RESUMO
The environmental risk of Lyme disease, defined by the density of Ixodes scapularis ticks and their prevalence of Borrelia burgdorferi infection, is increasing across the Ottawa, Ontario region, making this a unique location to explore the factors associated with environmental risk along a residential-woodland gradient. In this study, we collected I. scapularis ticks and trapped Peromyscus spp. mice, tested both for tick-borne pathogens, and monitored the intensity of foraging activity by deer in residential, woodland, and residential-woodland interface zones of four neighbourhoods. We constructed mixed-effect models to test for site-specific characteristics associated with densities of questing nymphal and adult ticks and the infection prevalence of nymphal and adult ticks. Compared to residential zones, we found a strong increasing gradient in tick density from interface to woodland zones, with 4 and 15 times as many nymphal ticks, respectively. Infection prevalence of nymphs and adults together was 15 to 24 times greater in non-residential zone habitats. Ecological site characteristics, including soil moisture, leaf litter depth, and understory density, were associated with variations in nymphal density and their infection prevalence. Our results suggest that high environmental risk bordering residential areas poses a concern for human-tick encounters, highlighting the need for targeted disease prevention.
Assuntos
Borrelia burgdorferi , Florestas , Ixodes , Doença de Lyme , Animais , Ixodes/microbiologia , Borrelia burgdorferi/isolamento & purificação , Borrelia burgdorferi/patogenicidade , Doença de Lyme/epidemiologia , Doença de Lyme/transmissão , Doença de Lyme/microbiologia , Prevalência , Ontário/epidemiologia , Peromyscus/microbiologia , Ninfa/microbiologia , Ecossistema , Humanos , Densidade Demográfica , Camundongos , Cervos/microbiologiaRESUMO
The development of interventions targeting reservoirs of Borrelia burgdorferi sensu stricto with acaricide to reduce the density of infected ticks faces numerous challenges imposed by ecological and operational limits. In this study, the pharmacokinetics, efficacy and toxicology of fluralaner were investigated in Mus musculus and Peromyscus leucopus mice, the main reservoir of B. burgdorferi in North America. Fluralaner showed rapid distribution and elimination, leading to fast plasma concentration (Cp) depletion in the first hours after administration followed by a slow elimination rate for several weeks, resulting in a long terminal half-life. Efficacy fell below 100% while Cp (± standard deviation) decreased from 196 ± 54 to 119 ± 62 ng/mL. These experimental results were then used in simulations of fluralaner treatment for a duration equivalent to the active period of Ixodes scapularis larvae and nymphs. Simulations showed that doses as low as 10 mg/kg have the potential to protect P. leucopus against infestation for a full I. scapularis active season if administered at least once every 7 days. This study shows that investigating the pharmacology of candidate acaricides in combination with pharmacokinetic simulations can provide important information to support the development of effective interventions targeting ecological reservoirs of Lyme disease. It therefore represents a critical step that may help surpass limits inherent to the development of these interventions.
Assuntos
Acaricidas , Borrelia burgdorferi , Reservatórios de Doenças , Ixodes , Doença de Lyme , Peromyscus , Animais , Doença de Lyme/tratamento farmacológico , Camundongos , Ixodes/microbiologia , Ixodes/efeitos dos fármacos , Reservatórios de Doenças/microbiologia , Peromyscus/microbiologia , Acaricidas/farmacocinética , Acaricidas/farmacologia , Borrelia burgdorferi/efeitos dos fármacos , Isoxazóis/farmacocinética , FemininoRESUMO
Borrelia burgdorferi, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed deermouse Peromyscus leucopus, is reported not to have reduced fitness following infection. Although laboratory strains of Mus musculus mice have successfully been leveraged to model acute human Lyme disease, the ability of these rodents to model B. burgdorferi-P. leucopus interactions remains understudied. Here, we compared infection of P. leucopus with B. burgdorferi B31 with infection of the traditional B. burgdorferi murine models-C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that B. burgdorferi was able to reach much higher burdens (10- to 30-times higher) in multiple M. musculus skin sites and that the overall dynamics of infection differed between the two rodent species. We also found that P. leucopus remained transmissive to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and rodent-to-tick transmission in these hosts. Similarly, we also observe evidence of inflammation in infected P. leucopus hearts. These observations provide new insight into reservoir species and the B. burgdorferi enzootic cycle.IMPORTANCEA Lyme disease-causing bacteria, Borrelia burgdorferi, must alternate between infecting a vertebrate host-usually rodents or birds-and ticks. In order to be successful in that endeavor, the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work, we examine how B. burgdorferi and one of its primary vertebrate reservoirs, Peromyscus leucopus, interact during an experimental infection. We find that B. burgdorferi appears to colonize its natural host less successfully than conventional laboratory mouse models, which aligns with a sustained seemingly anti-bacterial response by P. leucopus against the microbe. These data enhance our understanding of P. leucopus host-pathogen interactions and could potentially serve as a foundation to uncover ways to disrupt the spread of B. burgdorferi in nature.
