전체메뉴
검색
Article Search

JMB Journal of Microbiolog and Biotechnology

QR Code QR Code

Research article

Molecular and Cellular Microbiology (MCM)  |  Microbial Genetics, Physiology, and Metabolism

Variations in the Antivirulence Effects of Fatty Acids and Virstatin against Vibrio cholerae Strains

Donghyun Lee1,2 †, Jayun Joo1,2 †, Hunseok Choi1,2, Seonghyeon Son1,2, Jonghyun Bae1,2, Dong Wook Kim1,2*, and Eun Jin Kim1,2*

1Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan 15588, Republic of Korea
2Institute of Pharmacological Research, Hanyang University, Ansan 15588, Republic of Korea

Correspondence to:
Dong Wook Kim,         dongwook@hanyang.ac.kr

†These authors contributed equally to this work.
Received: May 7, 2024; Revised: June 27, 2024; Accepted: June 28, 2024

J. Microbiol. Biotechnol. 2024; 34(9): 1757-1768

Published September 28, 2024 https://doi.org/10.4014/jmb.2405.05002

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

The expression of two major virulence factors of Vibrio cholerae, cholera toxin (CT) and toxin co-regulated pilus (TCP), is induced by environmental stimuli through a cascade of interactions among regulatory proteins known as the ToxR regulon when the bacteria reach the human small intestine. ToxT is produced via the ToxR regulon and acts as the direct transcriptional activator of CT (ctxAB), TCP (tcp gene cluster), and other virulence genes. Unsaturated fatty acids (UFAs) and several small-molecule inhibitors of ToxT have been developed as antivirulence agents against V. cholerae. This study reports the inhibitory effects of fatty acids and virstatin (a small-molecule inhibitor of ToxT) on the transcriptional activation functions of ToxT in isogenic derivatives of V. cholerae strains containing various toxT alleles. The fatty acids and virstatin had discrete effects depending on the ToxT allele (different by 2 amino acids), V. cholerae strain, and culture conditions, indicating that V. cholerae strains could overcome the effects of UFAs and small-molecule inhibitors by acquiring point mutations in toxT. Our results suggest that small-molecule inhibitors should be examined thoroughly against various V. cholerae strains and toxT alleles during development.

Keywords

Cholera, Vibrio cholerae, cholera toxin (CT), toxin co-regulated pilus (TCP), ToxT, fatty acid, virstatin

