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1. Host adaptation drives genetic diversity in a vector-borne disease system

   https://doi.org/10.1101/2022.05.19.492734  

   Combs, MA; Tufts, DM; Adams, B; Lin, YP; Kolokotronis, SO; Diuk-Wasser, MA (May 2022, bioRxiv)

   The range of hosts a pathogen can infect is a key trait influencing human disease risk and reservoir host infection dynamics. Borrelia burgdorferi sensu stricto (Bb), an emerging zoonotic pathogen, causes Lyme disease and is widely considered a host generalist, commonly infecting mammals and birds. Yet the extent of intraspecific variation in Bb host breadth, its role in determining host competence and potential implications to human infection remain unclear. We conducted a long-term study of Bb diversity, defined by the polymorphic ospC locus, across white-footed mice, passerine birds, and tick vectors leveraging long-read amplicon sequencing. Our results reveal strong variation in host breadth across Bb genotypes, exposing a spectrum of genotype-specific host-adapted phenotypes. We found support for multiple niche polymorphism maintaining Bb diversity in nature and little evidence of temporal shifts in genotype dominance, as would be expected under negative frequency-dependent selection. Passerine birds support the circulation of several human invasive strains in the local tick population and harbor greater Bb genotypic diversity compared to white-footed mice. Mouse-adapted Bb genotypes exhibited longer persistence in individual mice compared to non-adapted genotypes and infection communities infecting individual mice preferentially became dominated by mouse-adapted genotypes over time. We posit that intraspecific variation in Bb host breadth and specificity helps maintain overall species fitness in response to transmission by a generalist vector. Because pathogen genotypes vary in host breadth and result in diverse human disease manifestations, our findings indicate that a more nuanced definition of ‘host competence’ incorporating local genotype frequency is warranted. 

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2. Cellular and immunological mechanisms influence host-adapted phenotypes in a vector-borne microparasite

   https://doi.org/10.1098/rspb.2021.2087  

   Lin, Yi-Pin; Tufts, Danielle M.; Combs, Matthew; Dupuis, Alan P.; Marcinkiewicz, Ashley L.; Hirsbrunner, Andrew D.; Diaz, Alexander J.; Stout, Jessica L.; Blom, Anna M.; Strle, Klemen; et al (February 2022, Proceedings of the Royal Society B: Biological Sciences)

   Predicting pathogen emergence and spillover risk requires understanding the determinants of a pathogens' host range and the traits involved in host competence. While host competence is often considered a fixed species-specific trait, it may be variable if pathogens diversify across hosts. Balancing selection can lead to maintenance of pathogen polymorphisms (multiple-niche-polymorphism; MNP). The causative agent of Lyme disease, Borrelia burgdorferi ( Bb ), provides a model to study the evolution of host adaptation, as some Bb strains defined by their outer surface protein C ( ospC ) genotype, are widespread in white-footed mice and others are associated with non-rodent vertebrates (e.g. birds). To identify the mechanisms underlying potential strain × host adaptation, we infected American robins and white-footed mice, with three Bb strains of different ospC genotypes. Bb burdens varied by strain in a host-dependent fashion, and strain persistence in hosts largely corresponded to Bb survival at early infection stages and with transmission to larvae (i.e. fitness). Early survival phenotypes are associated with cell adhesion, complement evasion and/or inflammatory and antibody-mediated removal of Bb, suggesting directional selective pressure for host adaptation and the potential role of MNP in maintaining OspC diversity. Our findings will guide future investigations to inform eco-evolutionary models of host adaptation for microparasites. 

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3. Comparative transcriptome analysis of Peromyscus leucopus and C3H mice infected with the Lyme disease pathogen

   https://doi.org/10.3389/fcimb.2023.1115350  

   Gaber, Alhussien M.; Mandric, Igor; Nitirahardjo, Caroline; Piontkivska, Helen; Hillhouse, Andrew E.; Threadgill, David W.; Zelikovsky, Alex; Rogovskyy, Artem S. (April 2023, Frontiers in Cellular and Infection Microbiology)

   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. 

