Host phylogeny, geographic overlap, and roost sharing shape parasite communities in European bats

How multitrophic relationships between wildlife communities and their ectoparasitic vectors interact to shape the diversity of vector-borne microorganisms is poorly understood. Nested levels of dependence among microbes, vectors, and vertebrate hosts may have complicated effects on both microbial community assembly and evolution. We examined Bartonella sequences from European bats and their ectoparasites with a combination of network analysis, Bayesian phylogenetics, tip-association and cophylogeny tests, and linear regression to understand the ecological and evolutionary processes that shape parasite communities. We detected seven batectoparasite-Bartonella communities that can be differentiated based on bat families and roosting patterns. Tips of the Bartonella tree were significantly clustered by host taxonomy and geography. We also found significant evidence of evolutionary congruence between bat host and Bartonella phylogenies, indicating that bacterial species have evolved to infect related bat species. Exploring these ecological and evolutionary associations further, we found that sharing of Bartonella species among bat hosts was strongly associated with host phylogenetic distance and roost sharing and less strongly with geographic range overlap. Ectoparasite sharing between hosts was strongly predicted by host phylogenetic distance, roost sharing, and geographic overlap but had no additive effect on Bartonella sharing. Finally, historical Bartonella host-switching was more frequent for closely related bats after accounting for sampling bias among bat species. This study helps to disentangle the complex ecology and evolution of Bartonella bacteria in bat species and their arthropod vectors. Our work provides insight into the important mechanisms that partition parasite communities among hosts, particularly the effect of host phylogeny and roost sharing, and could help to elucidate the evolutionary patterns of other diverse vector-borne microorganisms

Fine-scale Identification of the Most Likely Source of a Human Plague Infection

We describe an analytic approach to provide fine-scale discrimination among multiple infection source hypotheses. This approach uses mutation-rate data for rapidly evolving multiple locus variable-number tandem repeat loci in probabilistic models to identify the most likely source. We illustrate the utility of this approach using data from a North American human plague investigation

Genomic changes associated with the evolutionary transition of an insect gut symbiont into a blood-borne pathogen.

The genus Bartonella comprises facultative intracellular bacteria with a unique lifestyle. After transmission by blood-sucking arthropods they colonize the erythrocytes of mammalian hosts causing acute and chronic infectious diseases. Although the pathogen-host interaction is well understood, little is known about the evolutionary origin of the infection strategy manifested by Bartonella species. Here we analyzed six genomes of Bartonella apis, a honey bee gut symbiont that to date represents the closest relative of pathogenic Bartonella species. Comparative genomics revealed that B. apis encodes a large set of vertically inherited genes for amino acid and cofactor biosynthesis and nitrogen metabolism. Most pathogenic bartonellae have lost these ancestral functions, but acquired specific virulence factors and expanded a vertically inherited gene family for harvesting cofactors from the blood. However, the deeply rooted pathogen Bartonella tamiae has retained many of the ancestral genome characteristics reflecting an evolutionary intermediate state toward a host-restricted intraerythrocytic lifestyle. Our findings suggest that the ancestor of the pathogen Bartonella was a gut symbiont of insects and that the adaptation to blood-feeding insects facilitated colonization of the mammalian bloodstream. This study highlights the importance of comparative genomics among pathogens and non-pathogenic relatives to understand disease emergence within an evolutionary-ecological framework

First Reported Prairie Dog–to-Human Tularemia Transmission, Texas, 2002

A tularemia outbreak, caused by Francisella tularensis type B, occurred among wild-caught, commercially traded prairie dogs. F. tularensis microagglutination titers in one exposed person indicated recent infection. These findings represent the first evidence for prairie-dog-to-human tularemia transmission and demonstrate potential human health risks of the exotic pet trade

Host Phylogeny, Geographic Overlap, and Roost Sharing Shape Parasite Communities in European Bats

How multitrophic relationships between wildlife communities and their ectoparasitic vectors interact to shape the diversity of vector-borne microorganisms is poorly understood. Nested levels of dependence among microbes, vectors, and vertebrate hosts may have complicated effects on both microbial community assembly and evolution. We examined Bartonella sequences from European bats and their ectoparasites with a combination of network analysis, Bayesian phylogenetics, tip-association and cophylogeny tests, and linear regression to understand the ecological and evolutionary processes that shape parasite communities. We detected seven bat–ectoparasite–Bartonella communities that can be differentiated based on bat families and roosting patterns. Tips of the Bartonella tree were significantly clustered by host taxonomy and geography. We also found significant evidence of evolutionary congruence between bat host and Bartonella phylogenies, indicating that bacterial species have evolved to infect related bat species. Exploring these ecological and evolutionary associations further, we found that sharing of Bartonella species among bat hosts was strongly associated with host phylogenetic distance and roost sharing and less strongly with geographic range overlap. Ectoparasite sharing between hosts was strongly predicted by host phylogenetic distance, roost sharing, and geographic overlap but had no additive effect on Bartonella sharing. Finally, historical Bartonella host-switching was more frequent for closely related bats after accounting for sampling bias among bat species. This study helps to disentangle the complex ecology and evolution of Bartonella bacteria in bat species and their arthropod vectors. Our work provides insight into the important mechanisms that partition parasite communities among hosts, particularly the effect of host phylogeny and roost sharing, and could help to elucidate the evolutionary patterns of other diverse vector-borne microorganisms

