Features | Partner Sites | Information | LinkXpress
Sign In
Demo Company

Synthetic Antibiotic Kills Bacteria and Prevents Biofilm Formation

By BiotechDaily International staff writers
Posted on 14 Nov 2013
Image: Scanning electron micrograph of Gram-negative bacteria. In recent years, the efficacy of antibiotics has been drastically reduced due to increasing bacterial resistance (Photo courtesy of the University of Copenhagen).
Image: Scanning electron micrograph of Gram-negative bacteria. In recent years, the efficacy of antibiotics has been drastically reduced due to increasing bacterial resistance (Photo courtesy of the University of Copenhagen).
The peptidomimetic compound HDM-4 (Host Defence Peptidomimetic 4) exhibits broad-spectrum antibacterial activity against Gram-negative bacteria and inhibits the formation of biofilms.

A peptidomimetic is a small protein-like molecular chain designed to mimic a peptide. They typically arise either from modification of an existing peptide, or by designing similar systems that mimic peptides, such as peptoids and beta-peptides. The altered chemical structure is designed to favor molecular properties increasing stability or biological activity. These modifications involve changes to the peptide that will not occur naturally (such as altered backbones or the incorporation of non-natural amino acids).

Investigators at the University of Copenhagen (Denmark) and their colleagues at the University of British Columbia (Canada) recently characterized HDM-4's mode of action against Gram-negative bacteria.

They reported in the October 10, 2013, issue of the journal Chemistry & Biology that HDM-4 generated holes in the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentration (MIC). In addition, HDM-4 rapidly became distributed within the bacterial cell at lethal concentrations that could bind to DNA.

The multimodal action of HDM-4 resulted in it being less likely to lead to resistance development as compared to single-target antibiotics. The compound exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the host's immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. Additionally, the compound suppressed lipopolysaccharide-mediated inflammation by reducing the release of the proinflammatory cytokines IL-6 and tumor necrosis factor-alpha (TNF-alpha).

“We have succeeded in preparing and characterizing a very stable substance that kills multiresistant bacteria extremely quickly and effectively. The most interesting aspect is that the bacteria are attacked using a multifunctional mechanism that drastically reduces the risk of resistance development compared with traditional antibiotics,” said first author Dr. Rasmus Jahnsen, a researcher on drug design and pharmacology at the University of Copenhagen. “The killing mechanism involves destabilizing the bacterial membrane and binding onto the bacteria’s DNA, which in both cases results in the death of the bacteria. We have also shown that the substance can activate the human body’s own immune cells, strengthening its defense against bacteria during infection.”

“Only a tiny fraction of pharmaceutical research is devoted to development of new antibiotics — partly because research into cancer and chronic diseases such as diabetes and cardiovascular diseases are seen as better long-term investments. This leaves us in the extremely unfortunate situation where infectious diseases once again pose extremely serious threats to human health as the efficacy of medical drugs continues to be undermined by bacterial resistance. It is therefore important to conduct more research into new antibiotics,” said Dr. Jahnsen.

Related Links:

University of Copenhagen
University of British Columbia



view channel
Image: Micrograph showing immunofluorescence of skin differentiation markers for basal keratinocytes (Photo courtesy of Dr. Russ Carstens, University of Pennsylvania).

Alternate Splicing Proteins Critically Linked to Skin and Organ Development

Two proteins that regulate alternative splicing in epithelial cells have been linked to the proper development of the skin and protective layers that surround other organs in the body. Two steps are... Read more

Lab Technologies

view channel

New Genomic Research Kit Simplifies Exome Studies

An exciting new tool is now available for biotech researchers working in the field of genomic analysis. The human exome is critical to our genetic make-up and is generally accepted as having the greatest influence on how the genetic blueprint is utilized. The exome is defined as all coding exons in the genome and is... Read more


view channel

Collaboration Agreement to Boost Discovery of Fully Human Antibodies for Therapeutic Use

The discovery of fully human antibodies for therapeutic use will be boosted by a recently announced collaboration between a major university research center and a dynamic biopharmaceutical development company. Regeneron Pharmaceuticals, Inc. (Tarrytown, New York, USA) and The Experimental Therapeutics Institute (ETI)... Read more


17 Oct 2015 - 21 Oct 2015
25 Oct 2015 - 29 Oct 2015
16 Nov 2015 - 19 Nov 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.