Assuntos
Borrelia burgdorferi , Reservatórios de Doenças , Doença de Lyme , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Peromyscus , Animais , Peromyscus/microbiologia , Camundongos , Doença de Lyme/microbiologia , Doença de Lyme/transmissão , Doença de Lyme/veterinária , Borrelia burgdorferi/fisiologia , Borrelia burgdorferi/genética , Reservatórios de Doenças/microbiologia , Modelos Animais de Doenças , Ixodes/microbiologiaRESUMO
Lyme disease (LD), the most prevalent tick-borne disease of humans in the Northern Hemisphere, is caused by the spirochetal bacterium of Borreliella burgdorferi (Bb) sensu lato complex. In nature, Bb spirochetes are continuously transmitted between Ixodes ticks and mammalian or avian reservoir hosts. Peromyscus leucopus mice are considered the primary mammalian reservoir of Bb in the United States. Earlier studies demonstrated that experimentally infected P. leucopus mice do not develop disease. In contrast, C3H mice, a widely used laboratory strain of Mus musculus in the LD field, develop severe Lyme arthritis. To date, the exact tolerance mechanism of P. leucopus mice to Bb-induced infection remains unknown. To address this knowledge gap, the present study has compared spleen transcriptomes of P. leucopus and C3H/HeJ mice infected with Bb strain 297 with those of their respective uninfected controls. Overall, the data showed that the spleen transcriptome of Bb-infected P. leucopus mice was much more quiescent compared to that of the infected C3H mice. To date, the current investigation is one of the few that have examined the transcriptome response of natural reservoir hosts to Borreliella infection. Although the experimental design of this study significantly differed from those of two previous investigations, the collective results of the current and published studies have consistently demonstrated very limited transcriptomic responses of different reservoir hosts to the persistent infection of LD pathogens. Importance: The bacterium Borreliella burgdorferi (Bb) causes Lyme disease, which is one of the emerging and highly debilitating human diseases in countries of the Northern Hemisphere. In nature, Bb spirochetes are maintained between hard ticks of Ixodes spp. and mammals or birds. In the United States, the white-footed mouse, Peromyscus leucopus, is one of the main Bb reservoirs. In contrast to humans and laboratory mice (e.g., C3H mice), white-footed mice rarely develop clinical signs (disease) despite being (persistently) infected with Bb. How the white-footed mouse tolerates Bb infection is the question that the present study has attempted to address. Comparisons of genetic responses between Bb-infected and uninfected mice demonstrated that, during a long-term Bb infection, C3H mice reacted much stronger, whereas P. leucopus mice were relatively unresponsive.
Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Animais , Camundongos , Humanos , Peromyscus/microbiologia , Transcriptoma , Camundongos Endogâmicos C3H , Reservatórios de Doenças , Doença de Lyme/microbiologia , Borrelia burgdorferi/genética , Ixodes/microbiologia , Perfilação da Expressão GênicaRESUMO
The prevalence of antibiotic resistance genes (ARGs) can be driven by direct selection from antibiotic use and indirect selection from substances such as heavy metals (HMs). While significant progress has been made to characterize the influence of HMs on the enrichment and dissemination of ARGs in the environment, there is still much we do not know. To fill this knowledge gap, we present a comprehensive analysis of gut bacteria associated with wild cotton mice (Peromyscus gossypinus) trapped from several areas affected by legacies of HM and radionuclide contamination. We explore how these contaminants affect gut microbial community (GMC) composition and diversity and the enrichment of antibiotic, biocide, and metal resistance genes. Although we were able to identify that a myriad of co-occurring antimicrobial and HM resistance genes appear in mice from all areas, including those without a history of contamination, the proportions of co-occurring ARGs and metal resistance genes (MRGs) are higher in sites with radionuclide contamination. These results support those from several previous studies and enhance our understanding of the coselection process, while providing new insights into the ubiquity of antimicrobial resistance in the resistome of wild animals. IMPORTANCE Antimicrobial resistance is a serious global public health concern because of its prevalence and ubiquitous distribution. The rapid dissemination of antibiotic resistance genes is thought to be the result of the massive overuse of antibiotics in agriculture and therapeutics. However, previous studies have demonstrated that the spread of antibiotic resistance genes can also be influenced by heavy metal contamination. This coselection phenomenon, whereby different resistance determinants are genetically linked on the same genetic element (coresistance) or a single genetic element provides resistance to multiple antimicrobial agents (cross-resistance), has profound clinical and environmental implications. In contrast to antibiotics, heavy metals can persist in the environment as a selection pressure for long periods of time. Thus, it is important to understand how antibiotic resistance genes are distributed in the environment and to what extent heavy metal contaminants may be driving their selection, which we have done in one environmental setting.
Assuntos
Bactérias/efeitos dos fármacos , Bactérias/genética , Microbioma Gastrointestinal , Metais Pesados/farmacologia , Peromyscus/microbiologia , Radioisótopos/farmacologia , Animais , Animais Selvagens/metabolismo , Animais Selvagens/microbiologia , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Desinfetantes/farmacologia , Farmacorresistência Bacteriana , Ecossistema , Feminino , Masculino , Metais Pesados/análise , Camundongos , Radioisótopos/análise , Sudeste dos Estados UnidosRESUMO
Animals that are competent reservoirs of zoonotic pathogens commonly suffer little morbidity from the infections. To investigate mechanisms of this tolerance of infection, we used single-dose lipopolysaccharide (LPS) as an experimental model of inflammation and compared the responses of two rodents: Peromyscus leucopus, the white-footed deermouse and reservoir for the agents of Lyme disease and other zoonoses, and the house mouse Mus musculus Four hours after injection with LPS or saline, blood, spleen, and liver samples were collected and subjected to transcriptome sequencing (RNA-seq), metabolomics, and specific reverse transcriptase quantitative PCR (RT-qPCR). Differential expression analysis was at the gene, pathway, and network levels. LPS-treated deermice showed signs of sickness similar to those of exposed mice and had similar increases in corticosterone levels and expression of interleukin 6 (IL-6), tumor necrosis factor, IL-1ß, and C-reactive protein. By network analysis, the M. musculus response to LPS was characterized as cytokine associated, while the P. leucopus response was dominated by neutrophil activity terms. In addition, dichotomies in the expression levels of arginase 1 and nitric oxide synthase 2 and of IL-10 and IL-12 were consistent with type M1 macrophage responses in mice and type M2 responses in deermice. Analysis of metabolites in plasma and RNA in organs revealed species differences in tryptophan metabolism. Two genes in particular signified the different phenotypes of deermice and mice: the Slpi and Ibsp genes. Key RNA-seq findings for P. leucopus were replicated in older animals, in a systemic bacterial infection, and with cultivated fibroblasts. The findings indicate that P. leucopus possesses several adaptive traits to moderate inflammation in its balancing of infection resistance and tolerance.IMPORTANCE 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 deermouse, 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. Mechanisms of this phenomenon of infection tolerance and entailed trade-off costs are poorly understood. Using a single injection of lipopolysaccharide (LPS) endotoxin as a proxy for infection, we found that deermice differed from the mouse (Mus musculus) in responses to LPS in several diverse pathways, including innate immunity, oxidative stress, and metabolism. Features distinguishing the deermice cumulatively would moderate downstream ill effects of LPS. Insights gained from the P. leucopus model in the laboratory have implications for studying infection tolerance in other important reservoir species, including bats and other types of wildlife.
