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Routes of Resistance

Our focus on using antibiotics to kill bacteria has blinded us to their diverse functions in the organisms that make these chemicals

Robert L. Dorit

Rethinking the Fight

We cannot lose sight of how profoundly 50 million pounds of annual antibiotic use impacts the microbial world. The widespread use of antibiotics has created a black market for antibiotic resistance mechanisms where bacteria poach ready-made shortcuts to resistance: It has enhanced and rewarded the evolution of a vast network that allows for the transfer of resistance along nongenealogical lines. These mechanisms of horizontal transfer now connect the extensive environmental resistome with any pathogen (or commensal bacterium) exposed to clinical concentrations of antibiotic. As a result, bacteria in the presence of potentially lethal concentrations of antibiotics no longer face the daunting evolutionary challenge of remaining alive while they and their descendants cobble together resistance one point mutation at a time. Instead, fully functional resistance located on moveable genetic elements can now be acquired by swapping with other bacteria, or by taking such elements up directly from the environment.

To make matters more challenging, many of these ready-made resistance elements are packaged as a set. Multiple genes encoding resistance to multiple antibiotics now travel as a team (up to 74 different resistances have been found to occur together). The ubiquitous presence of human-administered antibiotics in the environment selects strongly for bacteria that are able to acquire these resistance packs, and may also be selecting for the evolution of increasingly mobile and promiscuous elements equipped with increasingly diverse arrays of resistances. As mobile elements, their Darwinian imperative is to make and move copies of themselves, and that in turn may depend on their ability to keep their host bacteria alive in a sea of antibiotics.

Many forces—social, economic and medical—propel excessive antibiotic use. An expanded perspective on the role of antibiotics and resistance in no way contradicts the urgent need to reduce antibiotic consumption. Our current behavior, moreover, drowns out the subtle melody unfolding in microbial ecosystems and superimposes the deafening roar of therapeutic antibiotics and increasingly resistant pathogens in its place. We can hope that new antibiotics will continue to be developed and broadly prescribed, buying us a few more years. We can keep doing what we have always done, and hope we can reach a stalemate with ever more-aggressive bacterial pathogens. Or we can instead start paying more attention to what microbial ecosystems have to teach us, acknowledging the lessons that have always been embedded in a gram of soil. Our relationship to the unseen world extends far beyond pathogens and our efforts to combat them. We can, if we put our minds to it, begin to see a world in a grain of sand.

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