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Keywords
(8)
Biological Systems
Essential Gene
Lipoprotein
Mechanism of Action
multidrug resistance
pseudomonas aeruginosa
Escherichia Coli
Gram Negative
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Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting
Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting,10.1038/nchembio.221,Nature Chemical Biology,Ranjana
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Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting
(
Citations: 9
)
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Ranjana Pathania
,
Soumaya Zlitni
,
Courtney Barker
,
Rahul Das
,
David A Gerritsma
,
Julie Lebert
,
Emilia Awuah
,
Giuseppe Melacini
,
Fred A Capretta
,
Eric D Brown
One of the most significant hurdles to developing new chemical probes of
biological systems
and new drugs to treat disease is that of understanding the
mechanism of action
of small molecules discovered with cell-based small-molecule screening. Here we have assembled an ordered, high-expression clone set of all of the essential genes from
Escherichia coli
and used it to systematically screen for suppressors of growth inhibitory compounds. Using this chemical genomic approach, we demonstrate that the targets of well-known antibiotics can be identified as high copy suppressors of chemical lethality. This approach led to the discovery of MAC13243, a molecule that belongs to a new chemical class and that has a unique mechanism and promising activity against multidrug-resistant Pseudomonas aeruginosa. We show that MAC13243 inhibits the function of the LolA protein and represents a new chemical probe of
lipoprotein
targeting in bacteria with promise as an antibacterial lead with Gram-negative selectivity.
Journal:
Nature Chemical Biology - NAT CHEM BIOL
, vol. 5, no. 11, pp. 849-856, 2009
DOI:
10.1038/nchembio.221
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Citation Context
(3)
... Extending these studies to antibacterial compounds of unknown mechanism led to the discovery of a new lipoprotein-targeting inhibito
...
Shannon B Falconer
,
et al.
Antibiotics as probes of biological complexity
... coli to determine the MOA of bioactive agent
...
Julian Davies
,
et al.
Bugs, drugs and chemical genomics
...166,
...
Xiangyang Liu
,
et al.
Bioprospecting microbial natural product libraries from the marine env...
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Citations
(9)
Antibiotics as probes of biological complexity
Shannon B Falconer
,
Tomasz L Czarny
,
Eric D Brown
Journal:
Nature Chemical Biology - NAT CHEM BIOL
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Bugs, drugs and chemical genomics
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