Assuntos
Reservatórios de Doenças/microbiologia , Endotoxinas/administração & dosagem , Inflamação/genética , Peromyscus/microbiologia , Zoonoses/imunologia , Zoonoses/microbiologia , Animais , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/imunologia , Endotoxinas/imunologia , Feminino , Perfilação da Expressão Gênica , Inflamação/imunologia , Doença de Lyme/microbiologia , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Peromyscus/imunologia , Análise de Sequência de RNARESUMO
The variable response of wild mice to Yersinia pestis infection, the causative agent of plague, has generated much speculation concerning their role in the ecology of this potentially lethal disease. Researchers have questioned the means by which Y. pestis is maintained in nature and also sought methods for managing the disease. Here we assessed the efficacy of a new tool, the sylvatic plague vaccine (SPV), in wild-caught northern grasshopper mice (Onychomys leucogaster) and commercially acquired Sonoran deer mice (Peromyscus maniculatus sonoriensis). More than 40% of the animals survived a subcutaneous Y. pestis challenge of 175,000 colony forming units (over 30,000 times the white mouse 50% lethal dose) in both vaccine-treated and control groups. Our results indicate that SPV distribution is unlikely to protect adult mice from plague infection in field settings and corroborate the heterogeneous response to Y. pestis infection in mice reported by others.
Assuntos
Camundongos/microbiologia , Peromyscus/microbiologia , Vacina contra a Peste , Peste/veterinária , Doenças dos Roedores , Yersinia pestis , Animais , Peste/prevenção & controle , Doenças dos Roedores/microbiologia , Doenças dos Roedores/prevenção & controleRESUMO
Deer tick-transmitted Borrelia burgdorferisensu stricto (Lyme disease) and Babesia microti (babesiosis) increasingly burden public health across eastern North America. The white-footed mouse is considered the primary host for subadult deer ticks and the most important reservoir host for these and other disease agents. Local transmission is thought to be modulated by less reservoir-competent hosts, such as deer, diverting ticks from feeding on mice. We measured the proportion of mouse-fed or deer-fed host-seeking nymphs from 4 sites during 2 transmission seasons by blood meal remnant analysis using a new retrotransposon-based quantitative PCR (qPCR) assay. We then determined the host that was associated with the infection status of the tick. During the first year, the proportion of mouse-fed ticks ranged from 17% on mainland sites to 100% on an island, while deer-fed ticks ranged from 4% to 24%. The proportion of ticks feeding on mice and deer was greater from island sites than mainland sites (on average, 92% versus 43%). Mouse-fed ticks decreased significantly during year 2 in 3 of 4 sites (most were <20%), while deer-fed ticks increased for all sites (75% at one site). Overall, ticks were more likely to be infected when they had fed on mice (odds ratio [OR] of 2.4 and 1.6 for Borrelia and Babesia, respectively) and were less likely to be infected if they had fed on deer (OR, 0.8 and 0.4). We conclude that host utilization by deer ticks is characterized by significant spatiotemporal diversity, which may confound efficacy tests of interventions targeting reservoir hosts.IMPORTANCE White-footed mice are thought to be the most important reservoir host for the deer tick-transmitted pathogens that cause Lyme disease and human babesiosis because they are the primary host for immature ticks. Transmission would be reduced, however, if ticks feed on deer, which are not capable of infecting ticks with either pathogen. By directly measuring whether ticks had fed on either mice or deer using a new quantitative PCR (qPCR) assay to detect remnants of host DNA leftover from the larval blood meal, we demonstrate that host utilization by ticks varies significantly over time and space and that mice often feed fewer ticks than expected. This finding has implications for our understanding of the ecology of these diseases and for the efficacy of control measures.
