Display options
Cite
Sherchand SP, Ibana JA, Zea AH, et al. The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis. PLoS One. 2016;11(9):e0163174doi: 10.1371/journal.pone.0163174.
Sherchand, S. P., Ibana, J. A., Zea, A. H., Quayle, A. J., & Aiyar, A. (2016). The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis. PloS one, 11(9), e0163174. https://doi.org/10.1371/journal.pone.0163174
Sherchand, Shardulendra P, et al. "The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis." PloS one vol. 11,9 (2016): e0163174. doi: https://doi.org/10.1371/journal.pone.0163174
Sherchand SP, Ibana JA, Zea AH, Quayle AJ, Aiyar A. The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis. PLoS One. 2016 Sep 22;11(9):e0163174. doi: 10.1371/journal.pone.0163174. eCollection 2016. PMID: 27658027; PMCID: PMC5033384.
Copy Download .nbib Format: NLM
Share it on

PLoS One. 2016 Sep 22;11(9):e0163174. doi: 10.1371/journal.pone.0163174. eCollection 2016.

The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis.

PloS one

Shardulendra P Sherchand, Joyce A Ibana, Arnold H Zea, Alison J Quayle, Ashok Aiyar

Affiliations

  1. Department of Microbiology, Immunology & Parasitology, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, Louisiana, 70112, United States of America.
  2. Institute of Biology, University of the Philippines, Diliman, Quezon City, Philippines, PH, 1101.

PMID: 27658027 PMCID: PMC5033384 DOI: 10.1371/journal.pone.0163174

Abstract

Chlamydia trachomatis is an obligate intracellular pathogen that requires specific essential nutrients from the host cell, one of which is the amino acid tryptophan. In this context interferon gamma (IFNγ) is the major host protective cytokine against chlamydial infections because it induces the expression of the host enzyme, indoleamine 2,3-dioxygenase 1, that degrades tryptophan, thereby restricting bacterial replication. The mechanism by which IFNγ acts has been dissected in vitro using epithelial cell-lines such as HeLa, HEp-2, or the primary-like endocervical cell-line A2EN. All these cell-lines express the high-risk human papillomavirus oncogenes E6 & E7. While screening cell-lines to identify those suitable for C. trachomatis co-infections with other genital pathogens, we unexpectedly found that tryptophan starvation did not completely block chlamydial development in cell-lines that were HR-HPV negative, such as C33A and 293. Therefore, we tested the hypothesis that HR-HPV oncogenes modulate the effect of tryptophan starvation on chlamydial development by comparing chlamydial development in HeLa and C33A cell-lines that were both derived from cervical carcinomas. Our results indicate that during tryptophan depletion, unlike HeLa, C33A cells generate sufficient intracellular tryptophan via proteasomal activity to permit C. trachomatis replication. By generating stable derivatives of C33A that expressed HPV16 E6, E7 or E6 & E7, we found that E6 expression alone was sufficient to convert C33A cells to behave like HeLa during tryptophan starvation. The reduced tryptophan levels in HeLa cells have a biological consequence; akin to the previously described effect of IFNγ, tryptophan starvation protects C. trachomatis from clearance by doxycycline in HeLa but not C33A cells. Curiously, when compared to the known Homo sapiens proteome, the representation of tryptophan in the HR-HPV E6 & E6AP degradome is substantially lower, possibly providing a mechanism that underlies the lowered intracellular free tryptophan levels in E6-expressing cells during starvation.

Conflict of interest statement

The authors have declared that no competing interests exist.

