25-Apr-2022 - University of Wisconsin-Madison

New Tools Against Hospital Infections?

Encapsulated peptide blocks communication and virulence of resistant Staphylococcus

Antibiotic-resistant hospital pathogens are not to be underestimated as a health risk. A research team has now introduced a new approach for treating multiple-drug resistant Staphylococcus in the journal Angewandte Chemie. It is based on a synthetic peptide that reduces the virulence of the bacteria by blocking their communication by “quorum sensing”. Controlled release of the drug from degradable microparticles very strongly inhibited skin wound infections in an animal model.

The hospital is a place where we are supposed to get healthy, not be made sicker by a dreaded hospital infection. Pathogens that are often harmless to healthy people can become very dangerous when they enter the bodies of weakened patients, for example through surgical wounds or internal examinations. Alarm bells really start to ring in cases of multidrug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), for which almost no antibiotic is effective. In the USA, about 100,000 hospital infections and almost 20,000 deaths are attributed to this bacterium.

The more antibiotics, the more resistance. The upcoming antibiotics crisis can only be overcome through alternative approaches. “Anti-virulence” strategies thus aim to reduce the infectiousness of the pathogen without killing it off. This reduces the selective pressure that leads to the development of resistance. Because the severity of the infection is reduced, ideally the patient’s immune system can fight off the infection.

As their point of attack, the interdisciplinary team working with Helen E. Blackwell at the University of Wisconsin chose a chemical communication system used by bacteria to communicate with each other, called quorum sensing (QS). Many bacteria use QS to regulate the production of virulence factors, or toxins, involved in infections. Among other things, virulence factors give pathogens the ability to attach to host cells and enter them.

S .aureus and related bacteria have a QS circuit based on the “accessory gene regulator” (agr) system. The QS signal molecule is called the “autoinducing peptide” (AIP). The research team developed a synthetic peptide similar to AIP that blocks the agr system with unusual effectiveness, also blocking QS. Omitting an end part of the peptide chain significantly slowed the degradation of the inhibitor peptide in tissue. Encapsulation of the inhibitor in biodegradable polymer particles allowed for delayed release, prolonging the period of activity—making high effectiveness at a low dose possible. In a mouse model for skin abscess, infections with S. aureus could be almost completely blocked by a local injection of the encapsulated peptide.

This new inhibitor peptide could provide an approach to therapeutic strategies for fighting bacterial infections and may provide new insights into the role of agr and QS in chronic infections. In addition, it could be the foundation for the development of coatings that block bacterial infections for applications like implants.

Facts, background information, dossiers

  • antibiotic resistance
  • hospital germs
  • multidrug resistance
  • Staphylococcus
  • Methicillin-resista…
  • antibiotics
  • bacteria
  • quorum sensing
  • virulence factors

More about University of Wisconsin-Madison

More about Angewandte Chemie

  • News

    Firefly Luminescence Reveals Pesticides

    A luminescence reaction modeled on fireflies can detect contamination with organophosphates with high sensitivity, ease, and low cost. At the center of this technology is a new enzymatic method for the synthesis of analogues of luciferin, the substance that makes fireflies glow. As reported ... more

    Strong and elastic, yet degradable: protein-based bioplastics

    More than eight million tons of plastic end up in the oceans every year—a serious danger for the environment and health. Biodegradable bioplastics could provide an alternative. In the journal Angewandte Chemie, a research team has now introduced a new method for the production of protein-ba ... more

    Healing Nerves on Spider Silk

    Spider silk has enormous potential in regenerative medicine thanks to being a natural fiber that is tough, stable, and biodegradable. Researchers have now produced double-sided spider silk fibers, which could provide damaged nerve or muscle cells with a platform for growth. As the researche ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: