Reviews & Analysis

Bacterial pathogens have evolved diverse strategies to interfere with and modulate the ubiquitin systems of the host for their own benefit. In this Review, Sasakawa and colleagues discuss the mechanisms that are involved, with a focus on secreted effector proteins that are delivered into the host cell by human bacterial pathogens.

Much of synthetic biology research makes use of model organisms, such asEscherichia coli. Here, Víctor de Lorenzo and colleagues emphasize the need for a wider choice of model organisms and advocate the use of environmental Pseudomonasstrains as model organisms that possess the necessary metabolic traits required to meet current and future synthetic biology and biotechnological needs.

Non-coding RNA devices, such as CRISPR–Cas systems, riboswitches and RNA scaffolds, have emerged as a versatile class of genetic regulatory elements that are used in a broad range of synthetic biology applications. In this Review, Arkin and Qi discuss the design, engineering and application of synthetic non-coding RNA devices for microbial engineering.

Although the CRISPR–Cas system of prokaryotes has an established role in defence, recent studies suggest that this system has other functional roles. Here, Westra and colleagues explore the more unconventional roles of CRISPR–Cas, such as endogenous gene regulation and genome remodelling, and consider their evolutionary implications.

In this Timeline article, Collins and colleagues chart the history of synthetic biology since its inception just over a decade ago, with a focus on both the cultural and scientific progress that has been made as well as on key breakthroughs and areas for future development.

Entry of the antimalarial drug precursor semi-synthetic artemisinin into industrial production is the first major milestone for the application of synthetic biology. In this Review, Paddon and Keasling discuss the metabolic engineering and synthetic biology approaches that were used to engineerEscherichia coli and Saccharomyces cerevisiaeto synthesize a precursor of artemisinin, which should aid the development of other pharmaceutical products.

In this Review, Sauer and colleagues outline how microorganisms coordinate common metabolic tasks. By illustrating the information transfer and flux adaptation for key regulatory circuits inEscherichia coli, Bacillus subtilisand yeast, they conclude that cells rely on a few conserved metabolites to report on their global metabolic status and mount appropriate responses.

Antivirulence drugs are a promising avenue to revitalize the antimicrobial drug-development pipeline, and it has been claimed that such compounds will generate much weaker selection for resistance than traditional antibiotics. Sam P. Brown and colleagues examine this claim and argue that, although resistance to antivirulence drugs may emerge, the crucial factor is whether or not this resistance will spread.

Although once thought to be clonal, and thus undergo asexual reproduction, accumulating evidence now suggests that many human fungal pathogens retain sexual reproductive machinery and undergo sexual or parasexual reproduction. Iuliana V. Ene and Richard J. Bennett discuss the sexual cycles of three of the most prominent human pathogens —Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus.

The causative agent of whooping cough,Bordetella pertussis, has recently re-emerged as a serious public health concern. Here, Cotter, Miller and colleagues discuss the pathogenesis of pertussis, the shortcomings of current vaccines and the future challenges that need to be addressed for the development of more effective therapeutic strategies.

Wild populations of bacteria and archaea show high levels of genotypic diversity. In this Review, Cordero and Polz discuss recent studies that show that this diversity arises owing to social and ecological interactions, which have important consequences for microbial ecology and population dynamics.

Protective immunity against tuberculosis is multifactorial, and correlates of protection — either during natural infection or after vaccination — are lacking. Here, Behar and colleagues discuss why it is time to look beyond interferon-γ for protective mechanisms againstMycobacterium tuberculosis.

Mortality from influenza viruses is strongly linked to secondary bacterial invaders. Here, Jonathan A. McCullers reviews viral and bacterial virulence factors that contribute to the pathogenesis of co-infections by disrupting physical barriers, dysregulating immune responses and delaying a return to homeostasis.

Paracrystalline arrays of proteins decorate the surface of many bacteria. In this Review, Fagan and Fairweather discuss recent insights into the structural and functional properties of these surface layers, which are beginning to reveal their importance for the growth and survival of many species.

Varicella zoster virus is so well adapted to its human host that studying its pathogenesis heavily relies on human tissue transplants in immunodeficient mice. Here, Arvin and colleagues describe insights from these models that show how this viral pathogen orchestrates host cell and tissue functions to its own advantage.

David M. Whiley and colleagues discuss the problem of antimicrobial resistance (AMR) inNeisseria gonorrhoeae, particularly emerging resistance to the cephalosporin ceftriaxone, and propose the use of molecular approaches to enhance gonococcal AMR surveillance.

In this Review, Claverys and colleagues describe the divergent and common principles that govern the transformation process in phylogenetically distinct bacteria and discuss the potential role of imported DNA in generating genetic diversity. They also discuss how this information can be used for the prediction of new transformable species.

Termites depend on an intricate symbiosis with flagellated protists, archaea and bacteria in their guts for the digestion of lignocellulose. Here, Andreas Brune gives an overview of the diversity of the termite microbiota and highlights important microbial processes in the gut microecosystem and their implications for host nutrition.

Understanding the pharmacokinetic and pharmacodynamic properties of anti-tuberculosis drugs is crucial for designing more effective dosing regimens. In this Progress article, Véronique Dartois describes the methods that are available to monitor the distribution of drugs as they travel from the blood compartment to granulomatous lesions and penetrate infected immune cells to finally reach their intended targets inside mycobacterial cells.

In this Review, van Wezel and colleagues discuss recent studies that have improved our understanding of the processes that lead to bacterial multicellularity. By considering phylogenetically diverse bacteria, the authors explore the evolutionary and ecological consequences of multicellular behaviour.