Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Inactivated Vibrio cholerae Strains That Express TcpA via the toxT-139F Allele Induce Antibody Responses against TcpA

  • Eun Jin Kim (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Jonghyun Bae (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Young-Jun Ju (Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Do-Bin Ju (Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Donghyun Lee (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Seonghyeon Son (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Hunseok Choi (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Thandavarayan Ramamurthy (ICMR-National Institute of Cholera and Enteric Diseases) ;
  • Cheol-Heui Yun (Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Dong Wook Kim (Department of Pharmacy, College of Pharmacy, Hanyang University)
  • Received : 2020.09.01
  • Accepted : 2022.10.06
  • Published : 2022.11.28
Download PDF
⟨ Previous Next ⟩

Abstract

Cholera remains a major global public health problem, for which oral cholera vaccines (OCVs) being a valuable strategy. Patients, who have recovered from cholera, develop antibody responses against LPS, cholera toxin (CT), toxin-coregulated pilus (TCP) major subunit A (TcpA) and other antigens; thus, these responses are potentially important contributors to immunity against Vibrio cholerae infection. However, assessments of the efficacy of current OCVs, especially inactivated OCVs, have focused primarily on O-antigen-specific antibody responses, suggesting that more sophisticated strategies are required for inactivated OCVs to induce immune responses against TCP, CT, and other antigens. Previously, we have shown that the toxT-139F allele enables V. cholerae strains to produce CT and TCP under simple laboratory culture conditions. Thus, we hypothesized that V. cholerae strains that express TCP via the toxT-139F allele induce TCP-specific antibody responses. As anticipated, V. cholerae strains that expressed TCP through the toxT-139F allele elicited antibody responses against TCP when the inactivated bacteria were delivered via a mouse model. We have further developed TCP-expressing V. cholerae strains that have been used in inactivated OCVs and shown that they effect an antibody response against TcpA in vivo, suggesting that V. cholerae strains with the toxT-139F allele are excellent candidates for cholera vaccines.

Keywords

Acknowledgement

This work was supported by grants NRF-2021R1A2C1010857 and NRF-2020R1C1C1009992 from the National Research Foundation (NRF) of Korea, and Institute of Information & Communications Technology Planning & Evaluation (IITP) grant No. 2020-0-01343 funded by Ministry of Science and ICT (MSIT) of Korea.

