Chlamydia trachomatis-induced alterations in the host cell proteome are required for intracellular growth.
Intracellular pathogens directly alter host cells in order to replicate and survive. While infection-induced changes in host transcription can be readily assessed, posttranscriptional alterations are more difficult to catalog. We applied the global protein stability (GPS) platform, which assesses protein stability based on relative changes in an adjoining fluorescent tag, to identify changes in the host proteome following infection with the obligate intracellular bacteria Chlamydia trachomatis. Our results indicate that C. trachomatis profoundly remodels the host proteome independently of changes in transcription. Additionally, C. trachomatis replication depends on a subset of altered proteins, such as Pin1 and Men1, that regulate the host transcription factor AP-1 controlling host inflammation, stress, and cell survival. Furthermore, AP-1-dependent transcription is activated during infection and required for efficient Chlamydia growth. In summary, this experimental approach revealed that C. trachomatis broadly alters host proteins and can be applied to examine host-pathogen interactions and develop host-based therapeutics.
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Andrew J
AJ
Olive
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Madeleine G
MG
Haff
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02215, USA; Howard Hughes Medical Institute.
Michael J
MJ
Emanuele
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02215, USA; Howard Hughes Medical Institute.
Laura M
LM
Sack
Department of Microbiology and Molecular Genetics, Duke University Medical School, Durham, NC 22710, USA.
Jeffrey R
JR
Barker
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02215, USA; Howard Hughes Medical Institute.
Stephen J
SJ
Elledge
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: starnbach@hms.harvard.edu.
Michael N
MN
Starnbach
D000818:Animals; D002470:Cell Survival; D002690:Chlamydia Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000502:physiology*; D004261:DNA Replication; D005260:Female; D005456:Fluorescent Dyes; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D005456:Fluorescent Dyes; C105373:MEN1 protein, human; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D020543:Proteome; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse