Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association

Combs, Matthew; Marcinkiewicz, Ashley L.; Dupuis, Alan P.; Davis, April; Lederman, Patricia; Nowak, Tristan A.; Stout, Jessica; Strle, Klemen; Fingerle, Volker; Margos, Gabriele; Ciota, Alexander T.; Diuk‐Wasser, Maria A.; Kolokotronis, Sergios‐Orestis; Lin, Yi‐Pin

doi:10.1128/msystems.00488-22

Cited by 9 publications

(25 citation statements)

References 106 publications

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“…Some Lyme borreliae species or strains carry determinants that promoting host-specific phenotypes that differ from the known host range of these species or strains (36, 60–62). For example, the B. burgdorferi strain 297 is highly infectious in mice, but its CspZ loop-structures are identical to those in CspZ B379 from the strain B379 that is not mouse adapted (36, 62).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the B. burgdorferi strain 297 is highly infectious in mice, but its CspZ loop-structures are identical to those in CspZ B379 from the strain B379 that is not mouse adapted (36, 62). This reflects the fact that most conclusions from this study were drawn by using spirochete strains with the same genetic background but producing the CspZ variants of interest, which may not account for polygenic contributions of other proteins in different strains (36). One possibility that addresses this discrepancy is that host-adapted phenotypes are conferred by not only CspZ but other anti- complement proteins, and the functional contribution from each of these proteins differ (and/or are host-dependent).…”

Section: Discussionmentioning

confidence: 99%

“…Mouse FH was purchased from MyBiosource (San Diego, CA). Quail FH and recombinant OmCI proteins were generated as described previously (24, 32, 36, 39). The mouse and quail sera were obtained from Southern Biotech, Inc (Birmingham, AL) and Canola Live Poultry Market (Brooklyn, NY), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…To generate recombinant CspZ proteins for crystallization, cspZ B379 (GenBank: FJ911671.1) and cspZ B408 (GenBank: FJ911677.1) were amplified by PCR from the genomic DNA of B. burgdorferi strain B379 and B408 using the primers listed in Table S8 . Note that B408 has two copies of cspZ , but they are functionally identical with only a single synonymous SNP at nucleotide 699 (36, 78). Based on the prediction by SignalP 4.1 (79) and according to our previous structural data from CspZ B31 (30), the lipoprotein signal peptide (residues 1-22) was excluded from the amplified gene.…”

Section: Methodsmentioning

confidence: 99%

“…CspZ production and FH-binding on spirochete surface were determined as described (24), including blood-treatment to induce the production of CspZ (32). To determine the levels of mouse C5b-9 or quail C8 deposition on the surface of spirochetes, mouse or quail sera were incubated with 1x10 7 spirochetes in PBS at a final concentration of 20% at 25°C for one hour and the detection procedure has been described previously (36). Basically, after incubation, spirochetes were washed then resuspended in HBSC-DB (25mM Hepes acid, 150mM sodium chloride, 1mM MnCl 2 , 1mM MgCl 2 , 0.25mM CaCl 2 , 0.1% glucose, and 0.2% BSA).…”

Section: Methodsmentioning

confidence: 99%

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Structural evolution of an immune evasion determinant shapes Lyme borreliae host tropism

Marcinkiewicz

Brangulis

Dupuis

et al. 2022

Preprint

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Lyme disease presents a suitable model for the investigation of host tropism – a pathogen’s ability to colonize and survive in different host species – since its causative agent, the spirochete Borrelia burgdorferi (Bb) is transmitted by ticks and maintained in rodent and bird reservoir hosts. In order to survive in vertebrates and escape from killing by complement, a first-line host immune defense, Bb produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to promote infection. Protein sequence conservation seems to be linked to FH-binding activity divergence, raising the hypothesis that even minor variation can confer host-specific, FH-binding-mediated infectivity. Our work shows that that this minor variation is located in a loop in the CspZ protein localized in the CspZ-FH binding interface. Our functional experiments prove that this loop promotes bird- or rodent-specific FH-binding activity and infectivity. Swapping loops between rodent- and bird-associated CspZ variants alters their capability to confer host-specific dissemination. We further investigated the evolutionary mechanisms driving the emergence of the CspZ loop-mediated, host-dependent complement evasion. This multifaceted work demonstrates how a single, short protein motif can significantly impact host tropism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Structural evolution of an immune evasion determinant shapes Lyme borreliae host tropism

Marcinkiewicz

Brangulis

Dupuis

et al. 2022

Preprint

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Unprecedented genetic variability of PFam54 paralogs among Eurasian Lyme borreliosis‐causing spirochetes

Wülbern,

Windorfer,

Sato

et al. 2024

Ecology and Evolution

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Lyme borreliosis (LB) is the most common vector‐borne disease in the Northern Hemisphere caused by spirochetes belonging to the Borrelia burgdorferi sensu lato (Bbsl) complex. Borrelia spirochetes circulate in obligatory transmission cycles between tick vectors and different vertebrate hosts. To successfully complete this complex transmission cycle, Bbsl encodes for an arsenal of proteins including the PFam54 protein family with known, or proposed, influences to reservoir host and/or vector adaptation. Even so, only fragmentary information is available regarding the naturally occurring level of variation in the PFam54 gene array especially in relation to Eurasian‐distributed species. Utilizing whole genome data from isolates (n = 141) originated from three major LB‐causing Borrelia species across Eurasia (B. afzelii, B. bavariensis, and B. garinii), we aimed to characterize the diversity of the PFam54 gene array in these isolates to facilitate understanding the evolution of PFam54 paralogs on an intra‐ and interspecies level. We found an extraordinarily high level of variation in the PFam54 gene array with 39 PFam54 paralogs belonging to 23 orthologous groups including five novel paralogs. Even so, the gene array appears to have remained fairly stable over the evolutionary history of the studied Borrelia species. Interestingly, genes outside Clade IV, which contains genes encoding for proteins associated with Borrelia pathogenesis, more frequently displayed signatures of diversifying selection between clades that differ in hypothesized vector or host species. This could suggest that non‐Clade IV paralogs play a more important role in host and/or vector adaptation than previously expected, which would require future lab‐based studies to validate.

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Conformational dynamics of complement protease C1r inhibitor proteins from Lyme disease– and relapsing fever–causing spirochetes

Roy

Booth

Powell-Pierce

et al. 2023

Journal of Biological Chemistry

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Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association

Cited by 9 publications

References 106 publications

Structural evolution of an immune evasion determinant shapes Lyme borreliae host tropism

Structural evolution of an immune evasion determinant shapes Lyme borreliae host tropism

Unprecedented genetic variability of PFam54 paralogs among Eurasian Lyme borreliosis‐causing spirochetes

Conformational dynamics of complement protease C1r inhibitor proteins from Lyme disease– and relapsing fever–causing spirochetes

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