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4. Host blood meal identity modifies vector gene expression and competency

   https://doi.org/10.1111/mec.16413  

   Ring, Kacie; Couper, Lisa I.; Sapiro, Anne L.; Yarza, Fauna; Yang, X. Frank; Clay, Keith; Mateusiak, Chase; Chou, Seemay; Swei, Andrea (January 2022, Molecular Ecology)

   A vector's susceptibility and ability to transmit a pathogen—termed vector competency—determines disease outcomes, yet the ecological factors influencing tick vector competency remain largely unknown. Ixodes pacificus, the tick vector of Borrelia burgdorferi (Bb) in the western U.S., feeds on rodents, birds, and lizards. Rodents and birds are reservoirs for Bb and infect juvenile ticks, while lizards are refractory to Bb and cannot infect feeding ticks. Additionally, the lizard bloodmeal contains borreliacidal properties, clearing previously infected feeding ticks of their Bb infection. Despite I. pacificus feeding on a range of hosts, it is undetermined how the host identity of the larval bloodmeal affects future nymphal vector competency. We experimentally evaluate the influence of larval host bloodmeal on Bb acquisition by nymphal I. pacificus. Larval I. pacificus were fed on either lizards or mice and after molting, nymphs were fed on Bb-infected mice. We found that lizard-fed larvae were significantly more likely to become infected with Bb during their next bloodmeal than mouse-fed larvae. We also conducted the first RNA-seq analysis on whole-bodied I. pacificus and found significant upregulation of tick antioxidants and antimicrobial peptides in the lizard-fed group. Our results indicate that the lizard bloodmeal significantly alters vector competency and gene regulation in ticks, highlighting the importance of host bloodmeal identity in vector-borne disease transmission and upends prior notions about the role of lizards in Lyme disease community ecology. 

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5. Ecological dynamics of blacklegged ticks, vertebrate hosts, and associated zoonotic pathogens in northeastern forests

   https://doi.org/10.1002/ecs2.70508  

   LaDeau, Shannon L; Oggenfuss, Kelly; Schmidt, Alexander; Thangamani, Saravanan; Ostfeld, Richard S (December 2025, Ecosphere)

   VanBael, S (Ed.)

   Abstract Specific host‐tick interactions in temperate forest systems influence variation in density and infection prevalence of nymphal blacklegged tick (Ixodes scapularis). The density of infected nymphs (DIN), which is the product of nymphal infection prevalence (NIP) and density of questing nymphs (DON), influences the risk of human exposure to tick‐borne pathogens. Questing nymphs (>2000) collected between 2014 and 2022 were screened for 16 zoonotic pathogens. More than a third (38.8%) of nymphs were infected with at least one pathogen, andBorrelia burgdorferi(the agent of Lyme disease) was detected in all six sampling locations and years. Pathogens includedBabesia microti(NIP = 21.4%),Bo. burgdorferi(19.3%),Anaplasma phagocytophilum(5.8%),Bo. miyamotoi(1.5%), Powassan virus (<0.01%), and two regionally emergentRickettsia(10 nymphs sampled in 2016 and 2021). Rates ofBa. microtiinfection were high relative to prior work, and coinfection withBo. burgdorferiincreased during the study period. White‐footed mouse (Peromyscus leucopus) and eastern chipmunk (Tamias striatus) are important zoonotic hosts in temperate forests. We evaluated how variation in host abundance and the number of larval ticks feeding per animal (larval burden) explained and predicted DIN, as well as DON and NIP independently. While both mouse abundance and mouse larval burden were positive predictors of DON in this study, their influence on NIP and DIN for commonly detected pathogens differed. Both mouse and chipmunk larval burden explained significant variation inBo. burgdorferiDIN, and larval burden on mice specifically improved prediction when observedBo. burgdorferiDIN was high. Chipmunk larval burden also predicted variance inBo. burgdorferiNIP and also explained significant variation inBa. microtiDIN. While observed host‐tick contact metrics improved predictive skill, underprediction was most evident when observed DIN or NIP was high. These results emphasize how tick‐borne zoonoses depend on a distribution of larval meals across a community of hosts. ForBo. burgdorferiin particular, NIP may be stabilized by tick‐feeding on a diverse host community. Thus, while large changes in mouse abundance may predict regional changes in DIN, local NIP in particular may be more responsive to shifts in larval feeding activity across the entire community of hosts. 

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