Assuntos
Babesia microti/isolamento & purificação , Borrelia burgdorferi/isolamento & purificação , Cervos , Ixodes/microbiologia , Peromyscus , Animais , DNA/análise , Cervos/sangue , Cervos/genética , Cervos/microbiologia , Feminino , New England , Ninfa/microbiologia , Peromyscus/sangue , Peromyscus/genética , Peromyscus/microbiologia , RetroelementosRESUMO
The blacklegged tick (Ixodes scapularis Say) is the primary vector of Borrelia burgdorferi sensu stricto (Spirochaetales: Spirochaetaceae), the Lyme disease agent in North America. The basic reproduction number (R0) for B. burgdorferi in I. scapularis in the Northeast is highly sensitive to the probability that engorged larvae survive the winter, molt into nymphs, and find a host. These processes are dependent on local environmental variables, including climate, host population size and movement, and tick behavior. A simple model is presented for estimating host-finding success from the ratio of tick abundance in two subsequent years, accounting for overwinter survival and possible differences in host associations between nymphs and larvae. This model was parameterized using data from two sites in mainland Connecticut and two on Block Island, RI. Host abundance and tick burdens were estimated via mark-recapture trapping of the primary host, Peromyscus leucopus Rafinesque. Overwintering survival was estimated using engorged larvae placed in field enclosures at each site. Only nymphs were recovered alive, and no significant differences in model parameters were observed between Connecticut and Block Island. Host-finding success was predicted to be high across a wide range of host association patterns at three of four sites. Assuming equivalent host association between larvae and nymphs, R0 was also estimated to be greater than one at three of four sites, suggesting these conditions allow for the persistence of B. burgdorferi. The model output was highly sensitive to differences between nymphal and larval host associations.
Assuntos
Ixodes , Doença de Lyme , Modelos Estatísticos , Infestações por Carrapato , Animais , Borrelia burgdorferi , Clima , Reservatórios de Doenças , Comportamento Alimentar , Interações Hospedeiro-Parasita/fisiologia , Ixodes/microbiologia , Ixodes/fisiologia , Doença de Lyme/transmissão , Ninfa/microbiologia , Ninfa/fisiologia , Peromyscus/microbiologia , Peromyscus/parasitologia , Densidade Demográfica , Doenças dos Roedores , Estações do Ano , Infestações por Carrapato/transmissão , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Microbioma Gastrointestinal/genética , Peromyscus/microbiologia , Zoonoses/microbiologia , Animais , Humanos , Lactobacillus/genética , Lactobacillus/metabolismo , Doença de Lyme/epidemiologia , Doença de Lyme/etiologia , América do Norte , Peromyscus/genética , Zoonoses/genéticaRESUMO
Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.
Assuntos
Compostos Benzidrílicos/toxicidade , Encéfalo/efeitos dos fármacos , Disbiose/induzido quimicamente , Disruptores Endócrinos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Genisteína/toxicidade , Peromyscus/microbiologia , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Transtorno do Espectro Autista/induzido quimicamente , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Dieta , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Lactação , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Metaboloma/efeitos dos fármacos , Peromyscus/embriologia , Peromyscus/crescimento & desenvolvimento , Peromyscus/metabolismo , Lesões Pré-Concepcionais/induzido quimicamente , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/microbiologia , Comportamento Social , Especificidade da Espécie , Vocalização AnimalRESUMO
Blacklegged ticks (Ixodes scapularis) are the principal vector for Borrelia burgdorferi, among other infectious agents, in the northeastern, mid-Atlantic, and upper midwestern USA. White-footed mice (Peromyscus leucopus) are the primary and most competent reservoir host of B. burgdorferi in the Northeast. Live reservoir-targeted vaccines (RTVs) to limit enzootic transmission of B. burgdorferi were previously developed and successfully evaluated in laboratory and controlled field trials. A novel, inactivated RTV was developed to minimize regulatory and market challenges facing previous RTVs based on live bacterial or viral vehicles. Thirty-two residential properties in Redding, Connecticut, participated in a field trial of an orally delivered, inactivated RTV efficacy study (2015-2016). During the two-year vaccination period, a significant decrease in the percentage of B. burgdorferi-infected I. scapularis larvae parasitizing P. leucopus was observed, as was a significant reduction in the percentage of infected P. leucopus on RTV-treated properties when compared to control properties. This novel inactivated RTV was effective in reducing numbers of B. burgdorferi-infected I. scapularis and B. burgdorferi-infected P. leucopus on properties where it was distributed.