Graphical Abstract


References

  1. Kanungo S, Azman AS, Ramamurthy T, Deen J, Dutta S. 2022. Cholera. Lancet 399: 1429-1440.
    Pubmed
  2. Clemens JD, Nair GB, Ahmed T, Qadri F, Holmgren J. 2017. Cholera. Lancet 390: 1539-1549.
    Pubmed
  3. Kaper JB, Morris JG, Jr., Levine MM. 1995. Cholera. Clin. Microbiol. Rev. 8: 48-86.
    Pubmed PMC
  4. Safa A, Nair GB, Kong RY. 2010. Evolution of new variants of Vibrio cholerae O1. Trends Microbiol. 18: 46-54.
    Pubmed
  5. 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.
    Pubmed PMC
  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.
    Pubmed
  7. Nair GB, Qadri F, Holmgren J, Svennerholm AM, Safa A, Bhuiyan NA, et al. 2006. Cholera due to altered El Tor strains of Vibrio cholerae O1 in Bangladesh. J. Clin. Microbiol. 44: 4211-4213.
    Pubmed PMC
  8. Nguyen BM, Lee JH, Cuong NT, Choi SY, Hien NT, Anh DD, et al. 2009. Cholera outbreaks caused by an altered Vibrio cholerae O1 El Tor biotype strain producing classical cholera toxin B in Vietnam in 2007 to 2008. J. Clin. Microbiol. 47: 1568-1571.
    Pubmed PMC
  9. Childers BM, Klose KE. 2007. Regulation of virulence in Vibrio cholerae: the ToxR regulon. Future Microbiol. 2: 335-344.
    Pubmed
  10. Hsiao A, Zhu J. 2020. Pathogenicity and virulence regulation of Vibrio cholerae at the interface of host-gut microbiome interactions. Virulence. 11: 1582-1599.
    Pubmed PMC
  11. Li J, Lim MS, Li S, Brock M, Pique ME, Woods VL, Jr., Craig L. 2008. Vibrio cholerae toxin-coregulated pilus structure analyzed by hydrogen/deuterium exchange mass spectrometry. Structure 16: 137-148.
    Pubmed PMC
  12. Waldor MK, Mekalanos JJ. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272: 1910-1914.
    Pubmed
  13. DiRita VJ, Neely M, Taylor RK, Bruss PM. 1996. Differential expression of the ToxR regulon in classical and E1 Tor biotypes of Vibrio cholerae is due to biotype-specific control over toxT expression. Proc. Natl. Acad. Sci. USA 93: 7991-7995.
    Pubmed PMC
  14. Naha A, Withey JH, Mukherjee P, Saha RN, Samanta P, Ghosh A, et al. 2022. Elucidating the correlation between the number of TTTTGAT heptamer repeats and cholera toxin promoter activity in Vibrio cholerae O1 pandemic strains. FEMS Microbiol. Lett. 369: fnac041.
    Pubmed
  15. 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.
    Pubmed
  16. Miller VL, Mekalanos JJ. 1984. Synthesis of cholera toxin is positively regulated at the transcriptional level by toxR. Proc. Natl. Acad. Sci. USA 81: 3471-3475.
    Pubmed PMC
  17. Withey JH, DiRita VJ. 2006. The toxbox: specific DNA sequence requirements for activation of Vibrio cholerae virulence genes by ToxT. Mol. Microbiol. 59: 1779-1789.
    Pubmed
  18. Waldor MK, Tschape H, Mekalanos JJ. 1996. A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. J. Bacteriol. 178: 4157-4165.
    Pubmed PMC
  19. 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.
    Pubmed PMC
  20. 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.
    Pubmed
  21. Baek Y, Lee D, Lee J, Yoon Y, Nair GB, Kim DW, Kim EJ. 2020. Cholera toxin production in Vibrio cholerae O1 El Tor biotype strains in single-phase culture. Front. Microbiol. 11: 825.
    Pubmed PMC
  22. Lee D, Choi H, Son S, Bae J, Joo J, Kim DW, Kim EJ. 2023. Expression of cholera toxin (CT) and the toxin co-regulated pilus (TCP) by variants of ToxT in Vibrio cholerae strains. Toxins (Basel) 15: 507.
    Pubmed PMC
  23. Choi H, Son S, Lee D, Bae J, Seo E, Kim DW, Kim EJ. 2023. Intracellular expression of CTB in Vibrio cholerae strains in laboratory culture conditions. J. Microbiol. Biotechnol. 33: 736-744.
    Pubmed PMC
  24. Kim EJ, Bae J, Ju YJ, Ju D-B, Lee D, Son S, et al. 2022. Inactivated Vibrio cholerae strains that express TcpA via the toxT-139F allele induce antibody responses against TcpA. J. Microbiol. Biotechnol. 32: 1396-1405.
    Pubmed PMC
  25. Hung DT, Shakhnovich EA, Pierson E, Mekalanos JJ. 2005. Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 310: 670-674.
    Pubmed
  26. Anthouard R, DiRita VJ. 2013. Small-molecule inhibitors of toxT expression in Vibrio cholerae. mBio 4: e00403-13.
    Pubmed PMC
