Reviews & Analysis

In this Review, Bjarnsholt and colleagues propose a revised conceptual model of the biofilm life cycle that encompasses the three major steps of biofilm formation — aggregation, growth and disaggregation — independently of surfaces, and initiation from single-cell planktonic bacteria, and thus represents a broader range of biofilm systems.

The human microbiota can undergo dramatic changes during different phases of life (for example, during colonization after birth, after disturbances or in old age). In this Review, Knight and colleagues discuss the microbiota successions that occur from the cradle to the grave.

The discovery of giant viruses, with virions as large as some bacteria and eukaryotes, megabase-range genomes, and a variety of traits typically found only in cellular organisms, was one of the most remarkable breakthroughs in biology. In this Review, Schulz, Abergel and Woyke explore insights into the biology, diversity, biogeography and ecology of giant viruses provided by culture and genomic technologies.

In this Review, Chandra, Grigsby and Philips discuss how Mycobacterium tuberculosis evades immune-mediated clearance while capitalizing on the host inflammatory response at different phases of its life cycle. They focus on recent studies, highlight gaps in knowledge and consider how our current understanding will inform new therapies, vaccines and diagnostics.

Bacteriophages are obligate parasites of their bacterial hosts; nevertheless, on a population level, phage–bacterium interactions can have beneficial outcomes. In this Review, Shkoporov, Turkington and Hill discuss the evidence for such mutualistic interactions in the gut microbiota and their roles.

Trace metals are essential micronutrients required for survival across all kingdoms of life. In this Review, Murdoch and Skaar discuss the strategies whereby vertebrate hosts limit metal or induce excess metal to prevent bacterial proliferation, a process termed nutritional immunity, and they discuss adaptive mechanisms that bacterial pathogens have evolved to survive in conditions of metal depletion or excess.

Marine biofilms grow on diverse marine surfaces, ranging from particles to animals and ships. In this Review, Qian and colleagues discuss the diversity and composition of marine biofilms and their role in the development of marine benthos and biofouling.

CRISPR–Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, Wang, Pausch and Doudna examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR–Cas immune systems and deployed for wide-ranging genome editing applications.

The anti-tuberculosis drug candidate pipeline is promising, but the recent breakthroughs are challenged with the need to prioritize drug combinations for clinical trials and revamping trial designs to accelerate regimen development. In this Review, Dartois and Rubin explore treatment challenges, drug development priorities, and approaches — from basic research to preclinical evaluation — that lead to the selection of drug combinations earlier in the discovery cascade to accelerate the approval of shorter treatment regimens.

In this Review, Greening and Grinter describe the microorganisms and enzymes that use atmospheric trace gases, including hydrogen, carbon monoxide and methane, during growth and survival. They highlight important ecological and biogeochemical roles for these processes in diverse environments, including ecosystem resilience under changing conditions.

In this Review, Aldridge and colleagues describe different types of mycobacterial heterogeneity and discuss how cell-to-cell heterogeneity and environmental heterogeneity are generated and regulated in response to environmental cues.

In this Review, Lamers and Haagmans explore recent clinical and experimental advances in understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis, interactions with host cells and the involvement of the immune system in the development of severe disease. Specifically, they focus on mechanisms underlying the development of COVID-19-associated acute respiratory distress syndrome.

The impacts of fungal infections on human health are of increasing concern, and resistance of pathogenic fungi to all licensed systemic antifungals has been documented. In this Review, Fisher, Verweij and colleagues discuss the research and innovation topics that are needed to understand and minimize the occurrence and impact of antifungal resistance.

The human gut microbiota produces an extensive array of carbohydrate-active enzymes to degrade carbohydrates derived from the diet, host and other microorganisms. Withers and colleagues discuss the vast diversity and activities of these enzymes and their potential applications.

In this Review, Wang and colleagues review the strategies microbial pathogens use to evade plant immunity for successful infection. They highlight how microbial effectors manipulate host cellular processes involved in immune sensing, signal integration and defence execution and how to exploit this knowledge to engineer crop resistance.

Chemotaxis is one of the best studied bacterial behaviours, but the underlying mechanisms are much better understood than the reasons and consequences of chemotaxis. In this Review, Keegstra et al. discuss the costs and benefits both for individual bacteria and whole populations.

Combining several antibiotics, either in mixtures or sequential order, is proposed to increase treatment efficacy and reduce resistance evolution. In this Review, Andersson and colleagues discuss the effects of antibiotic combinations, the directional effects of previous antibiotic treatments and the role of stress-response systems as well as the interactions between drugs and resistance mutations.

Soil microorganisms shape global element cycles in life and death. In this Review, Sokol and colleagues explore how the biogeochemical cycling of organic matter depends on both living and dead soil microorganisms, their functional traits, and their interactions with the soil matrix and other organisms. They also discuss incorporating microbial life and death into trait-based models that predict soil biogeochemical dynamics.

To maintain genome integrity and ensure cell survival, bacteria have evolved several DNA repair pathways to repair different types of DNA damage and non-canonical bases, including strand breaks, nucleotide modifications, cross-links, mismatches and ribonucleotide incorporations. In this Review, Wozniak and Simmons provide a contemporary discussion of the excision-based mechanisms bacteria use to repair the diverse set of lesions they encounter.

Osteomyelitis is an infection of bone that arises when a pathogen colonizes bone tissue owing to injury or surgery. In this Review, Masters and colleagues explore the microbial pathogenesis, immunity and clinical management of bone infections.