A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation

Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals—5 of which were identified only with the custom arrays—and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10−29); for ESR, at the HBB (rs4910472, p = 2.31×10−11) and UCN119B/SPPL3 (rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and in CADM3 (rs3026968, p = 7.63×10−13); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10−21), near DARC (rs3845624, p = 1.43×10−10), UNC119B/SPPL3 (rs11829037, p = 1.50×10−14), and ICOSLG/AIRE (rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process

Population- and individual-specific regulatory variation in Sardinia

Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.M.P. is supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 633964 (ImmunoAgeing). Z.Z. is supported by the National Science Foundation (NSF) GRFP (DGE- 114747) and by the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). Z.Z., J.R.D., and G.T.H. also acknowledge support from the Stanford Genome Training Program (SGTP; NIH/NHGRI T32HG000044). J.R.D. is supported by the Stanford Graduate Fellowship. K.R.K. is supported by Department of Defense, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEQ) Fellowship 32 CFR 168a. S.J.S. is supported by the NIHR Cambridge Biomedical Research Centre. The SardiNIA project is supported in part by the intramural program of the National Institute on Aging through contract HHSN271201100005C to the Consiglio Nazionale delle Ricerche of Italy. The RNA sequencing was supported by the PB05 InterOmics MIUR Flagship grant; by the FaReBio2011 “Farmaci e Reti Biotecnologiche di Qualità” grant; and by Sardinian Autonomous Region (L.R. no. 7/2009) grant cRP3-154 to F. Cucca, who is also supported by the Italian Foundation for Multiple Sclerosis (FISM 2015/R/09) and by the Fondazione di Sardegna (ex Fondazione Banco di Sardegna, Prot. U1301.2015/AI.1157.BE Prat. 2015-1651). S.B.M. is supported by the US National Institutes of Health through R01HG008150, R01MH101814, U01HG007436, and U01HG009080. All of the authors would like to thank the CRS4 and the SCGPM for the computational infrastructure supporting this project

Prevalence of Antibody to Hepatitis E Virus among Rodents in the United States

The recent identification of antibody to hepatitis E virus (HEV) in pigs, sheep, and cattle and characterization of an HEV isolated from domestic pigs suggest animal reservoirs for this virus. To investigate whether rodents might be a natural reservoir of HEV, the prevalence of anti-HEV was determined among a variety of species throughout the United States. Serum samples were obtained from 806 rodents of 26 species in 15 genera. Anti-HEV prevalence was assessed by 2 EIAs (mosaic protein- and 55-kDa protein-based), which gave concordant results. The highest prevalence of antibody was found in the genus Rattus (59.7%; 66/278). Overall, rodents from urban habitats had a significantly higher prevalence of anti-HEV than did animals captured from rural areas. A high prevalence of anti-HEV was found in animals captured on mainland versus barrier islands. The results from this study provide convincing evidence of widespread HEV or HEV-like infection in rodents of the United States

Persistent Infection or Successive Reinfection of Deer Mice with \u3ci\u3eBartonella vinsonii subsp. arupensis\u3c/i\u3e

Bartonella infections are common in rodents. From 1994 to 2006, longitudinal studies of a rodent community, consisting mainly of deer mice (Peromyscus maniculatus), were conducted in southwestern Colorado to study hantaviruses. Blood samples from deer mice captured one or more times during the period 2003 to 2006 (n = 737) were selected to study bartonellae in deer mice. Bartonellae were found to be widely distributed in that population, with an overall prevalence of 82.4% (607/737 mice). No correlation was found between bartonella prevalence and deer mouse weight or sex. Persistent or successive infections with bartonellae were observed in deer mice captured repeatedly, with a prevalence of 83.9% (297/354), and the infection appeared to last for more than 1 year in some of them. Persistent infection with bartonellae may explain the high prevalence of these bacteria in deer mice at this site and, perhaps, elsewhere. Genetic analysis demonstrated that deer mouse-borne bartonella isolates at this site belong to the same species, B. vinsonii subsp. arupensis, demonstrating a specific relationship between B. vinsonii subsp. arupensis and deer mice