Antibiotic Resistance

The Evolution of Antibiotic Resistance

Pathogenic bacteria resistant to many or all antibiotics already exist. Coupled with the rapid decline in microbiological research at pharmaceutical companies (and financial incentive elsewhere), the rapid rate at which resistance has evolved and spread has demanded a novel approach to addressing this critical human health issue. Here we propose a new paradigm in antibiotic discovery and development, one that applies ecological and evolutionary theory to design antimicrobial drugs that are more difficult and/or more costly for bacteria to resist. In essence, we propose to simply adopt the strategies invented and applied by bacteria for the past several billion years. Our research has revealed the manner in which bacteria create and deploy a powerful arsenal of biological weapons that maintain their efficacy for hundreds of millions of years.

We are also interested in understanding the source of the diversity of resistance determinants seen in clinical isolates of pathogenic bacteria. Numerous studies have suggested that these genes arise in a clinical setting in response to human-mediated antibiotic usage while more recent studies reveal that the environment can also serve as a reservoir for resistance determinants. Our approach here has been to investigate the relationship between environmentally- and clinically-derived resistance determinants by examining their molecular evolutionary history. Our research has revealed a vast reservoir of resistance genes in wild populations of bacteria while further phylogenetic analysis undercuts the notion of a separate reservoir of antibiotic resistance genes confined only to clinical settings. We have found, however, that strong levels of positive selection among antibiotic resistance genes (mutations that expand activity against multiple antibiotics) exist only in clinical populations. We argue that a more comprehensive exploration of the environmental reservoir is likely to shed light on the emergence and evolution of genes conferring resistance to antibiotics.

Resistance is Futile: the bacteriocin model for addressing the antibiotic resistance challenge

The Evolution of Reduced Microbial Killing

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