Amphipathic beta(2,2)-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae

Show full item record



Permalink

http://hdl.handle.net/10138/164951

Citation

Hanski , L , Ausbacher , D , Tiirola , T M , Strom , M B & Vuorela , P M 2016 , ' Amphipathic beta(2,2)-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae ' PLoS One , vol. 11 , no. 6 , 0157306 . DOI: 10.1371/journal.pone.0157306

Title: Amphipathic beta(2,2)-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae
Author: Hanski, Leena; Ausbacher, Dominik; Tiirola, Terttu M.; Strom, Morten B.; Vuorela, Pia M.
Contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Faculty of Pharmacy
Date: 2016-06-09
Language: eng
Number of pages: 15
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/164951
Abstract: We demonstrate in the current work that small cationic antimicrobial beta(2,2)-amino acid derivatives (Mw <500 Da) are highly potent against Chlamydia pneumoniae at clinical relevant concentrations (<5 mu M, i.e. <3.4 mu g/mL). C. pneumoniae is an atypical respiratory pathogen associated with frequent treatment failures and persistent infections. This gram-negative bacterium has a biphasic life cycle as infectious elementary bodies and proliferating reticulate bodies, and efficient treatment is challenging because of its long and obligate intracellular replication cycle within specialized inclusion vacuoles. Chlamydicidal effect of the beta(2,2)-amino acid derivatives in infected human epithelial cells was confirmed by transmission electron microscopy. Images of infected host cells treated with our lead derivative A2 revealed affected chlamydial inclusion vacuoles 24 hours post infection. Only remnants of elementary and reticulate bodies were detected at later time points. Neither the EM studies nor resazurin-based cell viability assays showed toxic effects on uninfected host cells or cell organelles after A2 treatment. Besides the effects on early intracellular inclusion vacuoles, the ability of these beta(2,2)-amino acid derivatives to suppress Chlamydia pneumoniae infectivity upon treatment of elementary bodies suggested also a direct interaction with bacterial membranes. Synthetic beta(2,2)-amino acid derivatives that target C. pneumoniae represent promising lead molecules for development of antimicrobial agents against this hard-totreat intracellular pathogen.
Subject: IN-VITRO ACTIVITY
ANTIMICROBIAL PEPTIDES
CHLAMYDOPHILA-PNEUMONIAE
DEVELOPMENTAL CYCLE
TRACHOMATIS
PROTEINS
GROWTH
CHARGE
DRUGS
CELLS
317 Pharmacy
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
journal.pone.0157306.PDF 4.432Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record