title: Engineered phage-based therapeutic materials inhibit Chlamydia trachomatis intracellular infection.
abstract: Developing materials that are effective against sexually transmitted pathogens such as Chlamydia trachomatis (Ct) and HIV-1 is challenging both in terms of material selection and improving bio-membrane and cellular permeability at desired mucosal sites. Here, we engineered the prokaryotic bacterial virus (M13 phage) carrying two functional peptides, integrin binding peptide (RGD) and a segment of the polymorphic membrane protein D (PmpD) from Ct, as a phage-based material that can ameliorate Ct infection. Ct is a globally prevalent human pathogen for which there are no effective vaccines or microbicides. We show that engineered phage stably express both RGD motifs and Ct peptides and traffic intracellularly and into the lumen of the inclusion in which the organism resides within the host cell. Engineered phage were able to significantly reduce Ct infection in both HeLa and primary endocervical cells compared with Ct infection alone. Polyclonal antibodies raised against PmpD and co-incubated with constructs prior to infection did not alter the course of infection, indicating that PmpD is responsible for the observed decrease in Ct infection. Our results suggest that phage-based design approaches to vector delivery that overcome mucosal cellular barriers may be effective in preventing Ct and other sexually transmitted pathogens.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors.forename: Shanta Raj
authors.initials: SR
authors.lastname: Bhattarai
authors.forename: So Young
authors.initials: SY
authors.lastname: Yoo
authors.forename: Seung-Wuk
authors.initials: SW
authors.lastname: Lee
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
mesh_terms: D017104:Bacteriophage M13 / Q000235:genetics*; D002690:Chlamydia Infections / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000302:isolation & purification*; D006367:HeLa Cells; D006801:Humans; D009842:Oligopeptides
chemical_list: D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid