Researchers develop novel method to find new antibiotics

November 20, 2006

Bacteria are a cunning foe; at a worrisome rate, they are developing resistance to the current arsenal of antibiotic drugs. Without new drugs, society may be approaching a world reminiscent of the pre-antibiotic era, when coming down with a bacterial infection was often a matter of life or death.

The seemingly obvious solution lies in finding more microbe-killing compounds, but University of Wisconsin-Madison bacteriologist Marcin Filutowicz is taking another approach: He plans to search for new antibiotics that render virulent bacteria harmless without killing them.

"Bacteria evolve quickly; some have already acquired resistance to all clinically relevant antibiotics," says Filutowicz, professor of bacteriology in the College of Agricultural and Life Sciences. "We microbiologists have to respond with new ideas and new technologies to outsmart the evolving bugs."

Filutowicz has developed a novel method of searching for this untapped class of antimicrobial compounds. He is seeking a patent for what he plans to call "The No-Kill Strategy to Manage Infectious Disease." His invention disclosure — a key step in obtaining a patent — was recently approved by the Wisconsin Alumni Research Foundation (WARF) and the UW-Madison Graduate School, and WARF plans to file a patent application on his behalf in early 2007.

Filutowicz's approach involves looking for new drugs that render bacteria harmless by blocking the replication of — and thus eliminating — some of their DNA.

Bacterial DNA comes in two forms: chromosomal DNA, which is required for life, and plasmid DNA, which is not. The nonessential plasmid DNA contains many undesirable bacterial genes, including those that confer antibiotic resistance or lead to the production of toxins.

Filutowicz is seeking antibiotics that would selectively disrupt the replication of plasmid DNA, so that when bacteria reproduce, they would produce plasmid-free offspring that are harmless or susceptible to traditional antibiotics.

Such compounds could dramatically alter the character of some of our nastiest microbial adversaries.

"In Bacillus anthracis, the causative agent of anthrax — and some other bacteria that are used as bio-weapons — all the virulence is plasmid-encoded. So if you get rid of the plasmids, you can actually drink a cup of [the bacteria] and you'd be fine," says Filutowicz.

The best source of drugs to treat bacterial infections is bacteria themselves. Bacteria contain genes that produce antibiotics that they use to fight and communicate with other bacteria as they compete for food and other resources.

To maximize his chances of finding these plasmid-busting compounds, Filutowicz's method makes use of groundbreaking technology called metagenomics, which was developed and patented by Jo Handelsman, a UW-Madison professor of plant pathology.

Metagenomics allows access to vast amounts of bacterial genetic material that was previously inaccessible.

Before the advent of metagenomics, researchers could study only those bacteria amenable to growth in the laboratory, a mere 2 to 3 percent of known bacterial species. Metagenomics makes it possible to study those bacteria that refuse to grow under artificial laboratory conditions, allowing access to a vast reservoir of bacterial genes - including the genes of countless soil microbes.

Access to these genes is vital because, Handelsman says, "At the same time that the treatment of infectious diseases is intensifying, the discovery of new antibiotics has slowed virtually to a crawl."

Filutowicz is confident that the vastly expanded pool of genes in Handelsman's metagenomic libraries will yield new compounds that selectively inhibit replication of plasmid DNA in bacteria. These antimicrobial agents may well constitute the next generation of antibiotic drugs.

Source: by Nicole Miller, University of Wisconsin-Madison

Explore further: Real-time analysis of metabolic products

Related Stories

Real-time analysis of metabolic products

September 30, 2015

Biologists at ETH Zurich have developed a method that, for the first time, makes it possible to measure concentration changes of several hundred metabolic products simultaneously and almost in real time. The technique could ...

Scientists discover new system for human genome editing

September 25, 2015

A team including the scientist who first harnessed the revolutionary CRISPR-Cas9 system for mammalian genome editing has now identified a different CRISPR system with the potential for even simpler and more precise genome ...

Flowing electrons help ocean microbes gulp methane

September 18, 2015

Good communication is crucial to any relationship, especially when partners are separated by distance. This also holds true for microbes in the deep sea that need to work together to consume large amounts of methane released ...

Explainer: What is the molecular clock?

September 15, 2015

In the 150 years since Charles Darwin recognised the kinship of all life, scientists have worked to fulfil his dream of a complete Tree of Life. Today, the methods used to trace the evolutionary branches back through time ...

How does your microbiome grow?

September 2, 2015

It is increasingly clear that the thousands of different bacteria living in our intestinal tract - our microbiome - have a major impact on our health. But the details of the microbiome's effects are still fairly murky. A ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.