dc.contributor.author | Hanski, Leena | |
dc.contributor.author | Ausbacher, Dominik | |
dc.contributor.author | Tiirola, Terttu | |
dc.contributor.author | Strøm, Morten B. | |
dc.contributor.author | Vuorela, Pia M. | |
dc.date.accessioned | 2017-01-30T14:17:53Z | |
dc.date.available | 2017-01-30T14:17:53Z | |
dc.date.issued | 2016-06-09 | |
dc.description.abstract | We demonstrate in the current work that small cationic antimicrobial β2,2-amino acid derivatives
(Mw < 500 Da) are highly potent against Chlamydia pneumoniae at clinical relevant
concentrations (< 5 μM, i.e. < 3.4 μg/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 β2,2-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 β2,2-amino acid derivatives to suppress Chlamydia pneumoniae
infectivity upon treatment of elementary bodies suggested also a direct interaction with bacterial
membranes. Synthetic β2,2-amino acid derivatives that target C. pneumoniae represent
promising lead molecules for development of antimicrobial agents against this hard-totreat
intracellular pathogen. | en_US |
dc.description | Copyright: © 2016 Hanski et al. This is an open
access article distributed under the terms of the <a href="https://creativecommons.org/licenses/by/4.0/">
Creative Commons Attribution License</a>, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
<a href="http://www.dx.doi.org/10.1371/journal.pone.0157306">DOI: 10.1371/journal.pone.0157306</a> | en_US |
dc.identifier.citation | Hanski L, Ausbacher D, Tiirola T, Strøm mbs, Vuorela PM. Amphipathic β2,2-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia Pneumoniae. PLoS ONE. 2016;11(6) | en_US |
dc.identifier.cristinID | FRIDAID 1360670 | |
dc.identifier.doi | 10.1371/journal.pone.0157306 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | https://hdl.handle.net/10037/10232 | |
dc.language.iso | eng | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.journal | PLoS ONE | |
dc.rights.accessRights | openAccess | en_US |
dc.subject | VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Klinisk kjemi: 725 | en_US |
dc.subject | VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Clinical chemistry: 725 | en_US |
dc.title | Amphipathic β2,2-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia Pneumoniae | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |