To highlight the problem of resistance to antimicrobials, Nature Reviews Microbiology presents a set of specially commissioned articles that focus on key issues in the field, including the role of antibiotic resistance in nature, how the spread of antimicrobial resistance could be limited and the pharmaceutical strategies that are used to overcome resistance to various classes of antimicrobials. The Focus issue is accompanied by a joint Web Focus with Nature Reviews Drug Discovery.


Editorial

A step in the right direction

doi:10.1038/nrmicro2345

Nature Reviews Microbiology 8, 244 (2010)

Fighting infectious diseases in developing countries is difficult owing to limited financial resources. Many pharmaceutical companies have programmes that provide much needed medicines, but more can be done.

Research highlight

Antimicrobials: Reactive resistance

doi:10.1038/nrmicro2344

Nature Reviews Microbiology 8, 248 (2010)

Sublethal concentrations of bactericidal antibiotics can generate multidrug resistance through an increase in the mutation rate that is driven by the formation of reactive oxygen species.

Reviews

Antibiotic resistance and its cost: is it possible to reverse resistance?

Dan I. Andersson & Diarmaid Hughes

doi:10.1038/nrmicro2319

Nature Reviews Microbiology 8, 260-271 (2010)

The mutations that confer antibiotic resistance lead, in most cases, to a decrease in fitness. Here, Andersson and Hughes describe the various ways in which bacteria can minimize the fitness cost and how this may be exploited to reverse antibiotic resistance.

Call of the wild: antibiotic resistance genes in natural environments

Heather K. Allen, Justin Donato, Helena Huimi Wang, Karen A. Cloud-Hansen, Julian Davies & Jo Handelsman

doi:10.1038/nrmicro2312

Nature Reviews Microbiology 8, 251-259 (2010)

Antibiotic resistance seriously threatens our ability to treat infectious diseases. The genes conferring resistance can easily move between organisms, resulting in nearly untreatable diseases. Jo Handelsman and colleagues describe how resistance is spread, the origin of the genes conferring this resistance and the roles they may have in their natural environments.

Artemisinin resistance: current status and scenarios for containment

Arjen M. Dondorp, Shunmay Yeung, Lisa White, Chea Nguon, Nicholas P.J. Day, Duong Socheat & Lorenz von Seidlein

doi:10.1038/nrmicro2331

Nature Reviews Microbiology 8, 272-280 (2010)

Artemisinin is one of the few antimalarials for which there is no widespread resistance. However, malaria parasites with decreased sensitivity have been reported recently. In this Review Arjen Dondorp and colleagues describe the initial detection of artemisinin resistance and discuss several strategies to prevent its spread.

Resistance to and synthesis of the antibiotic mupirocin

Christopher M. Thomas, Joanne Hothersall, Christine L. Willis & Thomas J. Simpson

doi:10.1038/nrmicro2278

Nature Reviews Microbiology 8, 281-289 (2010)

Mupirocin is a polyketide antibiotic produced by Pseudomonas fluorescens that is used to control the carriage of methicillin-resistant Staphylococcus aureus. Here, Thomas and colleagues describe the mechanisms underlying the mode of action and biosynthesis of mupirocin and discuss how this understanding could lead to the development of novel antibiotics.

Anti-virulence strategies to combat bacteria-mediated disease

David A. Rasko & Vanessa Sperandio

doi:10.1038/nrd3013

Nature Reviews Drug Discovery 9, 117-128 (2010)

The growing prevalence of multidrug-resistant bacterial strains, together with the decline in the discovery of novel antibacterial agents, has made the effective treatment of many bacterial infections increasingly difficult. Here, Rasko and Sperandio review bacterial virulence mechanisms and discuss the potential of emerging anti-virulence therapeutic strategies.

New medicines to improve control and contribute to the eradication of malaria

Timothy N. C. Wells, Pedro L. Alonso & Winston E. Gutteridge

doi:10.1038/nrd2972

Nature Reviews Drug Discovery 8, 879-891 (2009)

The recent call for the eradication of malaria has sparked the development of new drug classes with improved product profiles. Wells and colleagues review the currently available antimalarials and their limitations, the contribution of genome-based technologies and in vitro screening of whole parasites to the discovery of new targets, and the issues that should be considered when developing such antimalarials.

A pre-emptive strike against malaria's stealthy hepatic forms

Dominique Mazier, Laurent Rénia & Georges Snounou

doi:10.1038/nrd2960

Nature Reviews Drug Discovery 8, 854-864 (2009)

The emerging resistance to current antimalarial drugs calls for new strategies to control the disease. This article highlights the potential of targeting the obligate short-lived hepatic forms of the malaria parasite and ways to overcome the challenges of developing drugs that will achieve this.

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