  27. Woodbrey AK, Onyango EO, Pellegrini M, Kovacikova G, Taylor RK, Gribble GW, Kull FJ. 2017. A new class of inhibitors of the AraC family virulence regulator Vibrio cholerae ToxT. Sci. Rep. 7: 45011.
    Pubmed PMC
  28. Chatterjee A, Dutta PK, Chowdhury R. 2007. Effect of fatty acids and cholesterol present in bile on expression of virulence factors and motility of Vibrio cholerae. Infect. Immun. 75: 1946-1953.
    Pubmed PMC
  29. Withey JH, Nag D, Plecha SC, Sinha R, Koley H. 2015. Conjugated linoleic acid reduces cholera toxin production in vitro and in vivo by inhibiting Vibrio cholerae ToxT activity. Antimicrob. Agents Chemother. 59: 7471-7476.
    Pubmed PMC
  30. Lowden MJ, Skorupski K, Pellegrini M, Chiorazzo MG, Taylor RK, Kull FJ. 2010. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes. Proc. Natl. Acad. Sci. USA 107: 2860-2865.
    Pubmed PMC
  31. Shakhnovich EA, Hung DT, Pierson E, Lee K, Mekalanos JJ. 2007. Virstatin inhibits dimerization of the transcriptional activator ToxT. Proc. Natl. Acad. Sci. USA 104: 2372-2377.
    Pubmed PMC
  32. Cruite JT, Kovacikova G, Clark KA, Woodbrey AK, Skorupski K, Kull FJ. 2019. Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile. Commun. Biol. 2: 440.
    Pubmed PMC
  33. Kim EJ, Lee D, Moon SH, Lee CH, Kim SJ, Lee JH, et al. 2014. Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants. PLoS Pathog. 10: e1004384.
    Pubmed PMC
  34. 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.
    Pubmed PMC
  35. Plecha SC, Withey JH. 2015. Mechanism for inhibition of Vibrio cholerae ToxT activity by the unsaturated fatty acid components of bile. J. Bacteriol. 197: 1716-1725.
    Pubmed PMC
  36. Lagos R, Avendano A, Prado V, Horwitz I, Wasserman S, Losonsky G, et al. 1995. Attenuated live cholera vaccine strain CVD 103HgR elicits significantly higher serum vibriocidal antibody titers in persons of blood group O. Infect. Immun. 63: 707-709.
    Pubmed PMC
  37. 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.
    Pubmed PMC
  38. 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.
    Pubmed PMC
  39. Satchell KJ, Jones CJ, Wong J, Queen J, Agarwal S, Yildiz FH. 2016. Phenotypic analysis reveals that the 2010 Haiti cholera epidemic is linked to a hypervirulent strain. Infect. Immun. 84: 2473-2481.
    Pubmed PMC
  40. 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.
  41. D'Mello-Guyett L, Gallandat K, Van den Bergh R, Taylor D, Bulit G, Legros D, et al. 2020. Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: a scoping review of current international guidelines. PLoS One 15: e0226549.
    Pubmed PMC
  42. Shaikh H, Lynch J, Kim J, Excler JL. 2020. Current and future cholera vaccines. Vaccine 38 Suppl. 1: A118-A126.
    Pubmed
  43. Sit B, Fakoya B, Waldor MK. 2022. Emerging concepts in cholera vaccine design. Ann. Rev. Microbiol. 76: 681-702.
    Pubmed
  44. Chowdhury F, Ali Syed K, Akter A, Rahman Bhuiyan T, Tauheed I, Khaton F, et al. 2021. A phase I/II study to evaluate safety, tolerability and immunogenicity of Hillchol(R), an inactivated single Hikojima strain based oral cholera vaccine, in a sequentially age descending population in Bangladesh. Vaccine 39: 4450-4457.
    Pubmed
  45. Clatworthy AE, Pierson E, Hung DT. 2007. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol. 3: 541548.
    Pubmed
  46. Sarveswari HB, Gupta KK, Durai R, Solomon AP. 2023. Development of a smart pH-responsive nano-polymer drug, 2-methoxy-4vinylphenol conjugate against the intestinal pathogen, Vibrio cholerae. Sci. Rep. 13: 1250.
    Pubmed PMC
  47. Childers BM, Cao X, Weber GG, Demeler B, Hart PJ, Klose KE. 2011. N-terminal residues of the Vibrio cholerae virulence regulatory protein ToxT involved in dimerization and modulation by fatty acids. J. Biol. Chem. 286: 28644-28655.
    Pubmed PMC
  48. 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.
    Pubmed PMC
  49. 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.
    Pubmed PMC
  50. Faruque SM, Tam VC, Chowdhury N, Diraphat P, Dziejman M, Heidelberg JF, et al. 2007. Genomic analysis of the Mozambique strain of Vibrio cholerae O1 reveals the origin of El Tor strains carrying classical CTX prophage. Proc. Natl. Acad. Sci. USA104: 5151- 5156.
    Pubmed PMC

Related articles in JMB

More Related Articles

Article

Research article

J. Microbiol. Biotechnol. 2024; 34(9): 1757-1768

Published online September 28, 2024 https://doi.org/10.4014/jmb.2405.05002

Copyright © The Korean Society for Microbiology and Biotechnology.

Variations in the Antivirulence Effects of Fatty Acids and Virstatin against Vibrio cholerae Strains

Donghyun Lee1,2 †, Jayun Joo1,2 †, Hunseok Choi1,2, Seonghyeon Son1,2, Jonghyun Bae1,2, Dong Wook Kim1,2*, and Eun Jin Kim1,2*

1Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan 15588, Republic of Korea
2Institute of Pharmacological Research, Hanyang University, Ansan 15588, Republic of Korea

Correspondence to:Dong Wook Kim,         dongwook@hanyang.ac.kr

†These authors contributed equally to this work.

Received: May 7, 2024; Revised: June 27, 2024; Accepted: June 28, 2024

Abstract

The expression of two major virulence factors of Vibrio cholerae, cholera toxin (CT) and toxin co-regulated pilus (TCP), is induced by environmental stimuli through a cascade of interactions among regulatory proteins known as the ToxR regulon when the bacteria reach the human small intestine. ToxT is produced via the ToxR regulon and acts as the direct transcriptional activator of CT (ctxAB), TCP (tcp gene cluster), and other virulence genes. Unsaturated fatty acids (UFAs) and several small-molecule inhibitors of ToxT have been developed as antivirulence agents against V. cholerae. This study reports the inhibitory effects of fatty acids and virstatin (a small-molecule inhibitor of ToxT) on the transcriptional activation functions of ToxT in isogenic derivatives of V. cholerae strains containing various toxT alleles. The fatty acids and virstatin had discrete effects depending on the ToxT allele (different by 2 amino acids), V. cholerae strain, and culture conditions, indicating that V. cholerae strains could overcome the effects of UFAs and small-molecule inhibitors by acquiring point mutations in toxT. Our results suggest that small-molecule inhibitors should be examined thoroughly against various V. cholerae strains and toxT alleles during development.

Keywords: Cholera, Vibrio cholerae, cholera toxin (CT), toxin co-regulated pilus (TCP), ToxT, fatty acid, virstatin

References

  1. Kanungo S, Azman AS, Ramamurthy T, Deen J, Dutta S. 2022. Cholera. Lancet 399: 1429-1440.
    Pubmed
  2. Clemens JD, Nair GB, Ahmed T, Qadri F, Holmgren J. 2017. Cholera. Lancet 390: 1539-1549.
    Pubmed
  3. Kaper JB, Morris JG, Jr., Levine MM. 1995. Cholera. Clin. Microbiol. Rev. 8: 48-86.
    Pubmed KoreaMed
  4. Safa A, Nair GB, Kong RY. 2010. Evolution of new variants of Vibrio cholerae O1. Trends Microbiol. 18: 46-54.
    Pubmed
  5. 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.
    Pubmed KoreaMed
  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.
    Pubmed
  7. Nair GB, Qadri F, Holmgren J, Svennerholm AM, Safa A, Bhuiyan NA, et al. 2006. Cholera due to altered El Tor strains of Vibrio cholerae O1 in Bangladesh. J. Clin. Microbiol. 44: 4211-4213.
    Pubmed KoreaMed
  8. Nguyen BM, Lee JH, Cuong NT, Choi SY, Hien NT, Anh DD, et al. 2009. Cholera outbreaks caused by an altered Vibrio cholerae O1 El Tor biotype strain producing classical cholera toxin B in Vietnam in 2007 to 2008. J. Clin. Microbiol. 47: 1568-1571.
    Pubmed KoreaMed
  9. Childers BM, Klose KE. 2007. Regulation of virulence in Vibrio cholerae: the ToxR regulon. Future Microbiol. 2: 335-344.
    Pubmed
  10. Hsiao A, Zhu J. 2020. Pathogenicity and virulence regulation of Vibrio cholerae at the interface of host-gut microbiome interactions. Virulence. 11: 1582-1599.
    Pubmed KoreaMed
  11. Li J, Lim MS, Li S, Brock M, Pique ME, Woods VL, Jr., Craig L. 2008. Vibrio cholerae toxin-coregulated pilus structure analyzed by hydrogen/deuterium exchange mass spectrometry. Structure 16: 137-148.
    Pubmed KoreaMed
  12. Waldor MK, Mekalanos JJ. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272: 1910-1914.
    Pubmed
  13. DiRita VJ, Neely M, Taylor RK, Bruss PM. 1996. Differential expression of the ToxR regulon in classical and E1 Tor biotypes of Vibrio cholerae is due to biotype-specific control over toxT expression. Proc. Natl. Acad. Sci. USA 93: 7991-7995.
    Pubmed KoreaMed
  14. Naha A, Withey JH, Mukherjee P, Saha RN, Samanta P, Ghosh A, et al. 2022. Elucidating the correlation between the number of TTTTGAT heptamer repeats and cholera toxin promoter activity in Vibrio cholerae O1 pandemic strains. FEMS Microbiol. Lett. 369: fnac041.
    Pubmed
  15. 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.
    Pubmed
  16. Miller VL, Mekalanos JJ. 1984. Synthesis of cholera toxin is positively regulated at the transcriptional level by toxR. Proc. Natl. Acad. Sci. USA 81: 3471-3475.
    Pubmed KoreaMed
  17. Withey JH, DiRita VJ. 2006. The toxbox: specific DNA sequence requirements for activation of Vibrio cholerae virulence genes by ToxT. Mol. Microbiol. 59: 1779-1789.
    Pubmed
  18. Waldor MK, Tschape H, Mekalanos JJ. 1996. A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. J. Bacteriol. 178: 4157-4165.
    Pubmed KoreaMed
  19. 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.
    Pubmed KoreaMed
  20. 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.
    Pubmed
  21. Baek Y, Lee D, Lee J, Yoon Y, Nair GB, Kim DW, Kim EJ. 2020. Cholera toxin production in Vibrio cholerae O1 El Tor biotype strains in single-phase culture. Front. Microbiol. 11: 825.
    Pubmed KoreaMed
  22. Lee D, Choi H, Son S, Bae J, Joo J, Kim DW, Kim EJ. 2023. Expression of cholera toxin (CT) and the toxin co-regulated pilus (TCP) by variants of ToxT in Vibrio cholerae strains. Toxins (Basel) 15: 507.
    Pubmed KoreaMed
  23. Choi H, Son S, Lee D, Bae J, Seo E, Kim DW, Kim EJ. 2023. Intracellular expression of CTB in Vibrio cholerae strains in laboratory culture conditions. J. Microbiol. Biotechnol. 33: 736-744.
    Pubmed KoreaMed
  24. Kim EJ, Bae J, Ju YJ, Ju D-B, Lee D, Son S, et al. 2022. Inactivated Vibrio cholerae strains that express TcpA via the toxT-139F allele induce antibody responses against TcpA. J. Microbiol. Biotechnol. 32: 1396-1405.
    Pubmed KoreaMed
  25. Hung DT, Shakhnovich EA, Pierson E, Mekalanos JJ. 2005. Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 310: 670-674.
    Pubmed
  26. Anthouard R, DiRita VJ. 2013. Small-molecule inhibitors of toxT expression in Vibrio cholerae. mBio 4: e00403-13.
    Pubmed KoreaMed
