Chlamydia trachomatis infection co-operatively enhances HPV E6-E7 oncogenes mediated tumorigenesis and immunosuppression

Naveen Challagundla, Jean Chrisophe-Bourdon, Reena Agrawal-Rajput (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Chlamydia trachomatis and human papilloma virus (HPV) are the two most common sexually transmitted infections among women. HPV infection can increase the risk of cervical cancer and infertility while C. trachomatis induces pelvic inflammatory disease. Here, we elucidate the molecular conundrum of the co-infection of HPV and C. trachomatis infection and their outcome with respect to cervical cancer. HPV infection was mimicked by overexpression of HPV 16 E6-E7 or using human cervical cell lines SiHa and C33a (with and without HPV 16 respectively). HPV transfected co-infection increased cell proliferation and resistance to H202 and TNFα-induced cell death compared to individual infections. These changes are brought by alteration in the cell cycle proteins (CDK2, CDK6 and Bcl2) and thus increasing the stemness of the epithelial cells as observed by increased colony forming units and CD133 expression. The co-infection also induces change in the mRNA levels of cells which are involved in mesenchymal phenotype. C. trachomatis in presence of E6-E7 overexpression caused cervical epithelial neoplasm in mice with increased Ki67 expression and decreased P53 levels. Stem cell marker, CD133 expression also increased in the cervical tissues of both infected and co-infected group of mice. The cells obtained from the cervix were able to grow continuously in ex vivo cultures. All these results indicate the co-existence of the C. trachomatis and HPV 16 might increase the risk of cervical cancer.

Original languageEnglish
Article number105929
Number of pages11
JournalMicrobial Pathogenesis
Volume175
Early online date22 Dec 2022
DOIs
Publication statusPublished - Feb 2023

Keywords

  • Apoptosis
  • C. trachomatis
  • Cellular transformation
  • Cervical cancer
  • E6-E7

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology

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