Sequence Variation of Rare Outer Membrane Protein beta-Barrel
Domains in Clinical Strains Provides Insights into the
Evolution of Treponema pallidum subsp. pallidum, the Syphilis
Spirochete

J 2018

Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete

KUMAR, Sanjiv), Melissa J. CAIMANO, Arvind ANAND, Abhishek DEY, Kelly L. HAWLEY et. al.

Basic information

Original name

Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete

Authors

KUMAR, Sanjiv) (840 United States of America), Melissa J. CAIMANO (840 United States of America), Arvind ANAND (840 United States of America), Abhishek DEY (840 United States of America), Kelly L. HAWLEY (840 United States of America), Morgan E. LEDOYT (840 United States of America), Carson J. LA VAKE (840 United States of America), Adriana R. CRUZ (170 Colombia), Lady G. RAMIREZ (170 Colombia), Lenka PAŠTĚKOVÁ (203 Czech Republic, belonging to the institution), Irina BEZSONOVA (840 United States of America), David ŠMAJS (203 Czech Republic, belonging to the institution), Juan C. SALAZAR (840 United States of America) and Justin D. RADOLF (840 United States of America, guarantor)

Edition

MBIO, WASHINGTON, AMER SOC MICROBIOLOGY, 2018, 2150-7511

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10606 Microbiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 6.747

RIV identification code

RIV/00216224:14110/18:00101706

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1128/mBio.01006-18

UT WoS

000454748900021

Keywords in English

Treponema pallidum; molecular subtyping; outer membrane proteins; spirochetes; syphilis

Abstract

V originále

In recent years, considerable progress has been made in topologically and functionally characterizing integral outer membrane proteins (OMPs) of Treponerna pallidum subspecies pallidum, the syphilis spirochete, and identifying its surface-exposed p-barrel domains. Extracellular loops in OMPs of Gram-negative bacteria are known to be highly variable. We examined the sequence diversity of beta-barrel-encoding regions of tprC, tprD, and bamA in 31 specimens from Cali, Colombia; San Francisco, California; and the Czech Republic and compared them to allelic variants in the 41 reference genomes in the NCBI database. To establish a phylogenetic framework, we used T. pallidum 0548 (tp0548) genotyping and tp0558 sequences to assign strains to the Nichols or SS14 clades. We found that (i) beta-barrels in clinical strains could be grouped according to allelic variants in T. pallidum subsp. pallidum reference genomes; (ii) for all three OMP loci, clinical strains within the Nichols or SS14 clades often harbored beta-barrel variants that differed from the Nichols and SS14 reference strains; and (iii) OMP variable regions often reside in predicted extracellular loops containing B-cell epitopes. On the basis of structural models, nonconservative amino acid substitutions in predicted transmembrane beta-strands of T. pallidum repeat C (TprC) and TprD2 could give rise to functional differences in their porin channels. OMP profiles of some clinical strains were mosaics of different reference strains and did not correlate with results from enhanced molecular typing. Our observations suggest that human host selection pressures drive T. pallidum subsp. pallidum OMP diversity and that genetic exchange contributes to the evolutionary biology of T. pallidum subsp. pallidum. They also set the stage for topology-based analysis of antibody responses to OMPs and help frame strategies for syphilis vaccine development. IMPORTANCE Despite recent progress characterizing outer membrane proteins (OMPs) of Treponema pallidum, little is known about how their surface-exposed, beta-barrel-forming domains vary among strains circulating within high-risk populations. In this study, sequences for the beta-barrel-encoding regions of three OMP loci, tprC, tprD, and bamA, in T. pallidum subsp. pallidum isolates from a large number of patient specimens from geographically disparate sites were examined. Structural models predict that sequence variation within beta-barrel domains occurs predominantly within predicted extracellular loops. Amino acid substitutions in predicted transmembrane strands that could potentially affect porin channel function were also noted. Our findings suggest that selection pressures exerted within human populations drive T. pallidum subsp. pallidum OMP diversity and that recombination at OMP loci contributes to the evolutionary biology of syphilis spirochetes. These results also set the stage for topology-based analysis of antibody responses that promote clearance of T. pallidum subsp. pallidum and frame strategies for vaccine development based upon conserved OMP extracellular loops.

Links

GA17-25455S, research and development project

Name: Studium genomů patogenních treponem na základě analýzy jednotlivých buněk

Investor: Czech Science Foundation

NV17-31333A, research and development project

Name: Vývoj nového typovacího systému pro původce syfilis, Treponema pallidum subsp. pallidum, zaměřeného na proteomické rozdíly

Citovat

KUMAR, Sanjiv), Melissa J. CAIMANO, Arvind ANAND, Abhishek DEY, Kelly L. HAWLEY, Morgan E. LEDOYT, Carson J. LA VAKE, Adriana R. CRUZ, Lady G. RAMIREZ, Lenka PAŠTĚKOVÁ, Irina BEZSONOVA, David ŠMAJS, Juan C. SALAZAR and Justin D. RADOLF. Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete. MBIO. WASHINGTON: AMER SOC MICROBIOLOGY, 2018, vol. 9, No 3, p. 1-20. ISSN 2150-7511. Available from: https://dx.doi.org/10.1128/mBio.01006-18.

