western blot and a modified two ELISA test system and for B. miyamotoi antibody using the GlpQ ELISA and B. miyamotoi whole cell sonicate western blot. Of the 1,700 samples tested in series, eight tested positive for antibodies to B. burgdorferi (0.47%, Exact 95% CI: 0.20, 0.93) and two tested positive for antibodies to B. miyamotoi (0.12%, Exact 95% CI: 0.01, 0.42). There was no statistically significant difference in seroprevalence for either pathogen between high and low Lyme disease endemic counties. Our results confirm a low frequency of Lyme disease and an even lower frequency of B. miyamotoi exposure among adult blood donors in California; however, our findings reinforce public health messaging that there is risk of infection by these emerging diseases in the state.

The cricetine rodents Peromyscus leucopus and P. maniculatus are key reservoirs for several zoonotic diseases in North America. We determined the complete circular mitochondrial genome sequences of representatives of 3 different stock colonies of P. leucopus, one stock colony of P. maniculatus and two wild populations of P. leucopus. The genomes were syntenic with that of the murids Mus musculus and Rattus norvegicus. Phylogenetic analysis confirmed that these two Peromyscus species are sister taxa in a clade with P. polionotus and also uncovered a distinction between P. leucopus populations in the eastern and the central United States. In one P. leucopus lineage four extended regions of mitochondrial pseudogenes were identified in the nuclear genome. RNA-seq analysis revealed transcription of the entire genome and differences from controls in the expression profiles of mitochondrial genes in the blood, but not in liver or brain, of animals infected with the zoonotic pathogen Borrelia hermsii. PCR and sequencing of the D-loop of the mitochondrion identified 32 different haplotypes among 118 wild P. leucopus at a Connecticut field site. These findings help to further establish P. leucopus as a model organism for studies of emerging infectious diseases, ecology, and in other disciplines.

The rodent Peromyscus leucopus is the natural reservoir of several tick-borne infections, including Lyme disease. To expand the knowledge base for this key species in life cycles of several pathogens, we assembled and scaffolded the P. leucopus genome. The resulting assembly was 2.45 Gb in total length, with 24 chromosome-length scaffolds harboring 97% of predicted genes. RNA sequencing following infection of P. leucopus with Borreliella burgdorferi , a Lyme disease agent, shows that, unlike blood, the skin is actively responding to the infection after several weeks. P. leucopus has a high level of segregating nucleotide variation, suggesting that natural resistance alleles to Crispr gene targeting constructs are likely segregating in wild populations. The reference genome will allow for experiments aimed at elucidating the mechanisms by which this widely distributed rodent serves as natural reservoir for several infectious diseases of public health importance, potentially enabling intervention strategies.

Vancomycin is active in vitro and in vivo in mouse systems against Lyme disease borrelia; however, there are no published data on the efficacy of vancomycin in patients with Lyme disease and no convincing theoretical advantages of vancomycin over the currently used and highly effective orally administered antimicrobial agents, including doxycycline, amoxicillin and cefuroxime axetil. In addition, vancomycin may cause a wide variety of potentially serious adverse effects and requires the placement of an intravenous catheter. It is concluded that vancomycin is a much less attractive option for the treatment of patients with early Lyme disease (or any other manifestation of Lyme disease), compared with the antimicrobials currently being used. Based on available evidence, clinical studies to evaluate the safety and efficacy of vancomycin for Lyme disease cannot be recommended.

Abstract Bor.rel.i.el'la. N.L. fem. dim. n. Borreliella named after Amédée Borrel (1867–1936). Spirochaetes / Spirochaetes / Spirochaetales / Borreliaceae / Borreliella Cells are helical, 0.2–0.3 µm in diameter, 15–30 µm in length, and do not have hooked ends. Coils are regular or irregular in spacing and amplitude. Motile. Inner and outer membranes with overlapping periplasmic flagella; 7–11 subterminal insertion points in most species. Aniline‐stain‐positive. Microaerophilic. Ferments glucose. Most species are cultivable in complex, serum‐containing media that include N ‐acetylglucosamine. Optimum growth is between 33 and 38°C. Cells are polyploid, with each genome comprising a linear chromosome and one or more linear and circular plasmids. All known species are host‐associated organisms that are transmitted among mammalian, avian, and reptile reservoirs by a tick of the prostriate genus Ixodes . In unfed ticks, the organisms are located in the midgut and only travel to the salivary glands once the next blood meal commences. Transovarial transmission in tick vector does not occur. Members of this genus include all known agents of Lyme disease (Lyme borreliosis) as well as several species not associated with human disease. DNA G + C content (mol%) : 28–29. Type species : Borreliella burgdorferi (Adeolu and Gupta 2014, VL163) (basonym: Borrelia burgdorferi Johnson et al. 1984b VP ).

Three colony types of Lactobacillus were isolated from the stomach of LL colony stock Peromyscus leucopus deermice, a reservoir for several human zoonoses. Genome sequences revealed two isolates to be new strains of Lactobacillus animalis and Lactobacillus reuteri. The third was distinct from known species and was provisionally designated Lactobacillus sp. strain LL6.