Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

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



Channels

Genomics/Proteomics

view channel
Image: Transmission electron micrograph of norovirus particles in feces (Photo courtesy of Wikimedia Commons).

Norovirus Interacts with Gut Bacteria to Establish a Persistent Infection That Can Be Blocked by Interferon Lambda

A team of molecular microbiologists and virologists has found that norovirus requires an intimate interaction with certain gut bacteria to establish a persistent infection, and that the infective process... Read more

Biochemistry

view channel
Image: Induced pluripotent stem (iPS) cells, which act very much like embryonic stem cells, are shown growing into heart cells (blue) and nerve cells (green) (Photo courtesy of Gladstone Institutes/Chris Goodfellow).

Methodology Devised to Improve Stem Cell Reprogramming

In a study that provides scientists with a critical new determination of stem cell development and its role in disease, researchers have established a first-of-its-kind approach that outlines the stages... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.