Chlamydia pneumoniaeGroEL1 Protein Is Cell Surface Associated and Required for Infection of HEp-2 Cells

Abstract

Chlamydia pneumoniae is an important obligate intracellular pathogen that replicates within an inclusion in the eukaryotic cell. The initial event of a chlamydial infection is the adherence to and subsequent uptake of the infectious elementary bodies (EBs) by the human cell. These processes require yet-unidentified bacterial and eukaryotic surface proteins. The GroEL1 protein, which exhibits a very strong antigenicity and in vitro can activate various eukaryotic cells, is a potential pathogenicity factor. We localized the protein during the infection process and found it in the inclusion but outside the chlamydial particles. GroEL1 was also localized on the surface of EBs, and the protein could be washed off the EBs. Latex beads coated with recombinantly produced GroEL1 (rGroEL1) bound in a dose-dependent manner to HEp-2 cells. Likewise, GroEL1, when expressed and displayed on the yeast cell surface, mediated adhesion to HEp-2 cells. Interestingly, the homologous GroEL2 and GroEL3 proteins showed no adhesive properties. Incubation of primary umbilical vein endothelial cells with soluble GroEL1 and GroEL1-coated latex beads activated the translocation of the general transcription factor NF-B into the nucleus. Finally, preincubation of HEp-2 cells with rGroEL1 significantly reduced subsequent infection with C. pneumoniae, although adhesion of infectious bacteria to eukaryotic cells was not affected. Taken together, these data support a role for extracellular GroEL1 in the establishment of the chlamydial infection.

Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells

“…Our study confirmed that following bacterial attachment, typical inclusions formed that were permissive to bacterial growth, resulting in increased infectious progenies in [17][18][19][20][21][22]. Heparin, which forms the majority of GAGs, also plays a critical role in host cells as a receptor for the attachment of the other pathogens such as Bordetella pertussis [35], Hemophilus influenzae [36] or Neisseria gonorrhoeae [37].…”

“…Heparin independent attachment and host invasion has also been described for the C. trachomatis LGV invasive serotype causing a systemic disease, but not for any other serotypes [17][18][19][20][21][22]. This suggests that a heparin-independent attachment mechanism is useful for a pathogen to effectively spread from local lesions, such as the genital tract in this case, to other distinct lymphoid tissue, as observed in pelvic inflammatory disease [42].…”

“…OmcB and GroEL1 molecules [21,22], followed by successful infection. On the other hand, recent work regarding polymorphic membrane proteins (Pmps) interestingly indicated that yeast cells expressing Pmps adhered equally well to GAG-deficient CHO cells and the control CHO K1 cells [41].…”

“…Data from these experiments suggest that heparin, which is the most common GAG, covalently attaches to the core proteins of PG expressed on the host cells and critically functions as a receptor against chlamydial adhesions, such as the outer membrane protein, OmcB [21] or stress protein, GroEL1 [22]. However, the mechanism of C. pneumoniae attachment to lymphocytes remains unknown.…”

Role of Chlamydia in the Development of Ocular Adnexal Lymphoma

“…The discovery that EBs can translocate stored proteins into the host under distinct signaling pathways is further evidence that the entry process results from a dialogue between the bacteria and the host, although many features including EB protein attachment to target cells remain to be clarified or discovered [33,34].…”