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 New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>