Ecological strategies to end the war on resistance

Military metaphors are pervasive in the language of antibiotics and resistance 1 .Bacterial pathogens are foreign invaders with whom we're at war.To fight them we deploy antibiotic chemical weapons.Powerful antibiotics are big guns, narrow-spectrum antibiotics are silver bullets, and broad-spectrum antibiotics are nuclear bombs.We're in a losing battle against antibiotic-resistant superbugs, and quickly running out of ammunition.Metaphors shape how you feel about an issue, and how you feel often determines the actions you take.Framing resistant bacteria as foes to be feared traps us within a fundamentally adversarial us-versus-them framework, where the only possible outcomes are their eradication-or ours.Instead, a growing body of research is re-examining antibiotic resistance through the lens of microbial ecology and evolution.This work has revealed that bacterial resistance significantly predates human use of modern antibiotics, with resistance genes encoded by many benign environmental and commensal microbes often before they are detected in pathogens 2 .Unchecked antibiotic use can dramatically amplify these resistance reservoirs, select for their dissemination into pathogens, and engender significant negative side effects on human health 3,4 .Given the dwindling approval of new antibiotics 5 , we must rethink the brute force approaches that attempt (futilely) to fight resistance by searching for the next bacteria-killing molecule.Instead, we should pursue complementary strategies that mitigate selection of antibiotic resistance by improving stewardship and developing novel chemotherapeutic, probiotic, and prebiotic strategies for suppressing bacterial virulence and supporting commensalism.To contrast the military metaphors, we metaphorize these ecological approaches using the diplomatic terms of: disarmament, non-proliferation, and soft power.Strategies for targeted killing of pathogens must invariably remain part of our medical toolkit, but by pursuing these complementary strategies, we argue that we can better foster sustainable co-existence with our microbial co-habitants and tip the scales against pathogenesis.