JAC Advance Access published online on October 27, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn436
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Original research |
The cell-penetrating peptide, Pep-1, has activity against intracellular chlamydial growth but not extracellular forms of Chlamydia trachomatis
1 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA 2 Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697-4025, USA 3 Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-4025, USA 4 Department of Medicine, University of California, Irvine, CA 92697-4025, USA
Received 20 June 2008; returned 19 July 2008; revised 12 September 2008; accepted 24 September 2008
* Correspondence address. Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA. Tel: +1-949-824-3397; Fax: +1-949-824-8598; E-mail: mingt{at}uci.edu
Objectives: In the course of studies to identify novel treatment strategies against the pathogenic bacterium, Chlamydia, we tested the carrier peptide, Pep-1, for activity against an intracellular infection.
Methods: Using a cell culture model of Chlamydia trachomatis infection, the effect of Pep-1 was measured by incubating the peptide with extracellular chlamydiae prior to infection, or by adding Pep-1 to the medium at varying times after infection, and assaying for inhibition of inclusion formation.
Results: Pep-1 had a concentration-dependent effect on chlamydial growth with 100% inhibition of inclusion formation at 8 mg/L peptide. There was a window of susceptibility during the chlamydial developmental cycle with a maximal effect when treatment was begun within 12 h of infection. Pep-1 treatment caused a severe reduction in the production of infectious progeny even when started later, when the effect on inclusion formation was minimal. Furthermore, electron micrographs showed a paucity of progeny elementary bodies (EBs) in the inclusion. In contrast, pre-incubation of EBs with Pep-1 prior to infection did not affect inclusion formation. Taken together, these findings indicate that the antichlamydial effect was specific for the intracellular stage of chlamydial infection. By comparison, Pep-1 had no antimicrobial activity against Escherichia coli and Staphylococcus aureus or the obligate intracellular parasite, Toxoplasma gondii.
Conclusions: Pep-1 has antichlamydial activity by preventing intracellular chlamydial growth and replication but has no effect on extracellular chlamydiae.
Key Words: Chlamydia spp. , antimicrobial peptides , antimicrobial activity , antimicrobial agents