Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tiny Natural Pirates Fight Multi-Resistant Pathogens

13.03.2014

Bacteriophages Offer New Strategic Options in Battling Multi-Resistant Achromobacter xylosoxidans

Infections with the often multi-resistant pathogen Achromobacter xylosoxidans are reported more and more frequently.


Adsorption of phage JWAlpha to Achromobacter DSM 11852 cells (Scanning electron micrograph) Sample was taken 5 min after pahge application. Adsorbed Phages are coloured in red.

@HZI (M.Rohde), DSMZ (J.Wittmann)


Bacteriophages are viruses that infect and replicates within bacteria (Achromobacter 90 min after infection with alpha phages)

@HZI (M.Rhode), DSMZ (J.Wittmann)

This opportunistic pathogen is for example involved in cystic fibrosis, a metabolic disorder for which no cure exists. Bacteriophages (phages for short) are natural enemies of bacteria and might provide an alternative way of effectively fighting infections, in particular hospital-acquired infections.

Johannes Wittmann, a researcher at Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures, Braunschweig (Brunswick), Germany, has isolated and thoroughly studied various phages targeting Achromobacter xylosoxidans. His is the first study presenting a large number of diverse phages that might be used to fight this pathogen.

Further studies investigating their therapeutic potential are under way. Initial results have just been published in the scientific journals PLOS One and Virology Journal.

iruses targeting bacteria are referred to as bacteriophages, or phages for short. They have become a focus of scientific interest for rather practical reasons: As antibiotics are losing, at an alarming rate, their effectiveness in fighting multi-resistant bacterial pathogens, these natural enemies of bacteria are becoming more and more important. This is where current basic research at DSMZ, conducted by a team led by scientists Johannes Wittmann and Christine Rohde, comes into play.

“As the name bacteriophages (which is derived from the Greek ‘phagos,’ meaning ‘glutton’) suggests, these viruses ‘devour’ bacteria, effectively destroying them,” as Johannes Wittmann, a postdoctoral researcher at DSMZ, explains. “They achieve this by using a sophisticated system. The virus injects its genetic material into the bacterial cell where it is ‘read’ by the protein-making mechanisms of the bacterium, essentially reprogramming it. In this way, the phages, like tiny pirates, ‘hijack’ the bacterial cell. 

The result is the production of countless new phages. Eventually, the host cell bursts, releasing hundreds of these viruses, which in turn may destroy more bacteria.”

A new strategy for battling multi-resistant pathogens

This effective mechanism of action employed by phages, plus the fact that they are harmless to humans, might make bacteriophages a weapon in the fight against various multi-resistant infectious agents. “Phages are particularly suited to fighting pathogens because they each target only one specific species of host bacteria,” says Johannes Wittmann. “You might think of them as ‘intelligent’, self-limiting medications. They will replicate only at the site of bacterial infection, and they will do so only until all host bacteria have been used up.”

At the center of this first comprehensive scientific study of phages at DSMZ is the mobile gram-negative rod-shaped bacterium Achromobacter xylosoxidans, an opportunistic pathogen that so far has not been sufficiently investigated. Achromobacter xylosoxidans is wide spread in our natural environment, occurring both in soil and various water sources. While often harmless, it may cause severe infections, such as endocarditis, bacteriemia, and meningitis, in people with compromised immune systems.

“In medicine, the often multi-resistant pathogen Achromobacter plays a not to be ignored role in cystic fibrosis, a tragic metabolic disorder for which no cure exists today,” says Johannes Wittmann. “In patients with cystic fibrosis, this bacterium is one of several species forming biofilms in the affected lungs. These biofilms are more accessible to phages than to antibiotics. It is just these opportunistic pathogens that have hospital staff worried. We therefore consulted on this project with Charité, the Berlin university hospital.”

“We are seeing an increase in patients with opportunistic infections in recent years,” comments Professor Martin Witzenrath of the Department of Infectious Diseases and Respiratory Medicine at Charité. “In this context, pathogens that are resistant to common antibiotics such as penicillin, macrolides, and cephalosporins, present us with major therapeutic challenges. From a clinical point of view, Achromobacter is problematic as well, in particular in patients with cystic fibrosis, and we fear that we will see it much more often in the future. This illustrates an urgent unmet need for fighting pathogens that are resistant to antibiotics. Wittmann’s current study presents an important example of a new alternative strategy.”

