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The genome of Peromyscus leucopus, natural host for Lyme disease and other emerging infections.

ABSTRACT: 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.

SUBMITTER: Long AD

PROVIDER: S-EPMC6656541 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The genome of Peromyscus leucopus, natural host for Lyme disease and other emerging infections.

Long Anthony D AD Baldwin-Brown James J Tao Yuan Y Cook Vanessa J VJ Balderrama-Gutierrez Gabriela G Corbett-Detig Russell R Mortazavi Ali A Barbour Alan G AG

Science advances 20190724 7

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 ag ...[more]

PMID: 31355335

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Project description:UnlabelledThe rodent Peromyscus leucopus is a major natural reservoir for the Lyme disease agent Borrelia burgdorferi and a host for its vector Ixodes scapularis. At various locations in northeastern United States 10 to 15 B. burgdorferi strains coexist at different prevalences in tick populations. We asked whether representative strains of high or low prevalence differed in their infections of P. leucopus. After 5 weeks of experimental infection of groups with each of 6 isolates, distributions and burdens of bacteria in tissues were measured by quantitative PCR, and antibodies to B. burgdorferi were evaluated by immunoblotting and protein microarray. All groups of animals were infected in their joints, ears, tails, and hearts, but overall spirochete burdens were lower in animals infected with low-prevalence strains. Animals were similar regardless of the infecting isolate in their levels of antibodies to whole cells, FlaB, BmpA, and DbpB proteins, and the conserved N-terminal region of the serotype-defining OspC proteins. But there were strain-specific antibody responses to full-length OspC and to plasmid-encoded VlsE, BBK07, and BBK12 proteins. Sequencing of additional VlsE genes revealed substantial diversity within some pairs of strains but near-identical sequences within other pairs, which otherwise differed in their ospC alleles. The presence or absence of full-length bbk07 and bbk12 genes accounted for the differences in antibody responses. We propose that for B. burgdorferi, there is selection in reservoir species for (i) sequence diversity, as for OspC and VlsE, and (ii) the presence or absence of polymorphisms, as for BBK07 and BBK12.ImportanceHumans are dead-end hosts for Borrelia agents of Lyme disease (LD), and, thus, irrelevant for the pathogens' maintenance. Many reports of human cases and laboratory mouse infections exist, but less is known about infection and immunity in natural reservoirs, such as the rodent Peromyscus leucopus. We observed that high- and low-prevalence strains of Borrelia burgdorferi were capable of infecting P. leucopus but elicited different patterns of antibody responses. Antibody reactivities to the VlsE protein were as type-specific as previously characterized reactivities to serotype-defining OspC proteins. In addition, the low-prevalence strains lacked full-length genes for two proteins that (i) are encoded by a virulence-associated plasmid in some high-prevalence strains and (ii) LD patients and field-captured rodents commonly have antibodies to. Immune selection against these genes may have led to null phenotype lineages that can infect otherwise immune hosts but at the cost of reduced fitness and lower prevalence.

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The genome of Peromyscus leucopus, natural host for Lyme disease and other emerging infections.

Publications

The genome of <i>Peromyscus leucopus</i>, natural host for Lyme disease and other emerging infections.

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