References

  1. Clemens JD, Nair GB, Ahmed T, Qadri F, Holmgren J. 2017. Cholera. Lancet 390: 1539-1549. https://doi.org/10.1016/S0140-6736(17)30559-7
  2. Koch R. 1884. An address on cholera and its Bacillus. Br. Med. J. 2: 453-459. https://doi.org/10.1136/bmj.2.1236.453
  3. Kaper JB, Morris JG, Jr., Levine MM. 1995. Cholera. Clin. Microbiol. Rev. 8: 48-86. https://doi.org/10.1128/CMR.8.1.48
  4. Mutreja A, Kim DW, Thomson NR, Connor TR, Lee JH, Kariuki S, et al. 2011. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 477: 462-465. https://doi.org/10.1038/nature10392
  5. Safa A, Nair GB, Kong RY. 2010. Evolution of new variants of Vibrio cholerae O1. Trends Microbiol. 18: 46-54. https://doi.org/10.1016/j.tim.2009.10.003
  6. Kim EJ, Lee CH, Nair GB, Kim DW. 2015. Whole-genome sequence comparisons reveal the evolution of Vibrio cholerae O1. Trends Microbiol. 23: 479-489.
  7. Herrington DA, Hall RH, Losonsky G, Mekalanos JJ, Taylor RK, Levine MM. 1988. Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J. Exp. Med. 168: 1487-1492. https://doi.org/10.1084/jem.168.4.1487
  8. Lim MS, Ng D, Zong Z, Arvai AS, Taylor RK, Tainer JA, et al. 2010. Vibrio cholerae El Tor TcpA crystal structure and mechanism for pilus-mediated microcolony formation. Mol. Microbiol. 77: 755-770. https://doi.org/10.1111/j.1365-2958.2010.07244.x
  9. Krebs SJ, Taylor RK. 2011. Protection and attachment of Vibrio cholerae mediated by the toxin-coregulated pilus in the infant mouse model. J. Bacteriol. 193: 5260-5270. https://doi.org/10.1128/JB.00378-11
  10. Waldor MK, Mekalanos JJ. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272: 1910-1914. https://doi.org/10.1126/science.272.5270.1910
  11. Li J, Lim MS, Li S, Brock M, Pique ME, Woods VL, Jr., et al. 2008. Vibrio cholerae toxin-coregulated pilus structure analyzed by hydrogen/deuterium exchange mass spectrometry. Structure 16: 137-148. https://doi.org/10.1016/j.str.2007.10.027
  12. Iredell JR, Manning PA. 1994. Biotype-specific tcpA genes in Vibrio cholerae. FEMS Microbiol. Lett. 121: 47-54. https://doi.org/10.1111/j.1574-6968.1994.tb07074.x
  13. Chin CS, Sorenson J, Harris JB, Robins WP, Charles RC, Jean-Charles RR, et al. 2011. The origin of the Haitian cholera outbreak strain. N. Engl. J. Med. 364: 33-42. https://doi.org/10.1056/NEJMoa1012928
  14. Ghosh P, Naha A, Basak S, Ghosh S, Ramamurthy T, Koley H, et al. 2014. Haitian variant tcpA in Vibrio cholerae O1 El Tor strains in Kolkata, India. J. Clin. Microbiol. 52: 1020-1021. https://doi.org/10.1128/JCM.03042-13
  15. Cheney L, Payne M, Kaur S, Lan R. 2021. Multilevel genome typing describes short- and long-term Vibrio cholerae molecular epidemiology. mSystems 6: e0013421.
  16. Shaikh H, Lynch J, Kim J, Excler JL. 2020. Current and future cholera vaccines. Vaccine 38 Suppl 1: A118-A126. https://doi.org/10.1016/j.vaccine.2019.12.011
  17. Ali M, Emch M, Park JK, Yunus M, Clemens J. 2011. Natural cholera infection-derived immunity in an endemic setting. J. Infect. Dis. 204: 912-918. https://doi.org/10.1093/infdis/jir416
  18. Harris AM, Bhuiyan MS, Chowdhury F, Khan AI, Hossain A, Kendall EA, et al. 2009. Antigen-specific memory B-cell responses to Vibrio cholerae O1 infection in Bangladesh. Infect. Immun. 77: 3850-3856. https://doi.org/10.1128/IAI.00369-09
  19. Charles RC, Nakajima R, Liang L, Jasinskas A, Berger A, Leung DT, et al. 2017. Plasma and mucosal immunoglobulin M, immunoglobulin A, and immunoglobulin G responses to the Vibrio cholerae O1 protein immunome in adults with cholera in Bangladesh. J. Infect. Dis. 216: 125-134. https://doi.org/10.1093/infdis/jix253
  20. Kauffman RC, Bhuiyan TR, Nakajima R, Mayo-Smith LM, Rashu R, Hoq MR, et al. 2016. Single-cell analysis of the plasmablast response to Vibrio cholerae demonstrates expansion of cross-reactive memory B cells. mBio 7: e02021-16.
  21. Lopez AL, Gonzales ML, Aldaba JG, Nair GB. 2014. Killed oral cholera vaccines: history, development and implementation challenges. Ther. Adv. Vaccines. 2: 123-136. https://doi.org/10.1177/2051013614537819
  22. Holmgren J. 2021. An update on cholera immunity and current and future cholera vaccines. Trop. Med. Infect. Dis. 6: 64.
  23. McCarty JM, Lock MD, Hunt KM, Simon JK, Gurwith M. 2018. Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45. Vaccine 36: 833-840. https://doi.org/10.1016/j.vaccine.2017.12.062
  24. Levine MM, Kaper JB, Herrington D, Ketley J, Losonsky G, Tacket CO, et al. 1988. Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. Lancet 2: 467-470.
  25. Aktar A, Rahman MA, Afrin S, Akter A, Uddin T, Yasmin T, et al. 2018. Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh. PLoS Negl. Trop. Dis. 12: e0006399.
