Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New insights into insect antimicrobials point the way to novel antibiotics

09.08.2002


The emergence of antibiotic-resistant strains of bacteria has become a serious public-health concern, and, accordingly, scientists are investigating new classes of antimicrobials for their efficacy against disease-causing bacteria. One developing area of study involves antimicrobial peptides derived from insects. Recent studies have identified the protein target in bacteria of these antimicrobial peptides and suggested that the peptides are not toxic to mammalian cells including those of humans, raising the possibility that they could someday be used to develop new antibiotic drugs.

Now, in a new study of an insect-derived antimicrobial peptide called pyrrhocoricin, scientists at The Wistar Institute have identified which segments of the peptide are necessary for the killing of bacteria and which segments are involved in bacterial and mammalian cell entry. The Wistar scientists further confirmed that this antimicrobial peptide must bind to the previously identified intracellular bacterial protein target in order to kill bacteria. The research team also identified a possible binding site for the antimicrobial peptide on the target bacterial protein for the first time.

Because the stretches of the peptide that are responsible for cell entry are separate from the segments responsible for bacteria killing, the research team says that it might be possible to use an altered version of the peptide as a delivery vehicle for a variety of drugs into human cells, rather than solely as an antimicrobial. The results are published online today in the European Journal of Biochemistry.



"This study lays the groundwork for the design of a novel family of antimicrobials," says Laszlo Otvos Jr., Ph.D., associate professor at The Wistar Institute and senior author of the study. "It also suggests that these peptides could be used as a universal drug delivery vehicle, whether for new drugs or to improve the delivery of existing peptide-based drugs."

The antimicrobial peptide kills bacteria by binding to a protein target called DnaK. DnaK is a special type of protein called a heat-shock protein, responsible for correcting misshapen proteins. When the antimicrobial peptide binds to DnaK, it prevents DnaK from doing its protein-repair work, killing the bacteria.The Wistar research team studied the binding of engineered analogs of pyrrhocoricin to a series of bacterial strains. As they anticipated based on their previous investigations, they found a complete correlation between the peptide binding to a small fragment of bacterial DnaK and bacteria killing. The researchers also confirmed that the peptide does not bind to the mouse or human protein equivalents to DnaK, further suggesting that the peptide would not be toxic to mammals.

The investigators identified a possible binding surface for the antimicrobial peptide on an E. coli DnaK fragment. Knowledge of this binding site could lead to the development of new drugs tailored to combat E. coli. It may also be possible to develop drugs that would kill bacteria that are unresponsive to native pyrrhocoricin, but for which the DnaK structure is known.

In related ongoing studies, Otvos and his team have shown that analogs of pyrrhocoricin are able to kill clinical strains of resistant bacteria that cause urinary, gastrointestinal and respiratory-tract infections. In a mouse H. influenzae lung infection model, the researchers have shown that a pyrrhocoricin analog can dramatically reduce bacterial counts in the lungs and be administered in a non-invasive way. These studies are demonstrating that engineered antibacterial peptides can be used in a clinical setting against bacteria with resistance to existing antibiotics.


In addition to senior author Otvos, the lead author of the study is Goran Kragol, Ph.D., and co-authors are Michael A. Chattergoon, B.S., Mare Cudic, Ph.D., Barry A. Condie, B.S., and associate professor Luis J. Montaner, D.V.M., D.Phil., all of The Wistar Institute. Additional co-authors are Ralf Hoffmann, Ph.D., of Heinrich-Heine-Universität, Sandor Lovas, Ph.D., of Creighton University, Philippe Bulet, Ph.D., of Institut de Biologie Moleculaire et Cellulaire, and K. Johan Rosengren, Ph.D., of the University of Queensland.

The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Cente- one of only eight focused on basic research. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.

Marion Wyce | EurekAlert!
Further information:
http://www.wistar.upenn.edu),

More articles from Health and Medicine:

nachricht New nanomedicine slips through the cracks
24.04.2019 | University of Tokyo

nachricht Sugar entering the brain during septic shock causes memory loss
23.04.2019 | Rensselaer Polytechnic Institute

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: Energy-saving new LED phosphor

The human eye is particularly sensitive to green, but less sensitive to blue and red. Chemists led by Hubert Huppertz at the University of Innsbruck have now developed a new red phosphor whose light is well perceived by the eye. This increases the light yield of white LEDs by around one sixth, which can significantly improve the energy efficiency of lighting systems.

Light emitting diodes or LEDs are only able to produce light of a certain colour. However, white light can be created using different colour mixing processes.

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

Proteins stand up to nerve cell regression

24.04.2019 | Life Sciences

New sensor detects rare metals used in smartphones

24.04.2019 | Life Sciences

Controlling instabilities gives closer look at chemistry from hypersonic vehicles

24.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>