Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dealing with stress: new research highlights the survival skills of disease-causing E. coli

31.01.2012
Escherichia coli bacteria thrive in the lower intestine of humans and other animals, including birds. Most are vital constituents of the healthy gut flora, but certain forms of E. coli cause a range of diseases in both humans and poultry.

In this month’s issue of the journal PLoS ONE, a team of researchers at Arizona State University’s Biodesign Institute investigates disease-causing E. coli strains known as APEC (for Avian Pathogenic E. coli). By studying circular segments of bacterial DNA known as plasmids, the group uncovered some of the tricks used by these highly adaptive organisms to survive, even in the face of daunting environmental challenges.

According to assistant research professor Melha Mellata, lead author of the current study, the research is an important step toward a more thorough understanding of the genetic underpinnings of pathogenic E. coli: “E. coli bacteria that are able to persist and cause diseases have developed multiple strategies to achieve this,” she says. “It is important to elucidate the genetic mechanisms used by these bacteria so that we can turn their own weapons against them.”

Birds, including chickens can become infected with APEC, causing colibacillosis—an acute and often fatal disease, resulting in significant economic loss for the poultry industry. Further, because APEC bacteria bear a genetic blueprint similar to that of other members of the group of Extra-intestinal pathogenic E. coli or ExPEC, to which they belong, the danger exists for such avian bacterial strains to cross the genetic barrier to infect humans, causing so-called zoonotic diseases.

Retail chicken products are also believed to act as reservoirs for existing E. coli strains responsible for human ExPEC infections. As their name implies, these extra-intestinal bacterial pathogens cause infections outside their customary habitat in the gut. They are responsible for illnesses including septicemia, newborn meningitis and urinary tract infections. ExPEC infections result in significant loss of life and cost the U.S. health care industry billions of dollars.

While the genetic kinship of human and avian pathogenic E. coli strains is cause for concern, it may also provide an opportunity for the development of a vaccine capable of cross-protecting humans and birds, if a group of genes common to all extra-intestinal E. coli can be identified and targeted. Roy Curtiss, director of Biodesign’s Center for Infectious Diseases and Vaccinology, oversees a project aimed at achieving this goal.

In the current study, the team—including undergraduate researchers, Jacob Maddux and Timothy Nam—investigated the genetic sequence of several large plasmids in a strain of APEC commonly used for research purposes. The presence of multiple large plasmids is characteristic of ExPEC bacteria, particularly APEC. Previously, the first of three large plasmids had been sequenced and analyzed by the group and found to code for virulence factors, which help the bacterium infect its host. The two other large plasmids were sequenced for the first time in the present study, as well as a smaller APEC plasmid, whose significance remains obscure.

Unlike the first of the three large plasmids examined, the second and third do not encode for common virulence factors and appear to play only a minor role in the actual infection process of APEC bacteria. The team hypothesized that these plasmids instead conferred heightened survival potential during stressful environmental situations, including bacterial subsistence soils, poultry litter or under acidic conditions.

In order to test the hypothesis, the group began by fully sequencing these two large plasmids as well as a smaller plasmid. They next examined the contribution of all four plasmids, both individually and in combination, as the APEC bacteria colonized human intestinal epithelial cells. The APEC strains, with their complement of plasmids, were studied under varying environmental conditions to assess their resistance to acid and bile in the human GI tract; growth under iron-poor conditions and varying carbon sources; and ability to clump together to form biofilms—a critical component of the infection process.

In order to study the role of plasmids on APEC interaction with enteric cells, the group used a 3-D cell culture model of human intestinal epithelium, which has been shown to more accurately mimic the structure-function of the in vivo tissue than traditional monolayer cultures. Cheryl Nickerson’s research group at the Biodesign Institute®—participants in the current study—have worked extensively in the development and application of 3-D cell cultures as human surrogate infection models. The application of these advanced enteric models to dissect the molecular mechanisms of APEC pathogenesis was a logical choice for these studies.

The large plasmids under investigation did not appear to have a significant effect on the ability of APEC-derived strains to associate with and invade human intestinal epithelial cells. Further experiments however implicated large plasmids—for the first time—in APEC’s ability to resist acid and bile, two critically important tools for E. coli survival, particularly under the low pH conditions found in certain foods and in the stomach.

Many pathogenic bacteria, APEC included, form aggregates of material known as biofilms. Biofilms are implicated in 65-80 percent of human infections. Their mechanisms of formation are therefore a matter of considerable medical concern. ExPEC cells form biofilm concentrations in both the gastrointestinal and urinary tracts. By examining the function of three large plasmids in biofilm formation (separately and in combination) at varying temperatures, the group was able to tease out some of the key features of ExPEC biofilm formation. They found that 4 distinct kinds of biofilm formed under the influence of the large plasmids, depending on temperature conditions.

Plasmid-driven biofilm formation may play an essential role in the virulence of APEC and other ExPEC forms, by conveying survival advantages in various environmental niches found in the host. Likewise, the means by which ExPEC bacteria are able to modify their metabolism to make use of available nutrients is an important factor in their pathogenesis. A gene cluster located on one of the large plasmids was found to code for an alternate sugar pathway, again improving the pathogen’s prospects for survival under changing nutrient conditions. (Intriguingly, the gene cluster does not occur in other forms of E. coli, though it is present in another important pathogen—Salmonella.)

The combined results are a significant advance toward a comprehensive understanding of extra-intestinal E. coli pathogens and their mechanisms of survival. In earlier work, assistant research professor Mellata generated vaccine candidates specifically targeting APEC infection. The current research improves the prospects for a new range of vaccine candidates conveying cross protection from ExPEC infections in both human and avian populations. “We are very confident that our strategy in designing a much broader vaccine targeting multiple subgroups of pathogenic E. coli will result in positive health and economic impacts,” Melha says.

In addition to their appointments at the Biodesign Institute, Roy Curtiss and Cheryl Nickerson are professors in the College of Liberal Arts and Sciences, School of Life Sciences.

Written by: Richard Harth
Science Writer: The Biodesign Institute
richard.harth@asu.edu

Joseph Caspermeyer | EurekAlert!
Further information:
http://www.asu.edu

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Individualized fiber components for the world market

23.06.2017 | Physics and Astronomy

How brains surrender to sleep

23.06.2017 | Life Sciences

Can we see monkeys from space? Emerging technologies to map biodiversity

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>