Selection of Resistance By Very Low Levels of Antibiotics

What are the origins of the antibiotic resistance problem? Each year many tons of antibiotics are used in medicine, and after passing through the human body much of it enters the wider environment in an active form via sewage and treatment plants. Even more antibiotics enter the environment from uses outside of human medicine, for example via agriculture and aquaculture. The result is a worldwide environmental pollution by antibiotics that could potentially select resistant bacterial pathogens. Environmental concentrations of antibiotics vary widely, from very low levels in pristine environments, up to extremely high levels, for example in rivers downstream of pharmaceutical production facilities. We have shown experimentally that very low levels of antibiotics, similar to the concentrations found in many environments, can select and enrich for resistant mutant bacteria. In addition, other environmental contaminants like heavy metals select indirectly for antibiotic resistance because these genes are often carried and transferred together.

Environmental selection of resistant bacteria by low levels of antibiotic pollution causes two major problems. The first is the obvious one, that there is probably a lot of selection for resistance happening worldwide. The second problem is that the selection of resistance by low levels of antibiotics specifically selects for bacteria that develop resistance without losing fitness. This is a very serious consequence because it means that even if we were to succeed in implementing policies to reduce future environmental pollution by antibiotics, the resistant bacteria would likely remain in the environment because there would be little or no counter-selection to remove them. This pessimistic prognosis supports the need to develop new drugs and strategies to deal with bacterial infections (new antibiotics, other classes of antibacterial drugs, alternative approaches, etc). However, it also emphasises the need to implement policies worldwide on the use and release of any novel drugs, to ensure that we do not repeat the present failure with the hard-won new drugs that will hopefully be introduced into medicine to fight infections. This understanding of the nature and consequences of resistance selection provides a scientific basis for developing strategies to address the resistance problem.