Assuntos
Vacinas Bacterianas/administração & dosagem , Borrelia burgdorferi , Ixodes/microbiologia , Doença de Lyme/veterinária , Peromyscus/microbiologia , Animais , Antígenos de Bactérias/imunologia , Connecticut , Larva , Doença de Lyme/prevenção & controleRESUMO
Peromyscus leucopus (the white-footed mouse) is a known reservoir of the Lyme disease spirochete Borrelia burgdorferi. Sampling of white-footed mice allows for year-round B. burgdorferi surveillance as well as opportunities to establish the diversity of the different variants in a geographic region. This study explores the prevalence of B. burgdorferi infections in the tissues of white-footed mice, investigates the correlations between B. burgdorferi infected tissues, and determines the optimum field methods for surveillance of B. burgdorferi in P. leucopus. A total of 90 mice and 573 tissues (spleen, liver, ear, tongue, tail, heart, and kidney) were screened via nested PCR for B. burgdorferi infections. A large number of infections were found in the 90 mice as well as multiple infections within individual mice. Infections in a single mouse tissue (spleen, liver, ear, tongue and tail) were predictive of concurrent infection in other tissues of the same mouse at a statistically significant level. Ear tissue accounted for 68.4% of detected infections, which increased to 78.9% of the infected mice with the inclusion of tail samples. The use of ear punch or tail snip samples (used individually or in tandem) have multiple advantages over current Lyme disease ecological studies and surveillance methodologies, including lower associated costs, minimization of delays, year-round B. burgdorferi testing opportunities, as well as longitudinal monitoring of B. burgdorferi in defined geographic regions. In the absence of an effective vaccine, personal prevention measures are currently the most effective way to reduce Lyme disease transmission to humans. Thus, the identification and monitoring of environmental reservoirs to inform at-risk populations remains a priority. The sampling methods proposed in this study provide a reasonable estimate of B. burgdorferi in white-footed mice in a timely and cost-effective manner.
Assuntos
Borrelia burgdorferi/isolamento & purificação , Doença de Lyme/veterinária , Peromyscus/microbiologia , Doenças dos Roedores/microbiologia , Manejo de Espécimes/normas , Animais , Reservatórios de Doenças , Feminino , Doença de Lyme/microbiologia , Masculino , Camundongos , Doenças dos Roedores/epidemiologia , Manejo de Espécimes/métodosRESUMO
Complement is a key first line innate host defense system in the blood of vertebrates. Upon activation, this powerful defense mechanism can elicit inflammatory responses, lyse non-self-cells, or mark them for opsonophagocytic removal. Blood-feeding arthropods thus require the ability to block host complement activation in the bloodmeal to prevent undesired cell or tissue damage during feeding. The soft tick Ornithodoros moubata produces a complement inhibitory protein, OmCI. This protein binds to a mammalian complement protein C5 and blocks further activation of complement cascades, which results in the prevention of complement-mediated bacterial killing through membrane attack complex. Interestingly, the amino acids involved in OmCI binding are highly conserved among mammalian and avian C5, but the ability of this protein to inhibit the complement from birds remains unclear. Here we demonstrated that OmCI is capable of preventing quail complement-mediated erythrocyte lysis, inhibiting the capability of this animal's complement to eliminate a serum-sensitive Lyme disease bacterial strain. We also found that the ability of OmCI to inhibit quail complement-mediated killing of Lyme disease bacteria can be extended to different domestic and wild birds. Our results illustrate the utility of OmCI to block bird complement. These results provide the foundation for further use of this protein as a tool to study the molecular basis of avian complement and pathogen evasion to such a defense mechanism.
