This is a preview and has not been published.

Mesenchymal and stemness transdifferentiation via in-vitro infection of T24 cell line with Klebsiella pneumoniae


  • Romaila Abd-El-Raouf Faculty of Science, Cairo University, Giza 12613, Egypt & Urology and Nephrology Center, Faculty of Medicine, Research Department, Mansoura University, Mansoura, Egypt.
  • Salama A. Ouf Faculty of Science, Cairo University, Giza 12613, Egypt.
  • Maha G. Haggag Microbiology & Immunology Unit, Research Institute of Ophthalmology, Giza, Egypt.
  • Khaled F. El-Yasergy Faculty of Science, Cairo University, Giza 12613, Egypt.
  • Mahmoud M. Zakaria Urology and Nephrology Center, Faculty of Medicine, Research Department, Mansoura University, Mansoura, Egypt.



Bacterial infection, Bladder cancer, Epithelial-mesenchymal transition, K. pneumonia, Stemness transdifferentiation


Klebsiella pneumoniae has been found in the urinary tract of some bladder cancer patients. Bacterial presence within tumor tissue may affect the tumor-microenvironment and consequently influence cancer behavior, development, and treatment response. This study investigated mesenchymal and stemness transdifferentiation of bladder cancer cell line due to environmental stress of K. pneumoniae. Cultures of urothelial bladder cancer cell line (T24) were infected with K. pneumoniae with different multiplicity of infection (MOI) for two and four days. Transdifferentiation-associated features were morphologically assessed.

Moreover, transdifferentiation markers were estimated using Q-PCR and immunohistochemistry. Q-PCR data showed an increase in mesenchymal transdifferentiation traits; vimentin expression was upregulated, and cytokeratin19 expression downregulated significantly (P<0.001) compared with controls, which were emphasized by immunohistochemistry results. Moreover, stemness transdifferentiation markers expression increased significantly (P<0.001). The heterogeneous tumor cell population may be altered by bacterial infection, which improves cancer cells' migration and self-renewal ability. Thus, bacteria may be engaged in cancer progression and metastases.  


Download data is not yet available.


Quintanal-Villalonga A, Taniguchi H, Zhan YA, Hasan MM, Chavan SS, Meng F, et al. Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation. J Hematol Oncol. 2021; 14(1): 170.

Wernecke L, Keckeis S, Reichhart N, Strauß O, Salchow DJ. Epithelial-Mesenchymal Transdifferentiation in Pediatric Lens Epithelial Cells. Invest Ophthalmol Vis Sci. 2018;59(15):5785-94.

Arima Y, Nobusue H, Saya H. Targeting of cancer stem cells by differentiation therapy. Cancer Sci. 2020; 111(8): 2689-95.

Yu X, Li M, Guo C, Wu Y, Zhao L, Shi Q, et al. Therapeutic Targeting of Cancer: Epigenetic Homeostasis. Front Oncol. 2021;11.

Dudas J, Ladanyi A, Ingruber J, Steinbichler TB, Riechelmann H. Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance. Cells. 2020; 9(2): 428.

Abdulkareem A, Shelton R, Landini G, Cooper P, Milward M. Periodontal pathogens promote epithelial-mesenchymal transition in oral squamous carcinoma cells in vitro. Cell Adh Migr. 2018; 12(2): 127-37.

Jiang X, Liang L, Chen G, Liu C. Modulation of Immune Components on Stem Cell and Dormancy in Cancer. Cells. 2021; 10(11): 2826.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. Ca-Cancer J Clin. 2020; 70(1): 7-30.

Bergers G, Fendt S-M. The metabolism of cancer cells during metastasis. Nat Rev Cancer. 2021; 21(3): 162-80.

Akhtar S, Al-Shammari A, Al-Abkal J. Chronic urinary tract infection and bladder carcinoma risk: a meta-analysis of case-control and cohort studies. World J Urol. 2018; 36(6): 839-48.

Murray BO, Flores C, Williams C, Flusberg DA, Marr EE, Kwiatkowska KM, et al. Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems. Front Cell Infect Microbiol. 2021; 11.

El Shobaky A, Abbas M, Raouf R, Zakaria MM, Ali-El-Dein B. Effect of pathogenic bacteria on reliability of CK-19, CK-20 and UPII as bladder cancer genetic markers: A molecular biology study. Egypt J Basic Appl Sci. 2015; 2(3): 176-82.

Mustafa M. Prevalence of Quinolones Resistance Proteins Encoding Genes (qnr genes) and Co-Resistance with β-lactams among Klebsiella pneumoniae Isolates from Iraqi Patients. Baghdad Sci J. 2020; 17(2): 0406.

