Chlamydial infection induces pathobiotype-specific protein tyrosine phosphorylation in epithelial cells.
Members of the genus Chlamydia are strict obligate intracellular pathogens that exhibit marked differences in host range and tissue tropism despite sharing a remarkable level of genomic synteny. These pathobiotype differences among chlamydiae are also mirrored in their early interactions with cultured mammalian host cells. Chlamydial attachment and entry is known to trigger protein tyrosine phosphorylation. In this study, we examined the kinetics and pattern of protein tyrosine phosphorylation induced by infection with a comprehensive collection of chlamydial strains exhibiting diversity in host, tissue, and disease tropisms. We report new findings showing that protein tyrosine phosphorylation patterns induced by infection directly correlate with the pathobiotype of the infecting organism. Patterns of protein tyrosine phosphorylation were induced following early infection that unambiguously categorized chlamydial pathobiotypes into four distinct groups: (i) Chlamydia trachomatis trachoma biovars (serovars A to H), (ii) C. trachomatis lymphogranuloma venereum biovars (serovars L1 to L3), (iii) C. muridarum, and (iv) C. pneumoniae and C. caviae. Notably, chlamydia-infected murine and human epithelial cells exhibited the same protein tyrosine phosphorylation patterns; this is indirect evidence suggesting that the phosphorylated protein(s) is of chlamydial origin. If our hypothesis is correct, these heretofore-uncharacterized proteins may represent a novel class of bacterial molecules that influence pathogen-host range or tissue tropism.
Virok
Dezso P
DP
Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, 903 South 4th St., Hamilton, MT 59840, USA.
Nelson
David E
DE
Whitmire
William M
WM
Crane
Deborah D
DD
Goheen
Morgan M
MM
Caldwell
Harlan D
HD
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D002689:Chlamydia / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; C439541:Pmp10 protein, Chlamydia pneumoniae; D011506:Proteins; D014443:Tyrosine