New imagining technique could lead to better antibiotics and cancer drugs

November 09, 2009

COLLEGE STATION - A recently devised method of imaging the chemical communication and warfare between microorganisms could lead to new antibiotics, antifungal, antiviral and anti-cancer drugs, said a Texas AgriLife Research scientist.

"Translating metabolic exchange with imaging mass spectrometry," was published Nov. 8 in Nature Chemical Biology, a prominent scientific journal. The article describes a technique developed by a collaborative team that includes Dr. Paul Straight, AgriLife Research scientist in the department of biochemistry and biophysics at Texas A&M University in College Station, Dr. Pieter Dorrestein, Yu-Liang Yang and Yuquan Xu, all at the University of California, San Diego.

"Microorganisms encode in their genomes the capacity to produce many small molecules that are potential new antibiotics," Straight said. "Because we do not understand the circumstances under which those molecules are produced in the environment, we see only a small fraction of them in the laboratory."

An example is the antibiotic erythromycin, which is often prescribed for people who are allergic to penicillin, Straight said.

"We know that Saccharopolyspora erythraea, the bacteria from which erythromycin is derived, encodes the capacity to produce numerous other small molecules that might be potentially valuable drugs," he said. "Conventional microbial culture and drug discovery techniques uncovered erythromycin. Other potentially useful metabolites may require some unconventional methods for identification."

Historically, medicinal drugs have been discovered serendipitously or by finding the active ingredient in homeopathic remedies, Straight said. For example, the use of blue mold for treating wounds was a folk remedy dates back to the Middle Ages. But scientists didn't isolate and purify the active ingredient, penicillin, until the early 20th century, which marks the beginning of the era of 'natural product' medicines originating from microorganisms.

Modern methods of drug discovery rely on screening technologies, knowledge of how infection is controlled and why diseases originate at the molecular level. Some new drugs can be designed accordingly from the ground up, often at significant cost, but serendipitous discovery of what nature has to offer is still a valid approach, he said.

Microorganisms, such as the bacteria that produces erythromycin, have been communicating and battling with each other for millennia using similar small molecules.

"What we learn about how microbes interact and exchange chemicals, and how the presence of one signaling molecule or antibiotic changes the output of potential antibiotics from a neighboring microbe, will guide us to new strategies for boosting the number of potential therapeutic drugs from any given bacteria," Straight said.

The National Institutes of Health recognizes the need to boost development of new drug compounds, he said.

"Globally, there is a shortage of new antibiotics that are being discovered by pharmaceutical companies in the traditional way and an ever-increasing number of multiple drug-resistant pathogens and newly emerging pathogens," Straight said.

The method of Straight, Dorrestein and colleagues employed an instrument called a "matrix-assisted laser desorption/ionization mass spectrometer." The device ionizes part of the sample with a laser beam while a crystalline matrix prevents the bio-molecules from being destroyed.

The plate upon which the bio sample sits is moved during the scan, from which hundreds to thousands of spectra are collected. The data is then processed as a grid and rendered as false-color by computer, then overlaid on a visual image of the sample.

Straight, Dorrestein and colleagues used two common bacteria that are cultured in the laboratory for their tests, Bacillus subtilis and Steptomyces coelicolor, both commonly found in soils. The bacteria were cultured together and their complex chemical interaction recorded using the mass spectrometer.

In competition for resources, the bacteria produced small molecules that alter antibiotic production from patterns present when cultured separately, Straight said. For example, they found that production of an antibiotic that targets Gram-positive organisms (Streptococcus and Staphylococcus are examples of Gram-positive organsims) was inhibited in one bacteria by the other.

The data reveal the chemical complexity of interspecies encounters. Using genetic sequencing, the researchers found that bacteria may dedicate up to 20 percent of their DNA to the bio-synthesis of small molecules in their communications and chemical battles with other microorganisms.
-end-


Texas A&M AgriLife Communications

Related Bacteria Articles from Brightsurf:

Siblings can also differ from one another in bacteria
A research team from the University of Tübingen and the German Center for Infection Research (DZIF) is investigating how pathogens influence the immune response of their host with genetic variation.

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.

Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.

Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.

Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.

Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.

How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.

The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.

Read More: Bacteria News and Bacteria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.