Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New target found for nitric oxide's attack on salmonella bacteria

25.07.2011
Naturally produced by the body, nitric oxide disrupts pathogens' metabolism

A new target for nitric oxide has been revealed in studies of how it inhibits the growth of Salmonella. This bacterium is a common cause of food-poisoning.

"Nitric oxide is naturally produced in the nose and the gut and other tissues in the body to ward off infection," explained the senior author of the paper, Dr. Ferric Fang. He is a University of Washington (UW) professor of laboratory medicine, microbiology and medicine.

Nitric oxide – not to be confused with nitrous oxide, the laughing gas in dentists' offices – is similar to the preservatives in hotdogs, Fang said. Reactive nitrogen species, like nitric oxide, make brown meat an appetizing pink. They also weed out microorganisms that spoil food or cause food poisoning.

Fang's lab has made several important discoveries on ways mammals exploit the biochemical properties of nitric oxide to defend themselves from germs. Nitric oxide, a key actor in the body's innate immune defenses, apprehends a rogue's gallery of disease-causing organisms.

The newest results underscore that nitric oxide's antimicrobial actions are due to its interference with the metabolism, or energy production, of pathogens.

"Nitric oxide imposes substantial metabolic restrictions on bacteria," the researchers noted. Fang explained that its reactions with numerous metabolic targets accounts for the broad-spectrum nature of its success. It keeps many types of disease-causing bacteria at bay. It also prevents an overgrowth of the body's many helpful bacteria.

The latest report on the versatility of nitric oxide in arming hosts against pathogens is published in the July 21 issue of Cell Host & Microbe. Dr. Anthony R. Richardson, who is now at the University of North Carolina at Chapel Hill, led the research while he was a postdoctoral fellow in the Fang lab.

Fang's team looked at the multi-pronged action of nitric oxide on Salmonella enterica serovar Typhimurium. This type of Salmonella can contaminate food and is similar to the bacteria that cause typhoid fever.

Nitric oxide and related chemicals put Salmonella into a difficult situation called nitrosative stress. When exposed to nitric oxide, Salmonella is unable to make two essential amino acids, methionine and lysine.

Without these, Salmonella cannot grow.

"This is bad news for the bacteria, but not for the host," Fang said. "Nitric oxide doesn't damage the host that produces it."

The ability to withstand nitrosative stress makes some forms of bacteria more virulent than milder types that can't handle it.

Richardson and his colleagues found that nitric oxide and its cousins throw a monkey wrench into several points in the Krebs cycle, also known as the tricarboxylic acid cycle. This cycle is the second stage in cellular respiration, when fuel is broken down to release energy for cell growth and division.

The researchers outlined how multiple interruptions in this cycle create a series of biochemical consequences that starve Salmonella of methionine and lysine. Nitric oxide also blocks certain regulatory genes that otherwise would give Salmonella an alternate chemical route out of its distress.

"Collectively, this work demonstrates that nitric oxide imposes substantial metabolic restrictions on bacteria," the authors concluded.

In a commentary on these findings, Dr. Stephen Spiro of the Department of Molecular and Cell Biology at the University of Texas at Dallas wrote that the work "focuses renewed interest in central metabolic pathways as nitric oxide targets."

"More generally," he noted, "this study provides an excellent illustration that a proper understanding of host-pathogen interactions and the development of therapeutic interventions require a detailed knowledge of pathogen metabolism."

Nitric oxide's targeting of the Krebs cycle is not unique to Salmonella. In learning how the body naturally controls the energy supplies and growth of varied disease-causing organisms, Fang said, scientists may be able to develop new broad-spectrum antimicrobials that mimic these effects, drugs that promote the body's own natural defenses against infection, or agents that overcome the ways virulent bacteria compensate when being starved of certain nutrients.

In addition to Richardson and Fang, the UW researchers on the study "Multiple Targets of Nitric Oxide of the Tricarboxylic Acid (TCA) Cycle of Salmonella enterica Serovar Typhimurium" were Elizabeth C. Payne, Noah Younger, Joyce E. Karlinsey, Vinai Thomas, Lynne Becker, William W. Navarre, Margaret E. Castor and Stephen J. Libby.

The research was supported by grants from the National Institutes of Health.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

Further reports about: Salmonella amino acid cell death nitric nitric oxide

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>