title: Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development.
abstract: BACKGROUND
  Chlamydia trachomatis (C. trachomatis) is a clinically significant human pathogen and one of the leading causative agents of sexually transmitted diseases. As obligate intracellular bacteria, C. trachomatis has evolved strategies to redirect the host's signaling and resources for its own survival and propagation. Despite the clinical notoriety of Chlamydia infections, the molecular interactions between C. trachomatis and its host cell proteins remain elusive.
  
  
  RESULTS
  In this study, we focused on the involvement of the host cell epidermal growth factor receptor (EGFR) in C. trachomatis attachment and development. A combination of molecular approaches, pharmacological agents and cell lines were used to demonstrate distinct functional requirements of EGFR in C. trachomatis infection. We show that C. trachomatis increases the phosphorylation of EGFR and of its downstream effectors PLCγ1, Akt and STAT5. While both EGFR and platelet-derived growth factor receptor-β (PDGFRβ) are partially involved in bacterial attachment to the host cell surface, it is only the knockdown of EGFR and not PDGFRβ that affects the formation of C. trachomatis inclusions in the host cells. Inhibition of EGFR results in small immature inclusions, and prevents C. trachomatis-induced intracellular calcium mobilization and the assembly of the characteristic F-actin ring at the inclusion periphery. By using complementary approaches, we demonstrate that the coordinated regulation of both calcium mobilization and F-actin assembly by EGFR are necessary for maturation of chlamydial inclusion within the host cells. A particularly important finding of this study is the co-localization of EGFR with the F-actin at the periphery of C. trachomatis inclusion where it may function to nucleate the assembly of signaling protein complexes for cytoskeletal remodeling required for C. trachomatis development.
  
  
  CONCLUSIONS
  Cumulatively, the data reported here connect the function of EGFR to C. trachomatis attachment and development in the host cells, and this could lead to new venues for targeting C. trachomatis infections and associated diseases.
authors.affiliation: Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. achchhe@gmail.com.
authors.forename: Achchhe L
authors.initials: AL
authors.lastname: Patel
authors.affiliation: Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. xichen@wakehealth.edu.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. scwood@wakehealth.edu.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Wood
authors.affiliation: Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, 01003, USA. esstuart@microbio.umass.edu.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Stuart
authors.affiliation: Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, 01003, USA. karcaro@vasci.umass.edu.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Arcaro
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. dmolina@wakehealth.edu.
authors.forename: Doris P
authors.initials: DP
authors.lastname: Molina
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. snpetro@wakehealth.edu.
authors.forename: Snezana
authors.initials: S
authors.lastname: Petrovic
authors.affiliation: Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. cfurdui@wakehealth.edu.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Furdui
authors.affiliation: Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA. atsang@wakehealth.edu.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Tsang
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation
chemical_list: D066246:ErbB Receptors