More Like this

1. Pathogen contingency loci and the evolution of host specificity: Simple sequence repeats mediate Bartonella adaptation to a wild rodent host

   https://doi.org/10.1371/journal.ppat.1012591  

   Rodríguez-Pastor, Ruth; Knossow, Nadav; Shahar, Naama; Hasik, Adam Z; Deatherage, Daniel E; Gutiérrez, Ricardo; Harrus, Shimon; Zaman, Luis; Lenski, Richard E; Barrick, Jeffrey E; et al (September 2024, PLOS Pathogens)

   Yue, Min (Ed.)

   Parasites, including pathogens, can adapt to better exploit their hosts on many scales, ranging from within an infection of a single individual to series of infections spanning multiple host species. However, little is known about how the genomes of parasites in natural communities evolve when they face diverse hosts. We investigated howBartonellabacteria that circulate in rodent communities in the dunes of the Negev Desert in Israel adapt to different species of rodent hosts. We propagated 15Bartonellapopulations through infections of either a single host species (Gerbillus andersoniorGerbillus pyramidum) or alternating between the two. After 20 rodent passages, strains withde novomutations replaced the ancestor in most populations. Mutations in two mononucleotide simple sequence repeats (SSRs) that caused frameshifts in the same adhesin gene dominated the evolutionary dynamics. They appeared exclusively in populations that encounteredG.andersoniand altered the dynamics of infections of this host. Similar SSRs in other genes are conserved and exhibit ON/OFF variation inBartonellaisolates from the Negev Desert dunes. Our results suggest that SSR-based contingency loci could be important not only for rapidly and reversibly generating antigenic variation to escape immune responses but that they may also mediate the evolution of host specificity. 

   more » « less
2. Estimating pathogen‐spillover risk using host–ectoparasite interactions

   https://doi.org/10.1002/ece3.11509  

   Brennan, Reilly_N; Paulson, Sally_L; Escobar, Luis_E (June 2024, Ecology and Evolution)

   Abstract Pathogen spillover corresponds to the transmission of a pathogen or parasite from an original host species to a novel host species, preluding disease emergence. Understanding the interacting factors that lead to pathogen transmission in a zoonotic cycle could help identify novel hosts of pathogens and the patterns that lead to disease emergence. We hypothesize that ecological and biogeographic factors drive host encounters, infection susceptibility, and cross‐species spillover transmission. Using a rodent–ectoparasite system in the Neotropics, with shared ectoparasite associations as a proxy for ecological interaction between rodent species, we assessed relationships between rodents using geographic range, phylogenetic relatedness, and ectoparasite associations to determine the roles of generalist and specialist hosts in the transmission cycle of hantavirus. A total of 50 rodent species were ranked on their centrality in a network model based on ectoparasites sharing. Geographic proximity and phylogenetic relatedness were predictors for rodents to share ectoparasite species and were associated with shorter network path distance between rodents through shared ectoparasites. The rodent–ectoparasite network model successfully predicted independent data of seven known hantavirus hosts. The model predicted five novel rodent species as potential, unrecognized hantavirus hosts in South America. Findings suggest that ectoparasite data, geographic range, and phylogenetic relatedness of wildlife species could help predict novel hosts susceptible to infection and possible transmission of zoonotic pathogens. Hantavirus is a high‐consequence zoonotic pathogen with documented animal‐to‐animal, animal‐to‐human, and human‐to‐human transmission. Predictions of new rodent hosts can guide active epidemiological surveillance in specific areas and wildlife species to mitigate hantavirus spillover transmission risk from rodents to humans. This study supports the idea that ectoparasite relationships among rodents are a proxy of host species interactions and can inform transmission cycles of diverse pathogens circulating in wildlife disease systems, including wildlife viruses with epidemic potential, such as hantavirus. 

   more » « less
3. Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association

   https://doi.org/10.1128/msystems.00488-22  

   Combs, Matthew; Marcinkiewicz, Ashley L.; Dupuis, Alan P.; Davis, April D.; Lederman, Patricia; Nowak, Tristan A.; Stout, Jessica L.; Strle, Klemen; Fingerle, Volker; Margos, Gabriele; et al (August 2022, mSystems)

   Gilbert, Jack A. (Ed.)