  26. Islam K, Hossain M, Kelly M, Mayo Smith LM, Charles RC, Bhuiyan TR, et al. 2018. Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers. PLoS Negl. Trop. Dis. 12: e0006376.
  27. Mayo-Smith LM, Simon JK, Chen WH, Haney D, Lock M, Lyon CE, et al. 2017. The live attenuated cholera vaccine CVD 103-HgR primes responses to the toxin-coregulated pilus antigen TcpA in subjects challenged with wild-type Vibrio cholerae. Clin. Vaccine Immunol. 24: e00470-16.
  28. Rollenhagen JE, Kalsy A, Cerda F, John M, Harris JB, Larocque RC, et al. 2006. Transcutaneous immunization with toxin-coregulated pilin A induces protective immunity against Vibrio cholerae O1 El Tor challenge in mice. Infect. Immun. 74: 5834-5839. https://doi.org/10.1128/IAI.00438-06
  29. Asaduzzaman M, Ryan ET, John M, Hang L, Khan AI, Faruque ASG, et al. 2004. The major subunit of the toxin-coregulated pilus TcpA induces mucosal and systemic immunoglobulin A immune responses in patients with cholera caused by Vibrio cholerae O1 and O139. Infect. Immun. 72: 4448-4454. https://doi.org/10.1128/IAI.72.8.4448-4454.2004
  30. Taylor RK, Kirn TJ, Meeks MD, Wade TK, Wade WF. 2004. A Vibrio cholerae classical TcpA amino acid sequence induces protective antibody that binds an area hypothesized to be important for toxin-coregulated pilus structure. Infect. Immun. 72: 6050-6060. https://doi.org/10.1128/IAI.72.10.6050-6060.2004
  31. Yu RR, DiRita VJ. 2002. Regulation of gene expression in Vibrio cholerae by ToxT involves both antirepression and RNA polymerase stimulation. Mol. Microbiol. 43: 119-134. https://doi.org/10.1046/j.1365-2958.2002.02721.x
  32. Sanchez J, Medina G, Buhse T, Holmgren J, Soberon-Chavez G. 2004. Expression of cholera toxin under non-AKI conditions in Vibrio cholerae El Tor induced by increasing the exposed surface of cultures. J. Bacteriol. 186: 1355-1361. https://doi.org/10.1128/JB.186.5.1355-1361.2004
  33. Cobaxin M, Martinez H, Ayala G, Holmgren J, Sjoling A, Sanchez J. 2014. Cholera toxin expression by El Tor Vibrio cholerae in shallow culture growth conditions. Microb. Pathog. 66: 5-13. https://doi.org/10.1016/j.micpath.2013.11.002
  34. Jonson G, Svennerholm A-M, Holmgren J. 1990. Expression of virulence factors by classical and El Tor Vibrio cholerae in vivo and in vitro. FEMS Microbiol. Lett. 74: 221-228. https://doi.org/10.1111/j.1574-6968.1990.tb04067.x
  35. Iwanaga M, Yamamoto K, Higa N, Ichinose Y, Nakasone N, Tanabe M. 1986. Culture conditions for stimulating cholera toxin production by Vibrio cholerae O1 El Tor. Microbiol. Immunol. 30: 1075-1083. https://doi.org/10.1111/j.1348-0421.1986.tb03037.x
  36. Lee D, Kim EJ, Baek Y, Lee J, Yoon Y, Nair GB, et al. 2020. Alterations in glucose metabolism in Vibrio cholerae serogroup O1 El Tor biotype strains. Sci. Rep. 10: 308.
  37. Baek Y, Lee D, Lee J, Yoon Y, Nair GB, Kim DW, et al. 2020. Cholera toxin production in Vibrio cholerae O1 El Tor biotype strains in single-phase culture. Front. Microbiol. 11: 825.
  38. Kim EJ, Yu HJ, Lee JH, Kim JO, Han SH, Yun CH, et al. 2017. Replication of Vibrio cholerae classical CTX phage. Proc. Natl. Acad. Sci. USA 114: 2343-2348. https://doi.org/10.1073/pnas.1701335114
  39. Legros D, Partners of the Global Task Force on Cholera C. 2018. Global cholera epidemiology: Opportunities to reduce the burden of cholera by 2030. J. Infect. Dis. 218: S137-S140. https://doi.org/10.1093/infdis/jiy486
  40. Harris JB. 2018. Cholera: Immunity and prospects in vaccine development. J. Infect. Dis. 218: S141-S146. https://doi.org/10.1093/infdis/jiy414
  41. Teoh SL, Kotirum S, Hutubessy RCW, Chaiyakunapruk N. 2018. Global economic evaluation of oral cholera vaccine: A systematic review. Hum. vaccin. Immunother. 14: 420-429. https://doi.org/10.1080/21645515.2017.1392422
  42. Hauke CA, Taylor RK. 2017. Production of putative enhanced oral cholera vaccine strains that express toxin-coregulated pilus. PLoS One 12: e0175170.
  43. Zareitaher T, Sadat Ahmadi T, Latif Mousavi Gargari S. 2022. Immunogenic efficacy of DNA and protein-based vaccine from a chimeric gene consisting OmpW, TcpA and CtxB of Vibrio cholerae. Immunobiology 227: 152190.
  44. Sharma MK, Singh NK, Jani D, Sisodia R, Thungapathra M, Gautam JK, et al. 2008. Expression of toxin co-regulated pilus subunit A (TcpA) of Vibrio cholerae and its immunogenic epitopes fused to cholera toxin B subunit in transgenic tomato (Solanum lycopersicum). Plant Cell Rep. 27: 307-318. https://doi.org/10.1007/s00299-007-0464-y
  45. Sit B, Fakoya B, Waldor MK. 2022. Animal models for dissecting Vibrio cholerae intestinal pathogenesis and immunity. Curr. Opin. Microbiol. 65: 1-7. https://doi.org/10.1016/j.mib.2021.09.007
  46. Heidelberg JF, Eisen JA, Nelson WC, Clayton RA, Gwinn ML, Dodson RJ, et al. 2000. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406: 477-483. https://doi.org/10.1038/35020000