Assuntos
Proteínas de Artrópodes/metabolismo , Complemento C5/genética , Coturnix/genética , Ornithodoros/genética , Peromyscus/genética , Ligação Proteica , Proteínas e Peptídeos Salivares/metabolismo , Sequência de Aminoácidos , Animais , Ativação do Complemento , Complemento C5/química , Complemento C5/metabolismo , Coturnix/microbiologia , Ornithodoros/metabolismo , Peromyscus/microbiologia , Alinhamento de SequênciaRESUMO
The white-footed mouse, Peromyscus leucopus (Rafinesque), is a reservoir for the Lyme disease spirochete Borrelia burgdorferi sensu stricto in the eastern half of the United States, where the blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae), is the primary vector. In the Midwest, an additional Lyme disease spirochete, Borrelia mayonii, was recorded from naturally infected I. scapularis and P. leucopus. However, an experimental demonstration of reservoir competence was lacking for a natural tick host. We therefore experimentally infected P. leucopus with B. mayonii via I. scapularis nymphal bites and then fed uninfected larvae on the mice to demonstrate spirochete acquisition and passage to resulting nymphs. Of 23 mice fed on by B. mayonii-infected nymphs, 21 (91%) developed active infections. The infection prevalence for nymphs fed as larvae on these infected mice 4 wk post-infection ranged from 56 to 98%, and the overall infection prevalence for 842 nymphs across all 21 P. leucopus was 75% (95% confidence interval, 72-77%). To assess duration of infectivity, 10 of the P. leucopus were reinfested with uninfected larval ticks 12 wk after the mice were infected. The overall infection prevalence for 480 nymphs across all 10 P. leucopus at the 12-wk time point was 26% (95% confidence interval, 23-31%), when compared with 76% (95% confidence interval, 71-79%) for 474 nymphs from the same subset of 10 mice at the 4-wk time point. We conclude that P. leucopus is susceptible to infection with B. mayonii via bite by I. scapularis nymphs and an efficient reservoir for this Lyme disease spirochete.
Assuntos
Vetores Aracnídeos/microbiologia , Reservatórios de Doenças , Ixodes/microbiologia , Doença de Lyme/transmissão , Peromyscus/microbiologia , Spirochaetales/fisiologia , Animais , Vetores Aracnídeos/crescimento & desenvolvimento , Infecções por Borrelia/transmissão , Ixodes/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Larva/microbiologia , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , Peromyscus/parasitologiaRESUMO
'Candidatus Ehrlichia khabarensis' was first described from rodents and insectivores in the Far East territory of Khabarovsk on the Russian Pacific Coast. Here we report the detection of DNA from this microorganism in rodents and fed ticks collected from rodents in British Columbia, Canada in 2013-2014. 'Candidatus Ehrlichia khabarensis' was detected in (i) a female Ixodes angustus tick collected from a Peromyscus maniculatus; (ii) a female Dermacentor andersoni tick collected from a Perognathus parvus; (iii) a pool of 2 larval Ixodes pacificus ticks collected from a single P. maniculatus; and (iv) a pool of 3 nymphal I. pacificus ticks collected from a single P. maniculatus. Three of these four rodents (2 P. maniculatus and 1 P. parvus) with infected ticks also had evidence of 'Candidatus Ehrlichia khabarensis' in at least one tissue type. The infected P. maniculatus and Ixodes ticks came from the Vancouver area in western British Columbia and the P. parvus and Dermacentor tick from an inland site in central British Columbia. Although it remains to be determined whether 'Candidatus Ehrlichia khabarensis' has any negative impacts on wildlife, domestic animals or humans, we note that all three tick species found to contain the DNA of this microorganism are known to bite humans. Future detection of this microorganism either in ticks collected from rodents and allowed to molt to the next life stage prior to being tested, or from host-seeking ticks, is required to determine if it can survive the tick's molt after being ingested via an infectious blood meal.
Assuntos
Dermacentor/microbiologia , Ehrlichia/isolamento & purificação , Ixodes/microbiologia , Roedores/microbiologia , Animais , Colúmbia Britânica , Dermacentor/crescimento & desenvolvimento , Feminino , Ixodes/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Larva/microbiologia , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , Peromyscus/microbiologia , Peromyscus/parasitologia , Roedores/parasitologiaRESUMO
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.
Assuntos
DNA Mitocondrial/genética , Reservatórios de Doenças , Genoma , Peromyscus/genética , Animais , Animais de Laboratório/genética , Animais Selvagens/genética , Vetores Aracnídeos/microbiologia , Borrelia , Infecções por Borrelia/genética , Infecções por Borrelia/microbiologia , Borrelia burgdorferi/isolamento & purificação , Feminino , Perfilação da Expressão Gênica , Haplótipos , Ixodes/microbiologia , Doença de Lyme/microbiologia , Doença de Lyme/transmissão , Doença de Lyme/veterinária , Muridae/classificação , Muridae/genética , Especificidade de Órgãos , Peromyscus/classificação , Peromyscus/microbiologia , Filogenia , Pseudogenes , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/microbiologia , Doenças dos Roedores/parasitologia , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Picadas de Carrapatos/microbiologia , Picadas de Carrapatos/veterinária , Estados UnidosRESUMO
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.