New phages targeting Achromobacter

“Phages are best found in the same places that are inhabited by the pathogens that we suspect them to be effective against, e.g., in waste water. We have been able to readily isolate phages targeting Achromobacter from municipal water treatment plants. For screening purposes, we incubated filtrates from the plant with the host bacteria,” recalls Johannes Wittmann. “Plaques forming in the bacterial lawn on the agar plates then showed us where we would find the matching phages.”

A widely diverse range of more than 60 strains of the genus Achromobacter was used as host bacteria. They were taken from the DSMZ’s own collection as well as from culture collections in Sweden, the Czech Republic, Belgium, and Canada. Most of the strains had been isolated from clinical samples such as sputum, blood, and urine, or from the environment. They all exhibited resistance to antibiotics commonly used in hospitals. 

A total of 34 phages were isolated and characterized, and some of their genetic material has already been sequenced at DSMZ. “We were very surprised to discover that two phages belong to the rare family of N4-like phages,” says Wittmann.

“More studies are needed to test Achromobacter targeting phages for their usefulness as therapeutic phages. Then they would be added to the collection of therapeutic phages at DSMZ,” explains Christine Rohde, head of the working group. “These studies include the sequencing of the entire phage genome in order to exclude genes encoding for undesirable properties.”

The Phage Collection at DSMZ:

The specialized phage collection currently contains about 350 phages targeting a wide range of bacteria. Phages are of interest to humans because they are so closely associated with (and limited to) their individual bacterial hosts. Thus, they can be used to fight harmful bacteria, with applications in animal husbandry, agriculture, food production, and medical therapy.
https://www.dsmz.de/catalogues/catalogue-microorganisms/groups-of-organisms-and-...

DSMZ information on phages online:

DSMZ offers information on phages and their therapeutical use online at: https://www.dsmz.de/home/info-on-phages.html

Original publications:

J. Wittmann et al.: Isolation and Characterization of Numerous Novel Phages Targeting Diverse Strains of the Ubiquitous and Opportunistic Pathogen Achromobacter xylosoxidans. PLOSone (2014) http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0086935

J. Wittmann et.al : First genome sequences of Achromobacter phages reveal new members of the N4 family. Virology Journal 2014, 11:14 http://www.virologyj.com/content/11/1/14

Additional literature:

C. Rohde & J. Sikorski: Bakteriophagen – Vielfalt, Anwendung und ihre Bedeutung für die Wissenschaft vom Leben. Naturwiss. Rundschau (2011) 751, 5 – 14 (in German)

J. Garbe et al. (2010): Characterization of JG024, a pseudomonas aeruginosa PB1-like broad host range phage under simulated infection conditions. BMC Microbiology 2010, 10:301 doi:10.1186/1471-2180-10-301

L. Kvachadze et al.: Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens. Microbial Biotechnol. (2011) 4(5), 643-650

Media information:

You will find this press release on our web site at www.dsmz.de.

Press officer:

Susanne Thiele
Head of Public Relations
Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures
Inhoffenstrasse 7 B
38124 Braunschweig
Germany
Phone ++49531-2616-300
Fax ++49531-2616-418
susanne.thiele@dsmz.de

About the Leibniz Institute DSMZ

The Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures GmbH is a Leibniz Association institution. Offering comprehensive scientific services and a wide range of biological materials, it has been a partner for research and industry organizations worldwide for decades. DSMZ is one of the largest biological resource centers of its kind to be compliant with the internationally recognized quality norm ISO 9001:2008. As a patent depository, DSMZ currently offers the only option in Germany of accepting biological materials according to the requirements of the Budapest Treaty. The second major function of DSMZ, in addition to its scientific services, is its collection-related research. The Brunswick (Braunschweig), Germany, based collection has existed for 44 years and holds more than 49,000 cultures and biomaterials. DSMZ hosts the most diverse collection worldwide: In addition to fungi, yeasts, bacteria, and archaea, it is home to human and animal cell cultures, plant viruses, and plant cell cultures that are archived and studied there. www.dsmz.de

Leibniz Association
The Leibniz Association connects 89 independent research institutions that range in focus from the natural, engineering and environmental sciences via economics, spatial and social sciences to the humanities. Leibniz institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz institutions collaborate intensively with universities – in the form of “WissenschaftsCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad. They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the importance of these institutions for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 16,500 individuals, including 7,700 researchers. The entire budget of all the institutes is approximately 1.4 billion EUR.

Weitere Informationen:

http://www.dsmz.de

Susanne Thiele | idw - Informationsdienst Wissenschaft

Further reports about: DSMZ Pirates antibiotics bacteria bacterial cystic fibrosis pathogens targeting therapeutic

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>