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What counters antibiotic resistance in nature?
Remy Chait, Kalin Vetsigian & Roy Kishony
Antibiotics promote the spread of resistance in the clinic, but various mechanisms may exist in natural environments that tilt the balance toward antibiotic sensitivity. Studying such mechanisms could help us understand the evolutionary dynamics of resistance and sensitivity in the wild, which may inspire new therapeutic strategies.
Antibiotics, which permit the eective treatment of bacterial infections, represent a fundamental
triumph of medical science. However, their widespread clinical and agricultural use has led to the rapid emergence and spread of resistance. This proliferation of resistance reduces or eliminates the utility of antibiotics, rendering some clinical infections dangerously untreatable1.
In light of the slow rate of discovery of new drugs, reducing the rate at which resistance evolves oers a tenable strategy for maintaining the efficacy of existing and future antibiotics1,2.
To gain some insight into mechanisms that can keep antibiotic resistance in check, it is interesting to consider an evolutionary-ecological perspective. Most clinical antibiotics are derivatives of natural microbial products that evolved long before the era of medicinal antibiotic use and are commonly found in the chemical repertoire of soil microbes35.
Resistance to these compounds evolvedin the natural environment long ago,and in fact the resistance genes we see in the clinic today oen bear similarity to genes in the environment3,6,7. Althoughthe compounds and the resistance genes are similar in these two contexts, their dynamics are profoundly dierent. Whereas clinical resistance tends to increase substantially with time, resistant and sensitive bacteria have presumably existed together in soil environments for much longer periods (Fig. 1). Why is it that resistant bacteria do not take over in the soil environment? What mechanisms might be acting in nature to keep antibiotic resistance in check? We discuss several aspects of the soil environment thatcould explain why antibiotic resistance does not take over, including antibiotic
combinations, compounds that inhibit or toxify resistance, degradation products of antibiotics and other ecological roles of antibiotics.
Antibiotic combinations
One striking dierence between the clinical and soil environments is that microbes in the clinical context are exposed to one (or few) drugs at a time, whereas those in a soil environment are likely to encounter many more toxins simultaneously. Can the mere presence of...