Assuntos
Doença de Lyme/genética , Peromyscus/genética , Spirochaetales/genética , Doenças Transmitidas por Carrapatos/genética , Animais , Genoma/genética , Humanos , Anotação de Sequência Molecular , Peromyscus/microbiologia , Análise de Sequência de RNA , Doenças Transmitidas por Carrapatos/microbiologia , Sequenciamento Completo do GenomaRESUMO
Plague is a lethal zoonotic disease associated with rodents worldwide. In the western United States, plague outbreaks can decimate prairie dog (Cynomys spp.) colonies. However, it is unclear where the causative agent, Yersinia pestis, of this flea-borne disease is maintained between outbreaks, and what triggers plague-induced prairie dog die-offs. Less susceptible rodent hosts, such as mice, could serve to maintain the bacterium, transport infectious fleas across a colony, or introduce the pathogen to other colonies, possibly facilitating an outbreak. Here, we assess the potential role of two short-lived rodent species, North American deer mice (Peromyscus maniculatus) and Northern grasshopper mice (Onychomys leucogaster) in plague dynamics on prairie dog colonies. We live-trapped short-lived rodents and collected their fleas on black-tailed (Cynomys ludovicianus, Montana and South Dakota), white-tailed (Cynomys leucurus, Utah and Wyoming), and Utah prairie dog colonies (Cynomys parvidens, Utah) annually, from 2013 to 2016. Plague outbreaks occurred on colonies of all three species. In all study areas, deer mouse abundance was high the year before plague-induced prairie dog die-offs, but mouse abundance per colony was not predictive of plague die-offs in prairie dogs. We did not detect Y. pestis DNA in mouse fleas during prairie dog die-offs, but in three cases we found it beforehand. On one white-tailed prairie dog colony, we detected Y. pestis positive fleas on one grasshopper mouse and several prairie dogs live-trapped 10 days later, months before visible declines and plague-confirmed mortality of prairie dogs. On one black-tailed prairie dog colony, we detected Y. pestis positive fleas on two deer mice 3 months before evidence of plague was detected in prairie dogs or their fleas and also well before a plague-induced die-off. These observations of plague positive fleas on mice could represent early spillover events of Y. pestis from prairie dogs or an unknown reservoir, or possible movement of infectious fleas by mice.
Assuntos
Peste/veterinária , Sciuridae/microbiologia , Sifonápteros/microbiologia , Yersinia pestis/isolamento & purificação , Animais , Arvicolinae/microbiologia , Arvicolinae/parasitologia , DNA Bacteriano , Surtos de Doenças , Infestações por Pulgas , Insetos Vetores/microbiologia , Peromyscus/microbiologia , Peromyscus/parasitologia , Peste/epidemiologia , Peste/mortalidade , Sciuridae/parasitologia , Estados UnidosRESUMO
Vertebrate gastrointestinal tracts have co-existed with microbes over millennia. These microbial communities provide their host with numerous benefits. However, the extent to which different environmental factors contribute to the assemblage of gut microbial communities is not fully understood. The purpose of this study was to determine how the external environment influences the development of gut microbiome communities (GMCs). Faecal samples were collected from deer mice (Peromyscus maniculatus) born and raised in captivity and the wild at approximately 3-5 weeks of age. Additional samples were collected 2 weeks later, with a subset of individuals being translocated between captive and wild environments. Microbial data were analysed using 16S rRNA next-generation Illumina HiSeq sequencing methods. GMCs of deer mice were more similar between neighbours who shared the same environment, regardless of where an individual was born, demonstrating that GMCs are significantly influenced by the surrounding environment and can rapidly change over time. Mice in natural environments contained more diverse GMCs with higher relative abundances of Ruminoccocaceae, Helicobacteraceae and Lachnospiraceae spp. Future studies should examine the fitness consequences associated with the presence/absence of microbes that are characteristic of GMCs of wild populations to gain a better understanding of environment-microbe-host evolutionary and ecological relationships.