FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease

Camire, Andrew C.; O’Bier, Nathaniel S.; Patel, Dhara T; Cramer, Nicholas A.; Straubinger, Reinhard K.; Breitschwerdt, Edward B.; Funk, Rebecca A.; Marconi, Richard T.

doi:10.1128/iai.00364-22

Cited by 2 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, after covalent modification by a fatty acid at its N-terminal Cys residue, the protein can be targeted into the periplasmic side of the cytoplasmic membrane, the periplasmic side of the outer membrane, or the external side of the outer membrane [ 12 ]. To clarify the exact location of the PFam12 proteins, prior experimental evidence indicated that FtlE is most likely a periplasmic inner membrane-attached protein, while FtlA, FtlB and FtlCare surface-exposed lipoproteins [ 23 , 24 , 27 ]. Since the lipoprotein signal sequence region in spirochetes may exhibit comparatively high variability, the PFam12 member FtlD was not included in any of the previous studies for lipoprotein localization [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

“…In the current study we focused on the paralogous gene family 12 (PFam12), which contains five members (BB0844, BBG01, BBH37, BBJ08, and BBK01) that do not demonstrate meaningful sequence identity with proteins from any other organism which would allow us to judge the functions of these proteins. It is known that PFam12 members are surface-exposed and highly immunogenic lipoproteins that are upregulated as the tick starts the blood meal [ 8 , 13 , 14 , 23 – 27 ]. In a recent article studying the antigenicity and immunogenicity of PFam12 members, it was suggested to rename the proteins as f amily t welve l ipoproteins (Ftl) FtlA (BBK01), FtlB (BBG01), FtlC (BBH37), and FtlD (BBJ08) [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is known that PFam12 members are surface-exposed and highly immunogenic lipoproteins that are upregulated as the tick starts the blood meal [ 8 , 13 , 14 , 23 – 27 ]. In a recent article studying the antigenicity and immunogenicity of PFam12 members, it was suggested to rename the proteins as f amily t welve l ipoproteins (Ftl) FtlA (BBK01), FtlB (BBG01), FtlC (BBH37), and FtlD (BBJ08) [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Members of the paralogous gene family 12 from the Lyme disease agent Borrelia burgdorferi are non-specific DNA-binding proteins

Brangulis,

Akopjana,

Drunka

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Lyme disease is the most prevalent vector-borne infectious disease in Europe and the USA. Borrelia burgdorferi, as the causative agent of Lyme disease, is transmitted to the mammalian host during the tick blood meal. To adapt to the different encountered environments, Borrelia has adjusted the expression pattern of various, mostly outer surface proteins. The function of most B. burgdorferi outer surface proteins remains unknown. We determined the crystal structure of a previously uncharacterized B. burgdorferi outer surface protein BBK01, known to belong to the paralogous gene family 12 (PFam12) as one of its five members. PFam12 members are shown to be upregulated as the tick starts its blood meal. Structural analysis of BBK01 revealed similarity to the coiled coil domain of structural maintenance of chromosomes (SMC) protein family members, while functional studies indicated that all PFam12 members are non-specific DNA-binding proteins. The residues involved in DNA binding were identified and probed by site-directed mutagenesis. The combination of SMC-like proteins being attached to the outer membrane and exposed to the environment or located in the periplasm, as observed in the case of PFam12 members, and displaying the ability to bind DNA, represents a unique feature previously not observed in bacteria.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Members of the paralogous gene family 12 from the Lyme disease agent Borrelia burgdorferi are non-specific DNA-binding proteins

Brangulis,

Akopjana,

Drunka

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

show abstract

Borreliella burgdorferi factor H-binding proteins are not required for serum resistance and infection in mammals

Cramer,

Socarras,

Earl

et al. 2024

Infect Immun

View full text Add to dashboard Cite

The causative agent of Lyme disease (LD), Borreliella burgdorferi , binds factor H (FH) and other complement regulatory proteins to its surface. B. burgdorferi B31 (type strain) encodes five FH-binding proteins (FHBPs): CspZ, CspA, and the OspE paralogs OspE BBN38 , OspE BBL39 , and OspE BBP38 . This study assessed potential correlations between the production of individual FHBPs, FH-binding ability, and serum resistance using a panel of infectious B. burgdorferi clonal populations recovered from dogs. FHBP production was assessed in cultivated spirochetes and by antibody responses in naturally infected humans, dogs, and eastern coyotes (wild canids). FH binding specificity and sensitivity to dog and human serum were also assessed and compared. No correlation was observed between the production of individual FHBPs and FH binding with serum resistance, and CspA was determined to not be produced in animals. Notably, one or more clones isolated from dogs lacked CspZ or the OspE proteins (a finding confirmed by genome sequence determination) and did not bind FH derived from canines. The data presented do not support a correlation between FH binding and the production of individual FHBPs with serum resistance and infectivity. In addition, the limited number and polymorphic nature of cp32s in B. burgdorferi clone DRI85A that were identified through genome sequencing suggest no strict requirement for a defined set of these replicons for infectivity. This study reveals that the immune evasion mechanisms employed by B. burgdorferi are diverse, complex, and yet to be fully defined.

show abstract

FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease

Cited by 2 publications

References 44 publications

Members of the paralogous gene family 12 from the Lyme disease agent Borrelia burgdorferi are non-specific DNA-binding proteins

Members of the paralogous gene family 12 from the Lyme disease agent Borrelia burgdorferi are non-specific DNA-binding proteins

Borreliella burgdorferi factor H-binding proteins are not required for serum resistance and infection in mammals

Contact Info

Product

Resources

About