Mustafa MS, Abdullah RM. Detection of 16S rRNA methylases and co-resistance with β-lactams among Klebsiella pneumoniae isolates from Iraqi patients. Baghdad Sci J. 2019; 16(3): 580-7.

Abd-El-Raouf R, Ouf SA, Gabr MM, Zakaria MM, El-Yasergy KF, Ali-El-Dein B. Escherichia coli foster bladder cancer cell line progression via epithelial mesenchymal transition, stemness and metabolic reprogramming. Sci Rep. 2020; 10(1): 18024.

Song S, Vuai MS, Zhong M. The role of bacteria in cancer therapy - enemies in the past, but allies at present. Infect Agent Cancer. 2018; 13: 9.

Fu A, Yao B, Dong T, Chen Y, Yao J, Liu Y, et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell. 2022; 185(8): 1356-72. e26.

Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A. The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health. Front Immunol. 2020; 11.

Leone L, Mazzetta F, Martinelli D, Valente S, Alimandi M, Raffa S, et al. Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells. PloS one. 2016; 11(1): e0146365-e.

Vaidya M, Dmello C, Mogre S. Utility of Keratins as Biomarkers for Human Oral Precancer and Cancer. Life (Basel). 2022; 12(3): 343.

Saha SK, Kim K, Yang G-M, Choi HY, Cho S-G. Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells. Int J Mol Sci. 2018; 19(5): 1423.

Kuburich NA, den Hollander P, Pietz JT, Mani SA. Vimentin and cytokeratin: Good alone, bad together. Seminars in cancer biology. 2021; 12: 006.

Usman S, Waseem NH, Nguyen TKN, Mohsin S, Jamal A, Teh M-T, et al. Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis. Cancers. 2021; 13(19): 4985.

Hofman P, Vouret-Craviari V. Microbes-induced EMT at the crossroad of inflammation and cancer. Gut Microbes. 2012; 3(3): 176-85.

Migita T, Ueda A, Ohishi T, Hatano M, Seimiya H, Horiguchi S-i, et al. Epithelial–mesenchymal transition promotes SOX2 and NANOG expression in bladder cancer. Lab Invest. 2017; 97: 567.

Shi Y, Wang S, Yang R, Wang Z, Zhang W, Liu H, et al. ROS Promote Hypoxia-Induced Keratinocyte Epithelial-Mesenchymal Transition by Inducing SOX2 Expression and Subsequent Activation of Wnt/β-Catenin. Oxid Med Cell Longev. 2022; 2022: 1084006.

Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018; 11(1): 64.

Lim HW, Pak K, Kurabi A, Ryan AF. Lack of the hyaluronan receptor CD44 affects the course of bacterial otitis media and reduces leukocyte recruitment to the middle ear. BMC Immunol. 2019; 20(1): 20.

Rouschop KM, Sylva M, Teske GJ, Hoedemaeker I, Pals ST, Weening JJ, et al. Urothelial CD44 facilitates Escherichia coli infection of the murine urinary tract. J Immunol. 2006; 177(10): 7225-32.

Van der Windt GJ, Florquin S, de Vos AF, van't Veer C, Queiroz KC, Liang J, et al. CD44 deficiency is associated with increased bacterial clearance but enhanced lung inflammation during Gram-negative pneumonia. Am J Pathol. 2010; 177(5): 2483-94.

NOVAK, D., HÜSER, L., ELTON, J. J., UMANSKY, V., ALTEVOGT, P. & UTIKAL, J. 2020. SOX2 in development and cancer biology. Semin Cancer Biol, 67, 74-82.

Md-Akhir MKA, Hussin H, Veerakumarasivam A, Choy CS, Abdullah MA, Abd Ghani F. Immunohistochemical expression of NANOG in urothelial carcinoma of the bladder. Malays J Pathol. 2017; 39(3): 227-34.

Wang Y-J, Herlyn M. The emerging roles of Oct4 in tumor-initiating cells. Am J Physiol Cell Physiol. 2015; 309(11): C709-C18.

Atlasi Y, Mowla SJ, Ziaee SA, Bahrami AR. OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. Int J Cancer. 2007; 120(7): 1598-602.

Abugomaa A, Elbadawy M, Yamawaki H, Usui T, Sasaki K. Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer. Cells. 2020; 9(1): 235-254.

Assadollahi V, Gholami M, Zendedel A, Afsartala Z, Jahanmardi F. Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor. Zahedan J Res Med Sci. 2015; 17(12): e5186.

Sun J. Enteric bacteria and cancer stem cells. Cancers (Basel). 2010; 3(1): 285-97.

Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A. Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection. Cell. 2013; 152(1-2): 51-67.