Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-08-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msystems.00488-22 |
| _version_ | 1797999650341388288 |
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| author | Matthew Combs Ashley L. Marcinkiewicz Alan P. Dupuis April D. Davis Patricia Lederman Tristan A. Nowak Jessica L. Stout Klemen Strle Volker Fingerle Gabriele Margos Alexander T. Ciota Maria A. Diuk-Wasser Sergios-Orestis Kolokotronis Yi-Pin Lin |
| author_facet | Matthew Combs Ashley L. Marcinkiewicz Alan P. Dupuis April D. Davis Patricia Lederman Tristan A. Nowak Jessica L. Stout Klemen Strle Volker Fingerle Gabriele Margos Alexander T. Ciota Maria A. Diuk-Wasser Sergios-Orestis Kolokotronis Yi-Pin Lin |
| author_sort | Matthew Combs |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T11:08:03Z |
| format | Article |
| id | doaj.art-007b6c3c4e82410d957d1a2687bfe3e4 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-04-11T11:08:03Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-007b6c3c4e82410d957d1a2687bfe3e42022-12-22T04:28:05ZengAmerican Society for MicrobiologymSystems2379-50772022-08-017410.1128/msystems.00488-22Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host AssociationMatthew Combs0Ashley L. Marcinkiewicz1Alan P. Dupuis2April D. Davis3Patricia Lederman4Tristan A. Nowak5Jessica L. Stout6Klemen Strle7Volker Fingerle8Gabriele Margos9Alexander T. Ciota10Maria A. Diuk-Wasser11Sergios-Orestis Kolokotronis12Yi-Pin Lin13Department of Ecology, Evolution, and Environmental Biology, Columbia University, New York, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USAGerman National Reference Centre for Borrelia, Bavarian Health and Food Safety Authority, Oberschleissheim, GermanyGerman National Reference Centre for Borrelia, Bavarian Health and Food Safety Authority, Oberschleissheim, GermanyDivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USADepartment of Ecology, Evolution, and Environmental Biology, Columbia University, New York, New York, USADepartment of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, New York, USADivision of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/msystems.00488-22host associationBorreliacomplementphylogenomicsplasmid diversity |
| spellingShingle | Matthew Combs Ashley L. Marcinkiewicz Alan P. Dupuis April D. Davis Patricia Lederman Tristan A. Nowak Jessica L. Stout Klemen Strle Volker Fingerle Gabriele Margos Alexander T. Ciota Maria A. Diuk-Wasser Sergios-Orestis Kolokotronis Yi-Pin Lin Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association mSystems host association Borrelia complement phylogenomics plasmid diversity |
| title | Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association |
| title_full | Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association |
| title_fullStr | Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association |
| title_full_unstemmed | Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association |
| title_short | Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association |
| title_sort | phylogenomic diversity elucidates mechanistic insights into lyme borreliae host association |
| topic | host association Borrelia complement phylogenomics plasmid diversity |
| url | https://journals.asm.org/doi/10.1128/msystems.00488-22 |
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