Collection 

Antimicrobial Resistance

Resistance to antimicrobials is a global problem of increasing importance. Pathogens rapidly develop mutations that render current treatments ineffective. For example, resistance to carbapenems, one of the ‘last lines’ of antibiotics, is widespread and has been observed in numerous countries; resistance to artemisinin, the gold standard in malaria treatment, has also emerged. Our current arsenal of antimicrobial agents thus has a limited lifespan and new drugs are urgently needed. Tackling this resistance will require a deep understanding of microbial infections and the mechanisms through which resistance arises, as well as concerted efforts between academia and industry aimed at developing novel antimicrobial agents.

The content for this site has been chosen by the editors of several Nature journals and the collection of review articles have been made freely available for 6 months, thanks to support from Merck & Co., Inc., Kenilworth, NJ, USA. The editors have also selected a wide range of additional and related content to supplement the collection and provide a comprehensive resource on antimicrobial resistance.

This collection has been produced with support from Merck & Co., Inc., Kenilworth, NJ, USA. As always, Nature Publishing Group retains sole responsibility for all editorial content.

Image © Philip Patenall, Nature Research Group

Diverse microorganisms and drugs

Protocols

The culture of pathogens and generation of appropriate models is crucial to the study of antimicrobial resistance. Nature Protocols publishes peer-reviewed protocols containing recipe-style details to facilitate implementation of the latest methods.

Building a morbidostat: an automated continuous-culture device for studying bacterial drug resistance under dynamically sustained drug inhibition

Erdal Toprak, Adrian Veres, Sadik Yildiz, Juan M Pedraza, Remy Chait, Johan Paulsson & Roy Kishony

We present a protocol for building and operating an automated fluidic system for continuous culture that we call the 'morbidostat'. The morbidostat is used to follow the evolution of microbial drug resistance in real time.

In vitro and in vivo generation and characterization of Pseudomonas aeruginosa biofilm–dispersed cells via c-di-GMP manipulation

Song Lin Chua, Louise D Hultqvist, Mingjun Yuan, Morten Rybtke, Thomas E Nielsen, Michael Givskov, Tim Tolker-Nielsen & Liang Yang

Here we present in vitro and in vivo protocols for the generation and characterization of dispersed cells from Pseudomonas aeruginosa biofilms by reducing the intracellular c-di-GMP content through modulation of phosphodiesterases (PDEs). Unlike conventional protocols that demonstrate biofilm dispersal by biomass quantification, our protocols enable physiological characterization of the dispersed cells. Biomarkers of dispersed cells are identified and quantified, serving as potential targets for treating the dispersed cells. The in vitro protocol can be completed within 4 d, whereas the in vivo protocol requires 7 d.

Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances

Irith Wiegand, Kai Hilpert & Robert E. W. Hancock

The aim of broth and agar dilution methods is to determine the lowest concentration of the assayed antimicrobial agent (minimal inhibitory concentration, MIC) that, under defined test conditions, inhibits the visible growth of the bacterium being investigated. MIC values are used to determine susceptibilities of bacteria to drugs and also to evaluate the activity of new antimicrobial agents.