Reviews & Analysis

Accumulating evidence suggests that the gut microbiota has a role in the aetiology of colorectal cancer (CRC). In this Review, Flint and colleagues discuss the complex interplay between diet, the microbiota and microbial metabolites and argue that the combined metabolome of the microbiota has both protective and detrimental effects on inflammation and the progression of CRC.

The Hawaii Ocean Time-series programme recently completed 25 years of continuous operation. Matthew Church and David Karl look back on some of the major discoveries that have come from this long-term programme and its contribution to our evolving understanding of microbial oceanography.

Marine phytoplankton blooms are annual spring events that are accompanied by a surge in heterotrophic bacteria, primarily roseobacters, flavobacteria and members of the Gammaproteobacteria, which recycle most of the carbon that is fixed by the primary producers. In this Review, Buchanet al. describe the emerging physiological features and functions of these bacterial communities and their interactions with phytoplankton.

Pathogens block or subvert host cellular processes to promote successful infection. One host protein that is targeted by invading pathogens is the small GTPase RAB11, which functions in vesicular trafficking. Bier and colleagues discuss the various mechanisms that pathogens have evolved to disrupt or subvert RAB11-dependent pathways as part of their infection strategy.

Kirchhoff and colleagues discuss the discovery of novel antimicrobial peptides by systematic screening of complex peptide and protein libraries that have been derived from human bodily fluids and tissues, with a focus on the isolation of endogenous agents that affect HIV-1 infection.

The mouse pathogenCitrobacter rodentium has long been used as a model for investigating the pathogenesis of the important enteric human pathogens, enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli(EPEC). In this Review, Frankel and colleagues discuss the infection cycle of this pathogen, the mucosal immune response that is elicited and the role of the gut microbiota in preventing colonization.

It has recently emerged that pervasive transcription is widespread in bacteria and is caused by transcription from non-canonical promoters and terminator readthrough. However, whether the resultant transcripts have any functional role is unclear. In this Opinion article, Wade and Grainger argue that pervasive transcripts are likely to be important for the regulation of gene expression and genome evolution.

Although studies in 2D cell culture systems have provided great insights into the biology and pathogenesis of HIV-1 infection, such studies cannot account for many aspects of host physiology that affect HIV-1in vivo. Fackler et al. discuss the development and application of more integrative studies, including organotypic 3D culture systems, small-animal models and advanced live-cell imaging, and the impact of such studies on our understanding of the mechanisms of HIV-1 spread.

Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to a range of eukaryotic proteins to promote bacterial pathogenesis. In this Review, the authors discuss the structural and functional properties of the most recently identified novel bARTTs, which are produced by various human, insect and plant pathogens and were identified using bioinformatic analyses.

Compared with traditional model bacteria, the processes of growth and division are unusual in mycobacteria. In this Review, Rubin and Kieser discuss polar growth, asymmetric division and cell wall remodelling in mycobacteria and consider how these processes might contribute to the population heterogeneity and pathogenesis ofMycobacterium tuberculosis.

The development of a vaccine againstStaphylococcus aureusinfection has been the subject of an intensive research effort, but none of the vaccine trials has been successful so far. In this Opinion article, the authors suggest that an over-reliance on mouse models and a focus on targeting cell surface components have been major contributing factors to this failure.

Humans can resist infection by African trypanosomes, owing to the trypanolytic activity of apolipoprotein L1 (APOL1), which is associated with two serum complexes, trypanosome lytic factor 1 (TLF1) and TFL2.Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense evade this defence mechanism by expressing resistance proteins and in turn, populations in western Africa can restore resistance to T. b. rhodesiense via sequence variation in APOL1. Pays et. al. review this complex relationship and its evolutionary importance.

Botulinum neurotoxins, which are the most powerful known toxins, are produced by toxigenic clostridia and cause persistent paralysis of peripheral nerve terminals by blocking neurotransmitter release. In this Review, Montecucco and colleagues discuss recent structural and molecular insights into the mechanisms of toxin entry into nerve terminals, membrane translocation and neuroparalysis.

Long-range intragenomic RNA–RNA interactions in the genomes of positive-strand RNA viruses involve direct nucleotide base pairing and can span distances of thousands of nucleotides. In this Review, Nicholson and White discuss recent insights into the structure and function of these genomic features and highlight their diverse roles in the gene expression and genome replication of positive-strand RNA viruses.

The protozoan parasiteTrypanosoma bruceihas a single flagellum that is present in all of its different developmental stages. In this Review, Langousis and Hill discuss the structural and functional features of the flagellum and highlight its central role in the virulence and transmission of this important human pathogen.

In this Review, van der Oostet al. summarize the recent structural and biochemical insights into the molecular mechanisms of RNA-guided interference by CRISPR–Cas systems in bacteria and archaea. By comparing the three main types of CRISPR–Cas systems, they highlight the unique and conserved properties of the system and also discuss outstanding questions that require further study.

Bacteria are frequently exposed to subinhibitory concentrations of antibiotics, and recent evidence suggests that this is likely to select for resistance. In this Review, Andersson and Hughes discuss the ecology of antibiotics, the ability of subinhibitory concentrations of antibiotics to select for resistance and the effects of low-level drug exposure on bacterial physiology.

Platelets are multifunctional granulocytes that function at the intersection of antimicrobial and haemostatic host defences. Michael R. Yeaman presents an integrated overview of the antimicrobial functions of platelets, which are mediated both directly and indirectly to integrate innate and adaptive immune responses to pathogens.

McInerney and colleagues summarize the phylogenetic, cell biological, population biology, biochemical and paleontological evidence that cellular life consists of two primary, paraphyletic, prokaryotic groups and one secondary, monophyletic group that has symbiogenic origins — the eukaryotes.

One-quarter of the land surface on Earth is underlain by permafrost. Jansson and Taş review the microbial ecology of this fascinating and unique niche, pulling together observations from the study of permafrost isolates and the application of high-throughput sequencing.