title: Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors.
abstract: Throughout its known history, the gram-negative bacteriumChlamydia pneumoniaehas remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we describe the strategies that have been successfully applied for the identification of nonconventional antichlamydial agents, including target-based and ligand-based virtual screening, ethnopharmacological approach and pharmacophore-based design of antimicrobial peptide-mimicking compounds. Among the antichlamydial agents identified via these strategies, most translational work has been carried out with plant phenolics. Thus, currently available data on their properties as antichlamydial agents are described, highlighting their potential mechanisms of action. In this context, the role of mitogen-activated protein kinase activation in the intracellular growth and survival ofC.pneumoniaeis discussed. Owing to the complex and often complementary pathways applied byC. pneumoniaein the different stages of its life cycle, multitargeted therapy approaches are expected to provide better tools for antichlamydial therapy than agents with a single molecular target.
authors.affiliation: Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland. leena.hanski@helsinki.fi.
authors.forename: Leena
authors.initials: L
authors.lastname: Hanski
authors.affiliation: Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland. pia.vuorela@helsinki.fi.
authors.forename: Pia
authors.initials: P
authors.lastname: Vuorela
keywords: Chlamydia pneumoniae; antichlamydial agent; antimicrobial peptide; plant phenolics