Reviews & Analysis

To survive in oxic environments, all organisms require mechanisms to degrade toxic reactive oxygen species (ROS). In this Review, James Imlay describes the oxidative stress response ofEscherichia coliand considers the damage caused by ROS and the adaptive strategies used by this bacterium to minimize intracellular ROS accumulation.

Recent studies have revealed a role for host translation inhibition in the innate immune surveillance and detection of bacterial pathogens. Lemaitre and Girardin review these findings and discuss whether translation inhibition is a direct innate immune signal or rather part of a more general metabolic stress response to infection.

The global rise of antibiotic resistance and the paucity of novel antimicrobial compounds in the pipeline have revived interest in the use of metals as antimicrobial agents. Here, Lemire, Harrison and Turner describe the principles of metal toxicity, the uptake of metals by microbial cells and the distinct types of cellular damage that they cause. They also discuss the use of metal-based agents as antimicrobials.

Helicobacter pyloriresides exclusively in the hostile environment of the stomach in approximately 50% of the human population and is a strong risk factor for cancer. Here, Salama, Hartung and Müller describe how this bacterium establishes persistent colonization through the interplay of virulence determinants and the subversion and manipulation of the host's immune response.

Although great progress has been made in the field of dengue research, there are still many unanswered questions concerning the interactions between dengue virus and the human immune system. In this Opinion article, Gubler and colleagues discuss the gaps in our understanding of the molecular pathogenesis of dengue virus and call for a reassessment of the animal models used in the preclinical stages of dengue research.

Organophosphonates contain the chemically stable C–P bond and are the most abundant form of P in the biosphere. McGrath and colleagues review recent advances in our understanding of microbial phosphonate metabolism and the role of these compounds in the global P cycle.

Small ubiquitin-like modifier (SUMO) modifications have emerged as key regulators of many intracellular pathways. Here, Everett and colleagues review the interplay between viruses and the SUMO pathway in infected cells, and the consequences of these interactions for the viral life cycle and for intrinsic and innate immunity.

Microorganisms can form complex, spatially organized communities that are coordinated by both physical and chemical intercellular interactions, as well as by other molecules present in the surrounding environment. Here, Whiteley and colleagues describe a number of microscale techniques for reproducing small bacterial communities in the laboratory. They also discuss the analytical tools available to monitor the impact of spatial organization on both bacterial behaviour and the generation of phenotypic heterogeneity.

Many bacterial species have evolved specialized secretion systems that deliver effector proteins into host cells in order to promote bacterial survival and replication. To exert their functions in a spatially coordinated manner, effector proteins must be accurately targeted to specific subcellular compartments. Here, Hicks and Galán review how bacterial effectors exploit the host cell machinery involved in processes such as lipidation and ubiquitylation to accurately target the biochemical activities of these effectors within the host cell.

In vitrosingle-molecule technologies have emerged as powerful tools for the study of complex biological phenomena. Here, Robinson and van Oijen summarize the latest insights that fluorescence-based single-molecule studies have provided for DNA replication, transcription and translation in bacterial cells.

The bacterial nucleoid was first described more than 50 years ago, but the recent application of new imaging technologies and physical analytical methods has brought fresh insights to the structure of the DNA within the nucleoid. Here, Charles Dorman discusses these insights and argues that, in addition to DNA topology and nucleoid-associated proteins, gene regulation is an important organizing principle of nucleoid architecture.

RNA viruses have extremely high mutation rates, which are crucial for the ability of these viruses to adapt but can also lead to population extinction. Here, Andino and colleagues describe the mechanisms that RNA viruses use to cope with the high mutational load and discuss the impact of mutational robustness on population dynamics, pathogenicity and antiviral therapies.

Many plants engage in symbiotic associations with microorganisms, in which the interactions are beneficial to both partners. Two of the best studied partnerships are rhizobial and mycorrhizal colonization. Giles Oldroyd highlights the commonalities in the symbiosis signalling pathways involved in these associations and how, despite these commonalities, sufficient specificity is maintained to ensure appropriate responses to each symbiont.

The ability of human papillomaviruses (HPVs) to cause disease is strongly dependent on the strict coordination of viral gene expression with the differentiation state of the infected cell. Here, Johansson and Schwartz summarize the role of splicing and polyadenylation in the regulation of HPV gene expression and discuss the viral and cellular factors that control these processes.

In recent years, nine new human polyomaviruses have been discovered, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. DeCaprio and Garcea compare and contrast these new human viruses and discuss how they might interact with their human host.

Perturbations in the gut microbiota can lead to a state of dysbiosis, which may involve 'blooming' of potentially harmful bacteria. Here, Hardt and colleagues propose that such bacteria blooms promote horizontal gene transfer between members of the gut ecosystem, thereby facilitating pathogen evolution.

In this Opinon article, Cornforth and Foster argue that several of the major bacterial stress responses detect ecological competition directly through competition sensing, a physiological response that detects harm caused by other cells and that evolved, at least in part, for that purpose. In support of this argument, they show that bacteriocins and antibiotics are frequently upregulated by stress responses to nutrient limitation and cell damage but not by responses to abiotic stress.

The gut microbiota, traditionally studied in the context of disease, has emerged as a key regulator during normal homeostasis. Here, Sommer and Bäckhed discuss how the gut microbiota promotes the development and homeostasis of the immune system and orchestrates several aspects of human physiology, including tissue morphogenesis, metabolism and even behaviour.

Small RNAs (sRNAs) are used by plants, nematodes and arthropods in cellular defence against viruses, but in chordates, sRNAs were replaced with a protein-based system to inhibit viral replication. Here, Benjamin tenOever describes how the lack of interplay between cellular sRNAs and RNA viruses permits the engineering of vectors that can deliver their own sRNAs or are controlled by the sRNAs present in the host.

In addition to developing vaccines and drugs that target vector-borne diseases, historically the use of insecticides has been the main approach for targeting the vector itself. However, as McGraw and O'Neill describe in this Review, there has been substantial recent progress in developing alternative genetic and biological vector-control strategies.