Featured Research

from universities, journals, and other organizations

How Salmonella Bacteria Protect Against Death By Iron

Date:
October 2, 2000
Source:
Howard Hughes Medical Institute
Summary:
Researchers have discovered a survival mechanism that Salmonella bacteria employ to detect and protect themselves from high levels of iron in the environment. The newly discovered iron sensor provides double-barreled protection since it allows Salmonella to fend off the antibiotic polymyxin, which is produced by a soil microbe. The research offers a hint of the tools that Salmonella calls upon to survive and thrive in hostile environments.

September 29, 2000 — Researchers have discovered a survival mechanism that Salmonella bacteria employ to detect and protect themselves from high levels of iron in the environment. The newly discovered iron sensor provides double-barreled protection since it allows Salmonella to fend off the antibiotic polymyxin, which is produced by a soil microbe. The research offers a hint of the tools that Salmonella calls upon to survive and thrive in hostile environments.

The discovery by Howard Hughes Medical Institute investigator Eduardo Groisman and colleagues at Washington University School of Medicine in St. Louis was reported in the September 29, 2000, issue of the journal Cell.

The scientists investigated the function of PmrA/PmrB, a two-component regulatory system found in Salmonella and other gram-negative bacteria. Bacteria use two-component regulatory systems to sense environmental stimuli and to respond to those stimuli by activating or repressing the expression of different genes. In the PmrA/PmrB partnership, the scientists already knew that PmrB was the sensing element of the pair, but they did not know what signal activated PmrB. "We knew that PmrA/PmrB was a regulatory system that controlled resistance to the antibiotic polymyxin B," said Groisman. "Earlier, we had established that PmrA/PmrB was activated by another two-component system called PhoP/PhoQ."

A clue to the nature of the PmrB activation signal came when the scientists compared the sensing segment of PmrB to domains of yeast and mammalian proteins that bind iron. Their studies showed that PmrB also contained protein sequences, or motifs, that could respond to iron.

"Because the PmrA/PmrB system was activated by iron, we reasoned that it must be required for growth in the presence of toxic levels of iron," said Groisman. "Similarly, the PhoP/PhoQ system is activated in low magnesium and is necessary for growth in low magnesium."

In their experiments, the scientists showed that iron specifically turns on the genes activated by PmrA. They also showed that iron binds to the periplasmic segment of the PmrB protein that extends through the cell membrane.

In studies with mutant strains of Salmonella, they found that those with malfunctioning PmrB sensor proteins that lack the periplasmic segment did not respond to extracellular iron. And, they discovered a Salmonella strain with a malfunctioning PmrA is overly sensitive to killing by iron. Groisman and his colleagues also found that iron inhibits the growth of Salmonella strains lacking functioning versions of either PmrA or PmrB, or certain genes activated by PmrA.

"It was quite a surprise that the PmrA/PmrB system responded to high iron concentrations because all the textbooks tell you that it is low iron that promotes expression of bacterial genes," said Groisman. In such responses, the bacteria are attempting to maintain sufficient internal iron concentrations for essential bacterial processes, he said.

Groisman and his colleagues found that the PmrA/PmrB system is highly sensitive to ferric iron, or Fe3+, as opposed to ferrous iron, Fe2+, which is the form found within cells. For example, they showed that treating Salmonella with chemicals that selectively scavenged Fe3+ from the cells abolished transcription of one of PmrA-regulated genes. The researchers also showed that these genes were not activated by a wide array of other positively charged atoms, called cations.

The iron concentrations that activated the protective response, said Groisman, are typical of those found in the soil and water that the bacteria encounter once they leave the gut environment of animals or humans. High iron concentrations may also be found in the stomachs of animals and humans, he said.

Iron promotes resistance to polymyxin by working through PmrA, said Groisman. The speculation is that such resistance may prove beneficial for Salmonella by protecting it against chemical assaults by the soil polymyxin-producing bacterium Paeniacillus polymyxa. This beneficial effect would have been preserved in evolution because it offers an advantage, said Groisman.

Understanding how ferric iron kills bacteria by damaging their macromolecules and how the protective genes function are going to be major challenges, said Groisman. "Our working hypothesis is that these genes modify the lipopolysaccharide that covers the surface of bacteria so that iron does not bind to them," he said.

"In addition to helping us understand the protective mechanism of Salmonella and other gram-negative bacteria—all of which possess the PmrA/PmrB system—these findings also help us understand the nature of environments where Salmonella prospers when not infecting an animal or human host," he said.


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "How Salmonella Bacteria Protect Against Death By Iron." ScienceDaily. ScienceDaily, 2 October 2000. <www.sciencedaily.com/releases/2000/09/000929072543.htm>.
Howard Hughes Medical Institute. (2000, October 2). How Salmonella Bacteria Protect Against Death By Iron. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2000/09/000929072543.htm
Howard Hughes Medical Institute. "How Salmonella Bacteria Protect Against Death By Iron." ScienceDaily. www.sciencedaily.com/releases/2000/09/000929072543.htm (accessed September 30, 2014).

Share This



More Plants & Animals News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Earth Has Lost Half Its Vertebrate Wildlife Since 1970: WWF

Earth Has Lost Half Its Vertebrate Wildlife Since 1970: WWF

Newsy (Sep. 30, 2014) A new study published by the World Wide Fund for Nature found that more than half of the world's wildlife population has declined since 1970. Video provided by Newsy
Powered by NewsLook.com
California University Designs Sustainable Winery

California University Designs Sustainable Winery

Reuters - US Online Video (Sep. 27, 2014) Amid California's worst drought in decades, scientists at UC Davis design a sustainable winery that includes a water recycling system. Vanessa Johnston reports. Video provided by Reuters
Powered by NewsLook.com
Argentina Worries Over Decline of Soybean Prices

Argentina Worries Over Decline of Soybean Prices

AFP (Sep. 27, 2014) The drop in price of soy on the international market is a cause for concern in Argentina, as soybean exports are a major source of income for Latin America's third largest economy. Duration: 01:10 Video provided by AFP
Powered by NewsLook.com
Mama Bear, Cubs Hang out in California Backyard

Mama Bear, Cubs Hang out in California Backyard

Reuters - US Online Video (Sep. 27, 2014) A mama bear and her two cubs climb trees, wrestle and take naps in the backyard of a Monrovia, California home. Vanessa Johnston reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins