A systemic network for Chlamydia pneumoniae entry into human cells.
Bacterial entry is a multistep process triggering a complex network, yet the molecular complexity of this network remains largely unsolved. By employing a systems biology approach, we reveal a systemic bacterial-entry network initiated by Chlamydia pneumoniae, a widespread opportunistic pathogen. The network consists of nine functional modules (i.e., groups of proteins) associated with various cellular functions, including receptor systems, cell adhesion, transcription, and endocytosis. The peak levels of gene expression for these modules change rapidly during C. pneumoniae entry, with cell adhesion occurring at 5 min postinfection, receptor and actin activity at 25 min, and endocytosis at 2 h. A total of six membrane proteins (chemokine C-X-C motif receptor 7 [CXCR7], integrin beta 2 [ITGB2], platelet-derived growth factor beta polypeptide [PDGFB], vascular endothelial growth factor [VEGF], vascular cell adhesion molecule 1 [VCAM1], and GTP binding protein overexpressed in skeletal muscle [GEM]) play a key role during C. pneumoniae entry, but none alone is essential to prevent entry. The combination knockdown of three genes (coding for CXCR7, ITGB2, and PDGFB) significantly inhibits C. pneumoniae entry, but the entire network is resistant to the six-gene depletion, indicating a resilient network. Our results reveal a complex network for C. pneumoniae entry involving at least six key proteins.
Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA.
Anyou
A
Wang
S Claiborne
SC
Johnston
Joyce
J
Chou
Deborah
D
Dean
D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016993:Chlamydophila pneumoniae / Q000254:growth & development / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D054387:Receptors, CXCR / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D049490:Systems Biology / Q000379:methods*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C501896:ACKR3 protein, human; D018821:CD18 Antigens; D020574:Proto-Oncogene Proteins c-sis; D054387:Receptors, CXCR; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D020559:Monomeric GTP-Binding Proteins