title: Rottlerin-mediated inhibition of Chlamydia trachomatis growth and uptake of sphingolipids is independent of p38-regulated/activated protein kinase (PRAK).
abstract: We previously found that rottlerin, a plant-derived small molecule compound, profoundly inhibited Chlamydia trachomatis growth and blocked sphingolipid trafficking from host cell Golgi into chlamydial inclusions. Since the p38-regulated/activated protein kinase (PRAK) is a known target of rottlerin and is activated in Chlamydia trachomatis-infected cells, we investigated the potential role of this kinase in rottlerin-mediated anti-chlamydial activity. However, we found that a PRAK-specific inhibitor failed to inhibit chlamydial growth, suggesting that the kinase activity of PRAK may not be required for chlamydial intracellular replication. This conclusion was supported by the observation that chlamydial organisms replicated equally well in mouse embryonic fibroblast cells with or without PRAK. Moreover, neither the PRAK inhibitor nor PRAK deficiency altered host sphingolipid trafficking into chlamydial inclusions. Finally, rottlerin maintained its anti-chlamydial activity in PRAK-deficient cells. Together, these observations have demonstrated that PRAK is not required for either the rottlerin-mediated anti-chlamydial activity or rottlerin inhibition of sphingolipid trafficking, suggesting that rottlerin may achieve its inhibitory role by targeting other host factors.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Li
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D047908:Intracellular Signaling Peptides and Proteins; D013107:Sphingolipids; C111049:MAP-kinase-activated kinase 5; C085746:rottlerin; D017346:Protein Serine-Threonine Kinases