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Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis.

Abstract：

:Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compounds with extremely high Fe3+ affinity. Several lines of evidence suggest that siderophores have a critical role in bacterial iron acquisition inside the human host, where the free iron concentration is well below that required for bacterial growth and virulence. Thus, siderophore biosynthesis is an attractive target in the development of new antibiotics to treat tuberculosis and plague. In particular, such drugs, alone or as part of combination therapies, could provide a valuable new line of defense against intractable multiple-drug-resistant infections. Here, we report the design, synthesis and biological evaluation of a mechanism-based inhibitor of domain salicylation enzymes required for siderophore biosynthesis in M. tuberculosis and Y. pestis. This new antibiotic inhibits siderophore biosynthesis and growth of M. tuberculosis and Y. pestis under iron-limiting conditions.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Ferreras JA,Ryu JS,Di Lello F,Tan DS,Quadri LE

doi

10.1038/nchembio706

keywords:

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

29-32

issue

1

eissn

1552-4450

issn

1552-4469

pii

nchembio706

journal_volume

1

pub_type

杂志文章

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