References

  1. J Infect Dis. 2010 Jun 15;201 Suppl 2:S88-95 - PubMed
  2. Infect Immun. 1994 Sep;62(9):3705-11 - PubMed
  3. Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):9872-7 - PubMed
  4. Am J Pathol. 1938 Sep;14(5):579-93 - PubMed
  5. Infect Agent Cancer. 2016 Aug 16;11:42 - PubMed
  6. Infect Immun. 2007 Nov;75(11):5105-17 - PubMed
  7. PLoS One. 2014 Apr 21;9(4):e95977 - PubMed
  8. Mol Cell. 2012 Oct 26;48(2):242-53 - PubMed
  9. J Clin Invest. 2003 Jun;111(11):1757-69 - PubMed
  10. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998-4002 - PubMed
  11. J Biol Chem. 1964 Jan;239:136-45 - PubMed
  12. Microb Pathog. 2010 Nov;49(5):217-25 - PubMed
  13. J Immunol. 2001 Nov 1;167(9):5420-8 - PubMed
  14. Genitourin Med. 1989 Jan;65(1):22-31 - PubMed
  15. J Clin Microbiol. 1981 Mar;13(3):427-32 - PubMed
  16. Infect Immun. 2000 Apr;68(4):2379-85 - PubMed
  17. J Leukoc Biol. 1989 Jan;45(1):29-34 - PubMed
  18. J Infect Dis. 1975 Jun;131(6):678-87 - PubMed
  19. J Clin Virol. 2007 Dec;40(4):321-4 - PubMed
  20. Biochem J. 1971 Jul;123(4):36P - PubMed
  21. Am J Pathol. 2000 Oct;157(4):1055-62 - PubMed
  22. Infect Immun. 2000 Oct;68(10):6038-40 - PubMed
  23. J Infect Dis. 2000 Sep;182(3):909-16 - PubMed
  24. BMC Infect Dis. 2013 Nov 09;13:531 - PubMed
  25. Virology. 2013 Nov;446(1-2):325-33 - PubMed
  26. Gynecol Oncol. 1984 Sep;19(1):90-7 - PubMed
  27. J BUON. 2014 Oct-Dec;19(4):973-9 - PubMed
  28. Cell Physiol Biochem. 2000;10(1-2):37-55 - PubMed
  29. J Immunol. 2012 Sep 15;189(6):2954-64 - PubMed
  30. Mol Cell Biol. 2008 Mar;28(5):1429-42 - PubMed
  31. Microbiol Rev. 1991 Mar;55(1):143-90 - PubMed
  32. Int J Cancer. 2006 Oct 15;119(8):1878-85 - PubMed
  33. Lab Invest. 1999 Oct;79(10):1299-309 - PubMed
  34. J Gen Microbiol. 1987 Mar;133(3):701-8 - PubMed
  35. Front Microbiol. 2011 Feb 08;2:14 - PubMed
  36. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15971-6 - PubMed
  37. J Pharmacol Exp Ther. 2009 Jul;330(1):359-66 - PubMed
  38. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10658-63 - PubMed
  39. Science. 1998 Oct 23;282(5389):754-9 - PubMed
  40. Mol Microbiol. 2003 Sep;49(5):1347-59 - PubMed
  41. Infect Immun. 2006 Jan;74(1):225-38 - PubMed
  42. J Exp Med. 1953 May;97(5):695-710 - PubMed
  43. Infect Immun. 1999 Apr;67(4):1666-71 - PubMed
  44. Clin Infect Dis. 2015 Nov 15;61(10 ):1573-81 - PubMed
  45. J Interferon Res. 1989 Jun;9(3):329-37 - PubMed
  46. J Virol. 2003 Nov;77(21):11767-80 - PubMed
  47. J Biol Chem. 2014 Jan 10;289(2):1033-48 - PubMed
  48. J Infect Dis. 2010 Dec 15;202(12):1789-99 - PubMed
  49. Infect Immun. 1995 Jan;63(1):199-205 - PubMed
  50. J Cell Sci. 2001 Jan;114(Pt 1):29-36 - PubMed
  51. J Mol Biol. 1968 Dec;38(3):431-5 - PubMed
  52. J Bacteriol. 1968 Dec;96(6):2004-11 - PubMed
  53. J Cell Biol. 2014 Jul 21;206(2):173-82 - PubMed
  54. Med Microbiol Immunol. 2016 Dec;205(6):585-594 - PubMed
  55. J Biol Chem. 2002 Jul 26;277(30):26893-903 - PubMed
  56. Am J Pathol. 1985 Jun;119(3):361-6 - PubMed
  57. FEMS Microbiol Rev. 2005 Nov;29(5):949-59 - PubMed
  58. J Natl Cancer Inst. 1964 Jan;32:135-63 - PubMed
  59. J Biol Chem. 1959 Mar;234(3):592-7 - PubMed
  60. J Reprod Immunol. 2011 Dec;92(1-2):8-20 - PubMed
  61. Sci Rep. 2011;1:150 - PubMed
  62. Br J Cancer. 2012 Jun 26;107(1):53-62 - PubMed
  63. J Clin Microbiol. 1990 Jun;28(6):1098-100 - PubMed
  64. Nat Rev Immunol. 2005 Feb;5(2):149-61 - PubMed
  65. Infect Immun. 2011 Nov;79(11):4425-37 - PubMed
  66. Virology. 2013 Nov;446(1-2):389-96 - PubMed
  67. Front Cell Infect Microbiol. 2014 Jun 03;4:72 - PubMed
  68. J Gen Virol. 1977 Jul;36(1):59-74 - PubMed
  69. J Pharm Pharm Sci. 2000 May-Aug;3(2):268-80 - PubMed
  70. PLoS Pathog. 2014 Jul 31;10(7):e1004286 - PubMed
  71. Infect Dis Obstet Gynecol. 2011;2011:420905 - PubMed
  72. Antimicrob Agents Chemother. 2005 May;49(5):1787-93 - PubMed

Publication Types

Grant support