• norsk
    • English
  • English 
    • norsk
    • English
  • Login
View Item 
  •   Home
  • Øvrige samlinger
  • Publikasjoner fra CRIStin - NTNU
  • View Item
  •   Home
  • Øvrige samlinger
  • Publikasjoner fra CRIStin - NTNU
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

A novel antimycobacterial compound acts as an intracellular iron chelator

Dragset, Marte Singsås; Poce, Giovanna; Alfonso, Salvatore; Padilla-Benavides, Teresita; Ioerger, Thomas R.; Kaneko, Takushi; Sacchettini, James C.; Biava, Mariangela; Parish, Tanya; Argüello, José M.; Steigedal, Magnus; Rubin, Eric J.
Journal article, Peer reviewed
Accepted version
Thumbnail
View/Open
2256.full.pdf (2.601Mb)
URI
http://hdl.handle.net/11250/2456935
Date
2015
Metadata
Show full item record
Collections
  • Institutt for bioteknologi og matvitenskap [1721]
  • Institutt for klinisk og molekylær medisin [3859]
  • Publikasjoner fra CRIStin - NTNU [41955]
Original version
Antimicrobial Agents and Chemotherapy. 2015, 59 (4), 2256-2264.   10.1128/AAC.05114-14
Abstract
Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis. Mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. Resistance mutations against a novel pyrazolopyrimidinone compound (PZP) that is active against M. tuberculosis have been identified within the gene cluster encoding the ESX-3 type VII secretion system. ESX-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, which could indicate that PZP restricts mycobacterial growth by targeting ESX-3 and thus iron uptake. Surprisingly, we show that ESX-3 is not the cellular target of the compound. We demonstrate that PZP indeed targets iron metabolism; however, we found that instead of inhibiting uptake of iron, PZP acts as an iron chelator, and we present evidence that the compound restricts mycobacterial growth by chelating intrabacterial iron. Thus, we have unraveled the unexpected mechanism of a novel antimycobacterial compound.
Publisher
American Society for Microbiology
Journal
Antimicrobial Agents and Chemotherapy

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit
 

 

Browse

ArchiveCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDocument TypesJournalsThis CollectionBy Issue DateAuthorsTitlesSubjectsDocument TypesJournals

My Account

Login

Statistics

View Usage Statistics

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit