2021
DOI: 10.1101/2021.04.15.439996
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Chlamydia coinfection inhibits HPV-induced safeguards of the cellular and genomic integrity in patient-derived ectocervical organoids

Abstract: Cervical mucosa is continually confronted by coinfections with pathogenic microbes. In addition to human papillomavirus, coinfections with Chlamydia trachomatis have been associated with an increased risk of cervical cancer. However, the dynamics of coinfections, their impact on the epithelia, and their contribution to pathogenesis remain obscure. Using a novel human ectocervical squamous stratified epithelial organoids, we recapitulated the natural infections of the cervix by Chlamydia, HPV, and their coinfec… Show more

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Cited by 4 publications
(7 citation statements)
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“…226,236,237 Furthermore, CT suppresses DNA repair activity by recruiting DDR proteins like Ataxia-telangiectasia-mutated (ATM) away from sites of DSBs. 238 ROS production also causes oxidative DSBs and senescenceassociated heterochromatin foci by subverting the host histones in CT infection. 228 Free radicals damage the DNA and DNA repair factors, and prevent apoptosis resulting in genetic fragility.…”
Section: Hpv/ct Co-infection and Genome Instabilitymentioning
confidence: 99%
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“…226,236,237 Furthermore, CT suppresses DNA repair activity by recruiting DDR proteins like Ataxia-telangiectasia-mutated (ATM) away from sites of DSBs. 238 ROS production also causes oxidative DSBs and senescenceassociated heterochromatin foci by subverting the host histones in CT infection. 228 Free radicals damage the DNA and DNA repair factors, and prevent apoptosis resulting in genetic fragility.…”
Section: Hpv/ct Co-infection and Genome Instabilitymentioning
confidence: 99%
“…Both CT infection and HPV/CT co‐infection trigger the oncogenic MAPK pathway (Ras‐Raf‐MEK‐ERK) that regulates diverse cellular functions including cell proliferation, survival, differentiation, and migration, thus promoting cancer cell growth 243,244 . CT was also reported to activate PI3K/AKT that enhances cellular proliferation, and blocks cell apoptosis 238 . Additionally, CT manipulates intrinsic apoptotic pathways by degrading the MDM2 protein and inducing expression of antiapoptotic proteins like Mcl‐1 234 .…”
Section: Microbiome and Hpvmentioning
confidence: 99%
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“…Chlamydia obstructs HPV-induced processes, such as mismatch repair (MMR), that maintain cellular and genomic integrity in coinfections. During coinfections, inverse modulation of MMR is distinguished by distinct post-translational proteasomal degradation and E2F-mediated transcriptional regulation [ 40 ].…”
Section: Pathogen Association With Hpvmentioning
confidence: 99%
“…Both pathogens upregulate the immune response mediated by tumor necrosis factor (TNF), while C. trachomatis explicitly induces the inflammatory response mediated by IL-17 and NF-kB signaling. Additionally, oxidative phosphorylation, RNA regulation, RNA processing, and elevated MAPK pathways are all significantly affected by chlamydia [ 40 ].…”
Section: Pathogen Association With Hpvmentioning
confidence: 99%