Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

New Drugs Block Synthesis of Metabolites by Nutrient-Challenged Bacteria

By BiotechDaily International staff writers
Posted on 24 Oct 2013
Print article
Researchers have developed a new generation of antibiotics that kill bacteria by preventing them from making critical metabolites such as vitamins and amino acids.

Characterizing new drugs has been hindered by the difficulties inherent in identifying the mechanism of action (MOA) of biologically active molecules. To attack this problem, investigators at McMaster University (Hamilton, ON, Canada) developed a metabolite suppression approach to explore the MOA of antibacterial compounds under conditions of nutrient restriction.

They assembled an array of metabolites that could be screened for suppressors of inhibitory molecules. Further, they identified inhibitors of Escherichia coli growth under nutrient limitation and charted their interactions with the metabolite array. This strategy led to the discovery and characterization of three new antibacterial compounds, MAC168425 (3-(dimethylamino)-1-(4-methoxyphenyl)propan-1-one), MAC173979 (3,3-dichloro-1-(3-nitrophenyl)prop-2-en-1-one), and MAC13772 (2-(2-nitrophenylthio)acetohydrazide). MAC168425 was found to interfere with glycine metabolism, MAC173979 was a time-dependent inhibitor of p-aminobenzoic acid biosynthesis, and MAC13772 inhibited biotin biosynthesis. These findings were published in the October 13, 2013, online edition of the journal Nature Chemical Biology.

"We have developed technology to find new antibiotics using laboratory conditions that mimic those of infection in the human body," said senior author Dr. Eric Brown, professor of biochemistry and biomedical sciences at McMaster University.

"We are taking fresh aim at bacterial vitamin and amino acid production and finding completely novel antibacterial compounds," said Dr. Brown. "We threw away chemicals that blocked growth in conventional nutrient-rich conditions and focused instead on those that were only active in nutrient-poor conditions. The approach belies conventional thinking in antibiotic research and development, where researchers typically look for chemicals that block growth in the laboratory under nutrient-rich conditions, where vitamins and amino acids are plentiful, but in the human body these substances are in surprisingly short supply and the bacteria are forced to make these and other building blocks from scratch."

Related Links:

McMaster University



Print article

Channels

Genomics/Proteomics

view channel
Image: The green-labeled cells show a basal cell carcinoma in mouse tail epidermis derived from a single mutant stem cell and expanding out of the normal epidermis stained in red (Photo courtesy of Adriana Sánchez-Danés, Université Libre de Bruxelles).

Stem Cells Not Progenitors Can Trigger Skin Cancer Growth

Cancer researchers have discovered that stem cells can initiate development of malignant skin tumors, while progenitor cells are limited to triggering only benign growths. A progenitor cell is similar... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Lab Technologies

view channel
Image: A 3D nanofiber net formed by the supergelators to trap oil molecules (Photo courtesy of IBN at A*STAR / Institute of Bioengineering and Nanotechnology).

Effective Cleanup with Smart Material That Forms Oil-Trapping Net

Researchers have developed supergelators – an organic oil-scavenging material that rapidly forms a 3D net to trap oil molecules, gelatinizing into solidified masses that can be more easily removed from... Read more

Business

view channel

Sartorius Acquires US Start-up ViroCyt

Sartorius AG (Göttingen, Germany), a pharmaceutical and laboratory equipment provider, has acquired ViroCyt Incorporated (Broomfield, CO, USA), a start-up in the field of rapid virus quantification, in a deal valued at approximately USD 16 million. ViroCyt’s automated platform integrates instruments, software and reagents... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.