Antibiotic resistance: from Darwin to Lederberg to Keynes

Microb Drug Resist. 2013 Apr;19(2):73-87. doi: 10.1089/mdr.2012.0115. Epub 2012 Oct 9.

Abstract

The emergence and spread of antibiotic-resistant bacteria reflects both, a gradual, completely Darwinian evolution, which mostly yields slight decreases in antibiotic susceptibility, along with phenotypes that are not precisely characterized as "resistance"; and sudden changes, from full susceptibility to full resistance, which are driven by a vast array of horizontal gene transfer mechanisms. Antibiotics select for more than just antibiotic resistance (i.e., increased virulence and enhanced gene exchange abilities); and many non-antibiotic agents or conditions select for or maintain antibiotic resistance traits as a result of a complex network of underlying and often overlapping mechanisms. Thus, the development of new antibiotics and thoughtful, integrated anti-infective strategies is needed to address the immediate and long-term threat of antibiotic resistance. Since the biology of resistance is complex, these new drugs and strategies will not come from free-market forces, or from "incentives" for pharmaceutical companies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / drug therapy
  • Bacterial Infections / microbiology
  • Biological Evolution
  • DNA Transposable Elements
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Gene Transfer, Horizontal
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / genetics*
  • Gram-Negative Bacteria / metabolism
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / genetics*
  • Gram-Positive Bacteria / metabolism
  • Humans
  • Selection, Genetic / drug effects
  • Selection, Genetic / genetics

Substances

  • Anti-Bacterial Agents
  • DNA Transposable Elements