  27. Woodbrey AK, Onyango EO, Pellegrini M, Kovacikova G, Taylor RK, Gribble GW, Kull FJ. 2017. A new class of inhibitors of the AraC family virulence regulator Vibrio cholerae ToxT. Sci. Rep. 7: 45011.
    Pubmed KoreaMed
  28. Chatterjee A, Dutta PK, Chowdhury R. 2007. Effect of fatty acids and cholesterol present in bile on expression of virulence factors and motility of Vibrio cholerae. Infect. Immun. 75: 1946-1953.
    Pubmed KoreaMed
  29. Withey JH, Nag D, Plecha SC, Sinha R, Koley H. 2015. Conjugated linoleic acid reduces cholera toxin production in vitro and in vivo by inhibiting Vibrio cholerae ToxT activity. Antimicrob. Agents Chemother. 59: 7471-7476.
    Pubmed KoreaMed
  30. Lowden MJ, Skorupski K, Pellegrini M, Chiorazzo MG, Taylor RK, Kull FJ. 2010. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes. Proc. Natl. Acad. Sci. USA 107: 2860-2865.
    Pubmed KoreaMed
  31. Shakhnovich EA, Hung DT, Pierson E, Lee K, Mekalanos JJ. 2007. Virstatin inhibits dimerization of the transcriptional activator ToxT. Proc. Natl. Acad. Sci. USA 104: 2372-2377.
    Pubmed KoreaMed
  32. Cruite JT, Kovacikova G, Clark KA, Woodbrey AK, Skorupski K, Kull FJ. 2019. Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile. Commun. Biol. 2: 440.
    Pubmed KoreaMed
  33. Kim EJ, Lee D, Moon SH, Lee CH, Kim SJ, Lee JH, et al. 2014. Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants. PLoS Pathog. 10: e1004384.
    Pubmed KoreaMed
  34. 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.
    Pubmed KoreaMed
  35. Plecha SC, Withey JH. 2015. Mechanism for inhibition of Vibrio cholerae ToxT activity by the unsaturated fatty acid components of bile. J. Bacteriol. 197: 1716-1725.
    Pubmed KoreaMed
  36. Lagos R, Avendano A, Prado V, Horwitz I, Wasserman S, Losonsky G, et al. 1995. Attenuated live cholera vaccine strain CVD 103HgR elicits significantly higher serum vibriocidal antibody titers in persons of blood group O. Infect. Immun. 63: 707-709.
    Pubmed KoreaMed
  37. 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.
    Pubmed KoreaMed
  38. 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.
    Pubmed KoreaMed
  39. Satchell KJ, Jones CJ, Wong J, Queen J, Agarwal S, Yildiz FH. 2016. Phenotypic analysis reveals that the 2010 Haiti cholera epidemic is linked to a hypervirulent strain. Infect. Immun. 84: 2473-2481.
    Pubmed KoreaMed
  40. 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.
  41. D'Mello-Guyett L, Gallandat K, Van den Bergh R, Taylor D, Bulit G, Legros D, et al. 2020. Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: a scoping review of current international guidelines. PLoS One 15: e0226549.
    Pubmed KoreaMed
  42. Shaikh H, Lynch J, Kim J, Excler JL. 2020. Current and future cholera vaccines. Vaccine 38 Suppl. 1: A118-A126.
    Pubmed
  43. Sit B, Fakoya B, Waldor MK. 2022. Emerging concepts in cholera vaccine design. Ann. Rev. Microbiol. 76: 681-702.
    Pubmed
  44. Chowdhury F, Ali Syed K, Akter A, Rahman Bhuiyan T, Tauheed I, Khaton F, et al. 2021. A phase I/II study to evaluate safety, tolerability and immunogenicity of Hillchol(R), an inactivated single Hikojima strain based oral cholera vaccine, in a sequentially age descending population in Bangladesh. Vaccine 39: 4450-4457.
    Pubmed
  45. Clatworthy AE, Pierson E, Hung DT. 2007. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol. 3: 541548.
    Pubmed
  46. Sarveswari HB, Gupta KK, Durai R, Solomon AP. 2023. Development of a smart pH-responsive nano-polymer drug, 2-methoxy-4vinylphenol conjugate against the intestinal pathogen, Vibrio cholerae. Sci. Rep. 13: 1250.
    Pubmed KoreaMed
  47. Childers BM, Cao X, Weber GG, Demeler B, Hart PJ, Klose KE. 2011. N-terminal residues of the Vibrio cholerae virulence regulatory protein ToxT involved in dimerization and modulation by fatty acids. J. Biol. Chem. 286: 28644-28655.
    Pubmed KoreaMed
  48. 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.
    Pubmed KoreaMed
  49. 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.
    Pubmed KoreaMed
  50. Faruque SM, Tam VC, Chowdhury N, Diraphat P, Dziejman M, Heidelberg JF, et al. 2007. Genomic analysis of the Mozambique strain of Vibrio cholerae O1 reveals the origin of El Tor strains carrying classical CTX prophage. Proc. Natl. Acad. Sci. USA104: 5151- 5156.
    Pubmed KoreaMed