Bacteriophage
genomics method to antimicrobial drug discovery published
Bacterial
Viruses; Bacteriophage genomics method to antimicrobial drug discovery
published;
Drug Week 02-13-2004
Bacterial Viruses; Bacteriophage genomics method to antimicrobial drug
discovery published
ISSN: 15316440
Publication Date: 02-13-2004
Page: 38
Type: Periodical
Language: English
2004 FEB 13 - (NewsRx.com & NewsRx.net) -- Identifying the
targets that bacterial viruses, or phages, use to halt bacterial growth and
then screening against those targets for small molecule inhibitors that attack
the same targets provides a unique platform for the discovery of novel
antibiotics.
Researchers from Montreal-based PhageTech, Inc., describe in
the February issue of Nature Biotechnology this novel method for discovering new
classes of antibiotics.
"Over the course of evolution, the multitudes of phages
that attack bacteria have developed unique proteins that bind to and inactivate
(or redirect) critical cellular targets within their prey," said Jing Liu,
PhD, corresponding author of the publication. "This binding shuts off key
metabolic processes in the bacteria, diverting those organisms from their own
growth and reproduction to the production of new phage progeny. We believe
these phage- identified bacterial 'weak spots' will provide useful screening
targets for discovering the sorts of truly novel antibiotics needed to combat
growing antibiotic resistance."
The publication's authors used a high-throughput phage genomics
strategy to identify novel 31 novel polypeptide families that inhibit
Staphylococcus aureus growth when expressed in the bacteria. Several of these
were found to attack targets essential for bacterial DNA replication or
transcription. They then employed the interaction between a prototypic phage
peptide, ORF104 of phage 77, and its bacterial target, DnaI, to screen for
small molecule inhibitors. Using this strategy, the researchers found several
novel compounds that inhibited both bacterial growth and DNA synthesis.
"This strategy offers several benefits as a novel approach
to antimicrobial drug discovery," said Jinzi J. Wu, MD, PhD, PhageTech
vice president, R&D - biology. "First, the bacterial targets
identified in this manner are evolutionarily validated as important to
bacterial growth and potentially susceptible to inactivation by small molecule
drugs. This allows us to quickly pinpoint the most promising anti-microbial
targets from among thousands of possible candidates. Second, this approach
provides a ready-to-use screening assay based on inhibition of interactions
between a phage peptide and its bacterial target."
"The fight against growing bacterial resistance requires
new classes of antibiotics against novel targets. Our strategy of screening for
compounds that address the same antibacterial targets attacked by phages is a
very good way of identifying novel compounds against many different bacterial
species," concluded Wu.
Applying its novel antibiotic discovery platform, PhageTech has
identified eight novel antimicrobial targets against which the company is
screening chemical libraries and applying medicinal chemistry to further refine
and evaluate those inhibitors. PhageTech has also continued to expand its phage
genomics platform from Staphylococcus aureus to other bacterial pathogens
including Streptococcus pneumoniae and Pseudomonas aeruginosa.
This article was prepared by Drug Week editors from staff and
other reports. Copyright 2004, Drug Week via NewsRx.com & NewsRx.net.
Copyright 2004, Drug Week via NewsRx.com & NewsRx.net
