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antibiotics in nature

Last year's Schol Bio paper had a question about allelopathy. The context centred on Black Walnuts (Juglans nigra). These are large deciduous trees with an extensive root system - and they release an allelopathic chemical called juglone, which has a number of toxic effects on a range of other plant species. This ability to kill or weaken potential competitors is a significant advantage to J.nigra as it improves the survival of walnut seedlings, and reduces competition for resources such as water, light, and nutrients. 

Such allelopathic chemicals are relatively widespread in nature, although we may give them different names depending on the organism producing them. For example, the chemicals produced by fungi to inhibit bacterial growth are called antibiotics (some of which are the basis of many modern antibiotic treatments for infection - 'penicillin' was just the first of these). Similarly some bacteria produce substances that kill off fungi. The term 'antibiotic' was first coined to describe streptomycin, originally isolated from an organism called Streptomyces. (As an example of how science moves along: Streptomyces belongs to a group of microbes called actinomycetes. The suffix -myces suggests they are fungi, & in fact that's how they were described when I first encountered them. However, they're now classified as prokaryotes, along with other bacteria.)

For a long time we've regarded these allelopathic chemicals as a form of biological warfare, produced by one species to kill off or deter competitors. So I was intrigued to read an article (Mlot, 2009) that suggested that they could have other, quite different functions in the microbial world.

Streptomycin works against the bacteria that cause tuberculosis by binding to their ribosomes & preventing protein synthesis. This mode of action has led some researchers to suggest that this & similar molecules are particularly ancient: hangovers from the 'RNA world' that may have preceded the evolution of cellular life & now co-opted into other roles. Certainly it seems that some microbe genomes code for an awful lot of apparent antibiotic compounds: more than 25 in some cases. What's more, we use these compounds - produced largely by microbes living in the soil - against organisms that are pathogenic on animals. These are not exactly groups that would normally encouter each other on a regular basis. So why do organisms like the actinomycetes invest so much energy in producing their small 'antibiotic' molecules, if they're not used in killing off competitors?

While scientists have studied how antibiotics work in bacterial & fungal cultures in the laboratory, this is a far cry from what may be happening in natural microbial communities. While in some cases the molecules do work in an allelopathic way, in others there seems to be something else going on - not least because the purported antibiotic molecules are not being produced in the high concentrations needed to kill other cells. And dose (concentration) does matter.

Recent research has shown that in low concentrations, substances such as erythromycin seem to influence expression of a whole range of microbial genes by interacting with their promoters, & so affect many different cellular activities. Scientists suggest that at these low concentrations the molecules are involved in chemical communication between cells. For example, the antifungal antibiotic nystatin prompts Bacillus subtilis to make a glycoprotein that lets them stick together, forming something known as a biofilm. It does this by causing a rapid outflow of potassium ions from the cells (something that also happens when a nerve impulse is being transmitted along a neuron), which some in the field see as evidence for the communication hypothesis.

Interestingly, this may also explain why the genes that confer antibiotic resistance to things like the 'superbug' MRSA are also foudn in some soil microbes that haven't been anywhere near a supply of pharmaceutical drugs. Could they also function in this cell-to-cell communication? And if so, is there some way that we can put them to good use in our own on-going fight against disease?

C.Mlot (2009) Antibiotics in nature: beyond biological warfare. Science 324: 1637-1639 

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