   ABSTRACT Host association—the selective adaptation of pathogens to specific host species—evolves through constant interactions between host and pathogens, leaving a lot yet to be discovered on immunological mechanisms and genomic determinants. The causative agents of Lyme disease (LD) are spirochete bacteria composed of multiple species of the Borrelia burgdorferi sensu lato complex, including B. burgdorferi ( Bb ), the main LD pathogen in North America—a useful model for the study of mechanisms underlying host-pathogen association. Host adaptation requires pathogens’ ability to evade host immune responses, such as complement, the first-line innate immune defense mechanism. We tested the hypothesis that different host-adapted phenotypes among Bb strains are linked to polymorphic loci that confer complement evasion traits in a host-specific manner. We first examined the survivability of 20 Bb strains in sera in vitro and/or bloodstream and tissues in vivo from rodent and avian LD models. Three groups of complement-dependent host-association phenotypes emerged. We analyzed complement-evasion genes, identified a priori among all strains and sequenced and compared genomes for individual strains representing each phenotype. The evolutionary history of ospC loci is correlated with host-specific complement-evasion phenotypes, while comparative genomics suggests that several gene families and loci are potentially involved in host association. This multidisciplinary work provides novel insights into the functional evolution of host-adapted phenotypes, building a foundation for further investigation of the immunological and genomic determinants of host association. IMPORTANCE Host association is the phenotype that is commonly found in many pathogens that preferential survive in particular hosts. The Lyme disease (LD)-causing agent, B. burgdorferi ( Bb ), is an ideal model to study host association, as Bb is mainly maintained in nature through rodent and avian hosts. A widespread yet untested concept posits that host association in Bb strains is linked to Bb functional genetic variation conferring evasion to complement, an innate defense mechanism in vertebrate sera. Here, we tested this concept by grouping 20 Bb strains into three complement-dependent host-association phenotypes based on their survivability in sera and/or bloodstream and distal tissues in rodent and avian LD models. Phylogenomic analysis of these strains further correlated several gene families and loci, including ospC , with host-specific complement-evasion phenotypes. Such multifaceted studies thus pave the road to further identify the determinants of host association, providing mechanistic insights into host-pathogen interaction. 

   more » « less
4. 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. 

   more » « less
5. Structural evolution of an immune evasion determinant shapes Lyme borreliae host tropism

   https://doi.org/10.1101/2022.09.13.507797  

   Marcinkiewicz AL; Brangulis K; Dupuis AP II; Hart TH; Zamba-Campero M; Nowak TA; Stout JL; Akopjana I; Kazaks A; Bogans J; et al (September 2022, bioRxiv)

   The preferential adaptation of pathogens to specific hosts, known as host tropism, evolves through host-pathogen interactions. Transmitted by ticks and maintained primarily in rodents and birds, the Lyme disease-causing bacterium Borrelia burgdorferi (Bb) is an ideal model to investigate the mechanisms of host tropism. In order to survive in hosts and escape complement-mediated clearance, a first-line host immune defense, Bb produces the outer surface protein CspZ that binds to the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants vary in human FH-binding ability. Together with the FH polymorphisms found amongst vertebrate hosts, these findings raise a hypothesis that minor sequence variation in a bacterial outer surface protein confers dramatic differences in host- specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ-human FH complex, identifying a minor change localized in the FH-binding interface, and uncovered that the bird and rodent FH-specific binding activity of different CspZ variants directly impacts infectivity. Swapping the divergent loop region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. By employing phylogenetic tree thinking, we correlated these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ lineages and elucidated evolutionary mechanisms driving CspZ emergence. Our multidisciplinary work provides mechanistic insights into how a single, short pathogen protein motif could greatly impact host tropism. 

   more » « less