Antibody Response to the Sneathia vaginalis Cytopathogenic Toxin A during Pregnancy.

Zion T McCoy, Myrna G Serrano, Laahirie Edupuganti, Katherine M Spaine, David J Edwards, Gregory A Buck, Kimberly K Jefferson
Author Information
  1. Zion T McCoy: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA.
  2. Myrna G Serrano: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA.
  3. Laahirie Edupuganti: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA.
  4. Katherine M Spaine: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA.
  5. David J Edwards: Center for Microbiome Engineering and Data Analysis, Virginia Commonwealth University, Richmond, VA.
  6. Gregory A Buck: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA.
  7. Kimberly K Jefferson: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA.

Abstract

Sneathia vaginalis is a Gram-negative vaginal species that is associated with pregnancy complications. It produces cytopathogenic toxin A (CptA), a pore-forming toxin. To determine whether CptA is expressed in vivo and to examine the mucosal Ab response to the toxin, we examined human midvaginal swab samples obtained during pregnancy for IgM, IgA, and IgG Abs with CptA affinity. This subcohort study included samples from 93 pregnant people. S. vaginalis relative abundance was available through 16S rRNA survey. There were 22 samples from pregnancies that resulted in preterm birth in which S. vaginalis relative abundance was <0.005%, 22 samples from pregnancies that resulted in preterm birth with S. vaginalis ≥0.005%, 24 samples from pregnancies that resulted in term birth with S. vaginalis <0.005%, and 25 samples from pregnancies that resulted in term birth with S. vaginalis ≥0.005%. IgM, IgA, and IgG with affinity for CptA were assessed by ELISA. The capacity for the samples to neutralize CptA was quantified by hemolysis assay. All three Ab isotypes were detectable within different subsets of the samples. There was no significant association between relative abundance of S. vaginalis and the presence of any Ab isotype. The majority of vaginal swab samples containing detectable levels of anti-CptA Abs neutralized the hemolytic activity of CptA, with the strongest correlation between IgA and neutralizing activity. These results demonstrate that S. vaginalis produces CptA in vivo and that CptA is recognized by the host immune defenses, resulting in the production of Abs with toxin-neutralizing ability.

References

  1. Cytokine. 2021 Jan;137:155316 [PMID: 33032107]
  2. BMC Genomics. 2012;13 Suppl 8:S17 [PMID: 23282177]
  3. J Reprod Med. 1989 Apr;34(4):292-4 [PMID: 2715991]
  4. Nat Med. 2019 Jun;25(6):1012-1021 [PMID: 31142849]
  5. Annu Rev Microbiol. 2012;66:371-89 [PMID: 22746335]
  6. Nat Med. 2019 Jun;25(6):1001-1011 [PMID: 31142850]
  7. Int J Syst Evol Microbiol. 2019 Jun;71(3): [PMID: 33616512]
  8. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7 [PMID: 20534435]
  9. Front Med (Lausanne). 2019 Sep 10;6:201 [PMID: 31552254]
  10. Semin Fetal Neonatal Med. 2016 Apr;21(2):100-5 [PMID: 26778525]
  11. BMC Bioinformatics. 2016 Dec 1;17(1):491 [PMID: 27905885]
  12. J Matern Fetal Neonatal Med. 2015 Aug;28(12):1394-409 [PMID: 25190175]
  13. Crit Rev Microbiol. 2021 Aug;47(4):517-542 [PMID: 33823747]
  14. J Bacteriol. 2020 Jun 9;202(13): [PMID: 32291280]
  15. PLoS One. 2023 May 4;18(5):e0284349 [PMID: 37141247]
  16. Science. 2014 Aug 15;345(6198):760-5 [PMID: 25124429]
  17. J Clin Microbiol. 2004 Dec;42(12):5940-3 [PMID: 15583348]
  18. New Microbes New Infect. 2023 Mar 21;53:101112 [PMID: 37065965]
  19. Paediatr Perinat Epidemiol. 2014 Mar;28(2):88-96 [PMID: 24405280]
  20. J Clin Microbiol. 2003 Jan;41(1):435-8 [PMID: 12517887]
  21. Front Immunol. 2014 Dec 09;5:624 [PMID: 25538708]
  22. Access Microbiol. 2021 Dec 09;3(12):000290 [PMID: 35024552]
  23. Semin Fetal Neonatal Med. 2012 Feb;17(1):2-11 [PMID: 22137615]
  24. PLoS One. 2008 Aug 26;3(8):e3056 [PMID: 18725970]
  25. BMC Genomics. 2012;13 Suppl 8:S4 [PMID: 23281612]
  26. Clin Perinatol. 2011 Sep;38(3):385-406 [PMID: 21890015]
  27. Lancet. 2008 Jan 5;371(9606):75-84 [PMID: 18177778]

Grants

  1. R21 AI166168/NIAID NIH HHS
  2. U54 HD080784/NICHD NIH HHS

MeSH Term

Infant, Newborn
Pregnancy
Female
Humans
Premature Birth
Antibody Formation
RNA, Ribosomal, 16S
Immunoglobulin G
Immunoglobulin M
Immunoglobulin A
Ethylamines

Chemicals

RNA, Ribosomal, 16S
2-(4-chlorophenylthio)triethylamine
Immunoglobulin G
Immunoglobulin M
Immunoglobulin A
Ethylamines

Word Cloud

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