@article{1498477,
   author = {Kumar, Sanjiv) and Caimano, Melissa J. and Anand, Arvind and Dey, Abhishek and Hawley, Kelly L. and LeDoyt, Morgan E. and La Vake, Carson J. and Cruz, Adriana R. and Ramirez, Lady G. and Paštěková, Lenka and Bezsonova, Irina and Šmajs, David and Salazar, Juan C. and Radolf, Justin D.},
   article_location = {WASHINGTON},
   article_number = {3},
   doi = {http://dx.doi.org/10.1128/mBio.01006-18},
   keywords = {Treponema pallidum; molecular subtyping; outer membrane proteins; spirochetes; syphilis},
   language = {eng},
   issn = {2150-7511},
   journal = {MBIO},
   title = {Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete},
   volume = {9},
   year = {2018}
}

TY  - JOUR
ID  - 1498477
AU  - Kumar, Sanjiv) - Caimano, Melissa J. - Anand, Arvind - Dey, Abhishek - Hawley, Kelly L. - LeDoyt, Morgan E. - La Vake, Carson J. - Cruz, Adriana R. - Ramirez, Lady G. - Paštěková, Lenka - Bezsonova, Irina - Šmajs, David - Salazar, Juan C. - Radolf, Justin D.
PY  - 2018
TI  - Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete
JF  - MBIO
VL  - 9
IS  - 3
SP  - 1-20
EP  - 1-20
PB  - AMER SOC MICROBIOLOGY
SN  - 21507511
KW  - Treponema pallidum
KW  - molecular subtyping
KW  - outer membrane proteins
KW  - spirochetes
KW  - syphilis
N2  - In recent years, considerable progress has been made in topologically and functionally characterizing integral outer membrane proteins (OMPs) of Treponerna pallidum subspecies pallidum, the syphilis spirochete, and identifying its surface-exposed p-barrel domains. Extracellular loops in OMPs of Gram-negative bacteria are known to be highly variable. We examined the sequence diversity of beta-barrel-encoding regions of tprC, tprD, and bamA in 31 specimens from Cali, Colombia; San Francisco, California; and the Czech Republic and compared them to allelic variants in the 41 reference genomes in the NCBI database. To establish a phylogenetic framework, we used T. pallidum 0548 (tp0548) genotyping and tp0558 sequences to assign strains to the Nichols or SS14 clades. We found that (i) beta-barrels in clinical strains could be grouped according to allelic variants in T. pallidum subsp. pallidum reference genomes; (ii) for all three OMP loci, clinical strains within the Nichols or SS14 clades often harbored beta-barrel variants that differed from the Nichols and SS14 reference strains; and (iii) OMP variable regions often reside in predicted extracellular loops containing B-cell epitopes. On the basis of structural models, nonconservative amino acid substitutions in predicted transmembrane beta-strands of T. pallidum repeat C (TprC) and TprD2 could give rise to functional differences in their porin channels. OMP profiles of some clinical strains were mosaics of different reference strains and did not correlate with results from enhanced molecular typing. Our observations suggest that human host selection pressures drive T. pallidum subsp. pallidum OMP diversity and that genetic exchange contributes to the evolutionary biology of T. pallidum subsp. pallidum. They also set the stage for topology-based analysis of antibody responses to OMPs and help frame strategies for syphilis vaccine development. IMPORTANCE Despite recent progress characterizing outer membrane proteins (OMPs) of Treponema pallidum, little is known about how their surface-exposed, beta-barrel-forming domains vary among strains circulating within high-risk populations. In this study, sequences for the beta-barrel-encoding regions of three OMP loci, tprC, tprD, and bamA, in T. pallidum subsp. pallidum isolates from a large number of patient specimens from geographically disparate sites were examined. Structural models predict that sequence variation within beta-barrel domains occurs predominantly within predicted extracellular loops. Amino acid substitutions in predicted transmembrane strands that could potentially affect porin channel function were also noted. Our findings suggest that selection pressures exerted within human populations drive T. pallidum subsp. pallidum OMP diversity and that recombination at OMP loci contributes to the evolutionary biology of syphilis spirochetes. These results also set the stage for topology-based analysis of antibody responses that promote clearance of T. pallidum subsp. pallidum and frame strategies for vaccine development based upon conserved OMP extracellular loops.
ER  -

KUMAR, Sanjiv), Melissa J. CAIMANO, Arvind ANAND, Abhishek DEY, Kelly L. HAWLEY, Morgan E. LEDOYT, Carson J. LA VAKE, Adriana R. CRUZ, Lady G. RAMIREZ, Lenka PAŠTĚKOVÁ, Irina BEZSONOVA, David ŠMAJS, Juan C. SALAZAR and Justin D. RADOLF. Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete. \textit{MBIO}. WASHINGTON: AMER SOC MICROBIOLOGY, 2018, vol.~9, No~3, p.~1-20. ISSN~2150-7511. Available from: https://dx.doi.org/10.1128/mBio.01006-18.

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