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 Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children'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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>