Biomimicry Institute - Red Seaweed Inspired Antibiotics

Red Seaweed Inspired Antibiotics

Learning from Seaweed to Repel Bacteria without Creating Resistance

Red seaweed (Delisea pulchra), shown here off the coast of Australia, repels bacteria successfully through disrupting their communication rather than killing them. Emulating such methods in the creation of antibiotics would minimize bacterial resistance and impacts to non-target organisms. BioSignal Ltd. has synthesized the signal-jamming furanone molecules that this species uses to repel bacteria, and is pursuing their application in a number of health and technology applications. Photo courtesy of the Centre for Marine Bio-Innovation.

The discovery a few decades ago that bacteria use chemicals to communicate with each other, coordinate their behavior, and alter the activity of their genes in response to density has completely transformed our previous conception of these creatures as relatively simple and isolated organisms. Using signaling molecules called autoinducers, bacteria finding a suitable habitat or host communicate this fact to other bacteria in the vicinity. These bacteria respond by both converging on the habitat or host and producing more signaling molecules, creating a positive feedback loop. Through this process, known as "quorum sensing", bacteria form bacterial colonies or "biofilms". Sensing the relative density of other bacteria through the concentration of autoinducers, bacteria then transform their physical and biochemical behavior as signaling molecule concentration triggers gene expression changes. Bacteria that are benign as individuals, reorganized into biofilms, then begin to pump out the defensive toxic chemicals that result in a multitude of diseases in humans and agricultural plants to the rupture of oceanic oil pipelines. At the same time, the biocidal antibiotics human conventionally rely upon to combat bacteria are becoming increasingly ineffective as the small percentage of surviving bacteria commonly reproduce into antibiotic resistant strains in response to this evolutionary "arms race".

Peter Steinberg, a marine ecologist at the University of New South Wales, noticed while diving in the ocean one day that a particular species of seaweed, Delisea pulchra, was conspicuously free of the biofilms so common on the other species around it. This led him to investigate the surface chemistry of the seaweed, and, to the discovery of a group of chemicals the seaweed produced called furanones which somehow prevented biofilm formation. Dr. Steinberg went on to synthesize the furanones, and one day showed his colleague, microbiologist Staffan Kjelleberg, a molecular diagram of the furanone chemicals he was in the process of patenting. Staffan looked at Peter and asked him what bacterium had produced the chemical. Peter explained that it actually wasn't produced by bacteria, but by a seaweed. Staffan replied that the chemicals Peter had synthesized looked, curiously enough, a great deal like bacterial signaling molecules. At that moment, both men realized that red seaweed had found an entirely novel way of repelling bacteria - not by killing them as human-made antibiotics typically do, but by disrupting their ability to communicate.

How It Works
In order for quorum sensing to occur, many species of bacteria use signaling molecules known as autoinducers or ‘AHL' (N-acyl homoserine lactone). The furanones produced by Delisea pulchra are similar enough to AHL signaling molecules to bind readily to the specific protein-covered receptor sites on bacteria that sense these molecules. Once attached, these furanones physically block autoinducer signaling molecules from attaching to passing bacteria, effectively coating the receptor organs of bacteria in order to make them deaf. However, the furanones are different enough from AHL signaling molecules that they do not themselves trigger the production of more autoinducers or changes in a bacterium's expression of genes. In fact, while attached, furanones actively break down the proteins covering the bacteria's reception site, temporarily impairing the bacteria's ability to receive signals at all. This method effectively prevents bacteria from forming groups and becoming virulent, but without physically killing them.

Why It Matters
We tend to think of bacteria as a disagreeable element of life on Earth, but in fact, the vast majority of bacteria species are either helpful or harmless to people. Indeed, without bacteria, humans would neither survive nor have ever come into existence at all. The origin of bacteria stretches back billions of years, and over this time period they have formed intricate symbiotic relationships with the rest of life. The cells of our bodies, for example, each contain elements derived from bacteria which entered eukaryotic cells billions of years ago, and are now vital to our cells' operation. Millions of bacteria live in our intestines, helping us synthesize vitamins, process food which otherwise we could not digest, and competitively exclude potentially harmful bacteria. In addition, humans depend on bacteria in soil to fix atmospheric nitrogen into nitrogenous compounds, which the plants we depend upon require to grow.

At times, however, bacteria can be harmful, particularly when they form biofilms, causing debilitating or lethal human diseases such as cholera, cystic fibrosis, tetanus, diphtheria, typhoid, pneumonia, and tuberculosis. Indeed, over 80% of bacterial infections in humans are estimated to involve the formation of biofilms. Meanwhile, the antibiotics we use to eliminate harmful bacteria are increasingly ineffective, due to the rapid evolution in bacteria of antibiotic resistance. More than 70% of the bacterial infections people acquire in hospitals, for example, are now from bacteria exhibiting antibiotic resistance.

The antibiotic strategy of Delisea pulchra does not kill bacteria. The bacteria are only temporarily disabled in the presence of the seaweed and continue to reproduce normally. This greatly minimizes pressure for bacteria resistant to this seaweed's strategy to emerge through natural selection, a fact emphasized by the lack of such resistance after many millions of years of interaction between Delisea pulchra and potential bacterial pathogens. An additional advantage of this approach to antibiotics is that these furanones are specific to the bacteria being repelled, and do not harm non-target organisms as do biocidal treatments typically used to repel unwanted bacteria.

Antibiotic strategies which cause disruption in bacterial communication have huge potential application for improving human life in an environmentally sustainable manner. BioSignal Ltd. is now testing and/or already successfully applying synthetic furanones, based on those produced by Delisea pulchra, in a variety of applications including: medical treatment and devices; pipelines; heating, ventilating, and air conditioning systems; cleaning products; and water treatment.

Help Conserve These Inspiring Organisms!
Through the Biomimicry Institute's Innovation for Conservation Program, the organisms teaching us how to live sustainably on this planet receive our help conserving their habitats in return. After all, shouldn't we properly honor the organisms and ecosystems that evolved these ingenious, sustainable ideas, and thank them for showing us the way? Help us in our efforts to protect the habitats of these inspiring organisms!

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