Establishing mutualistic relationships between plants and fungi is crucial for overcoming nutrient deficiencies in plants. This review highlights the intricate nutrient sensing and uptake mechanisms used by plants in response to phosphate and nitrogen starvation, as well as their interactions with plant immunity. The coordination of transport systems in both host plants and fungal partners ensures efficient nutrient uptake and assimilation, contributing to the long-term maintenance of these mutualistic associations. It is also essential to understand the distinct responses of fungal partners to external nutrient levels and forms, as they significantly impact the outcomes of symbiotic interactions. Our review also highlights the importance of evolutionarily younger and newly discovered root-fungus associations, such as endophytic associations, which offer potential benefits for improving plant nutrition. Mechanistic insights into the complex dynamics of phosphorus and nitrogen sensing within diverse root-fungus associations can facilitate the identification of molecular targets for engineering symbiotic systems and developing plant phenotypes with enhanced nutrient use efficiency. Ultimately, this knowledge can inform tailored fertilizer management practices to optimize plant nutrition.

Life can be stressful. One way to deal with stress is to simply wait it out. Microbes do this by entering a state of reduced activity and increased resistance commonly called 'dormancy'. But what is dormancy? Different scientific disciplines emphasize distinct traits and phenotypic ranges in defining dormancy for their microbial species and system-specific questions of interest. Here, we propose a unified definition of microbial dormancy, using a broad framework to place earlier discipline-specific definitions in a new context. We then discuss how this new definition and framework may improve our ability to investigate dormancy using multi-omics tools. Finally, we leverage our framework to discuss the diversity of genomic mechanisms for dormancy in an extreme environment that challenges easy definitions - the permafrost.

Antibiotics often contain ester bonds. The macrocyclic lactones of macrolides are pre-eminent examples in which ester bonds are essential to the form and function of antibiotics. Bacterial macrolide esterases that hydrolyze these macrocyclic lactones to confer antimicrobial resistance (AMR) are the topic of this forum. We provide insight into their role in agricultural systems and discuss their emergence and their potential extensibility to bioremediation efforts.

The aetiologic agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), can survive, persist, and proliferate in a variety of heterogeneous subcellular compartments. Therefore, TB chemotherapy requires antibiotics crossing multiple biological membranes to reach distinct subcellular compartments and target these bacterial populations. These compartments are also dynamic, and our understanding of intracellular pharmacokinetics (PK) often represents a challenge for antitubercular drug development. In recent years, the development of high-resolution imaging approaches in the context of host-pathogen interactions has revealed the intracellular distribution of antibiotics at a new level, yielding discoveries with important clinical implications. In this review, we describe the current knowledge regarding cellular PK of antibiotics and the complexity of drug distribution within the context of TB. We also discuss the recent advances in quantitative imaging and highlight their applications for drug development in the context of how intracellular environments and microbial localisation affect TB treatment efficacy.

Symbioses involving microorganisms prevail in nature and are key to regulating numerous ecosystem processes and in driving evolution. A major concern in understanding the ecology of symbioses involving microorganisms arises in the effectiveness of sampling strategies to capture the contrasting size of organisms involved. In many mutualisms, including mycorrhizas and gut systems, hosts interact simultaneously with multiple smaller sized mutualists, the identity of which determines success for the host. This complicates quantifying the diversity of mutualisms because sampling techniques fail to capture effectively the diversity of each partner. Here we propose the use of species-area relationships (SARs) to explicitly consider the spatial scale of microbial partners in symbioses, which we propose will improve our understanding of the ecology of mutualisms.

Studies of the gut microbiota have revealed associations between specific bacterial species or community compositions with health and disease, yet the causal mechanisms underlying microbiota gene-host interactions remain poorly understood. This is partly due to limited genetic manipulation (GM) tools for gut bacteria. Here, we review current advances and challenges in the development of GM approaches, including clustered regularly interspaced short palindromic repeats (CRISPR)-Cas and transposase-based systems in either model or non-model gut bacteria. By overcoming barriers to 'taming' the gut microbiome, GM tools allow molecular understanding of host-microbiome associations and accelerate microbiome engineering for clinical treatment of cancer and metabolic disorders. Finally, we provide perspectives on the future development of GM for gut microbiome species, where more effort should be placed on assembling a generalized GM pipeline to accelerate the application of groundbreaking GM tools in non-model gut bacteria towards both basic understanding and clinical translation.

Orthohantaviruses present a global public health threat; there are 58 distinct viruses currently recognized and case fatality of pathogenic orthohantaviruses ranges from <0.1% to 50%. An Old World versus New World dichotomy is frequently applied to distinguish human diseases caused by orthohantaviruses. However, this geographic grouping masks the importance of phylogeny and virus-host ecology in shaping orthohantavirus traits, especially since related arvicoline rodents and their orthohantaviruses are found in both regions. We argue that orthohantaviruses can be separated into three phylogenetically based rodent host groups with differences in key functional traits, including human disease, transmission route, and virus-host fidelity. This framework can help understand and predict traits of under-studied and newly discovered orthohantaviruses and guide public health and biosafety policy.

Bacterial photosynthesis is essential for sustaining life on Earth as it aids in carbon assimilation, atmospheric composition, and ecosystem maintenance. Many bacteria utilize anoxygenic photosynthesis to convert sunlight into chemical energy while producing organic matter. The core machinery of anoxygenic photosynthesis performed by purple photosynthetic bacteria and Chloroflexales is the reaction center-light-harvesting 1 (RC-LH1) pigment-protein supercomplex. In this review, we discuss recent structural studies of RC-LH1 core complexes based on the advancement in structural biology techniques. These studies have provided fundamental insights into the assembly mechanisms, structural variations, and modularity of RC-LH1 complexes across different bacterial species, highlighting their functional adaptability. Understanding the natural architectures of RC-LH1 complexes will facilitate the design and engineering of artificial photosynthetic systems, which can enhance photosynthetic efficiency and potentially find applications in sustainable energy production and carbon capture.

Viroids are single-stranded circular noncoding RNAs that infect plants. According to the International Committee on Taxonomy of Viruses, there are 44 viroids known to date. Notably, more than 20 000 distinct viroid-like RNA sequences have recently been identified in existing sequencing datasets, suggesting an unprecedented complexity in biological roles of viroids and viroid-like RNAs. Interestingly, a human pathogen, hepatitis delta virus (HDV), also replicates via a rolling circle mechanism like viroids. Therefore, knowledge of viroid infection is informative for research on HDV and other viroid-like RNAs reported from various organisms. Here, we summarize recent advancements in understanding viroid shuttling among subcellular compartments for completing replication cycles, emphasizing regulatory roles of RNA motifs and structural dynamics in diverse biological processes. We also compare the knowledge of viroid intracellular trafficking with known pathways governing cellular RNA movement in cells. Future investigations on regulatory RNA structures and cognate factors in regulating viroid subcellular trafficking and replication will likely provide new insights into RNA structure-function relationships and facilitate the development of strategies controlling RNA localization and function in cells.

Gram-negative bacteria deliver effector proteins through type III, IV, or VI secretion systems (T3SSs, T4SSs, and T6SSs) into host cells, causing infections and diseases. In general, effector proteins for each of these distinct secretion systems lack homology and are difficult to identify. Sequence analysis has disclosed many common features, helping us to understand the evolution, function, and secretion mechanisms of the effectors. In combination with various algorithms, the known common features have facilitated accurate prediction of new effectors. Ensemblers or integrated pipelines achieve a better prediction of performance, which combines multiple computational models or modules with multidimensional features. Natural language processing (NLP) models also show the merits, which could enable discovery of novel features and, in turn, facilitate more precise effector prediction, extending our knowledge about each secretion mechanism.

Cyanobacteria generate energy from photosynthesis and produce various secondary metabolites with diverse commercial and pharmaceutical applications. Unique metabolic and regulatory pathways in cyanobacteria present new challenges for researchers to enhance their product yields, titers, and rates. Therefore, further advancements are critically needed to establish cyanobacteria as a preferred bioproduction platform. Metabolic flux analysis (MFA) quantitatively determines the intracellular flows of carbon within complex biochemical networks, which elucidate the control of metabolic pathways by transcriptional, translational, and allosteric regulatory mechanisms. The emerging field of systems metabolic engineering (SME) involves the use of MFA and other omics technologies to guide the rational development of microbial production strains. This review highlights the potential of MFA and SME to optimize the production of cyanobacterial secondary metabolites and discusses the technical challenges that lie ahead.

A growing body of research, especially in recent years, has shown that bacterial extracellular vesicles (bEVs) are one of the key underlying mechanisms behind the pathogenesis of various diseases like pulmonary fibrosis, sepsis, systemic bone loss, and Alzheimer's disease. Given these new insights, bEVs are proposed as an emerging vehicle that can be used as a diagnostic tool or to tackle diseases when used as a therapeutic target. To further boost the understanding of bEVs in health and disease we thoroughly discuss the contribution of bEVs in disease pathogenesis and the underlying mechanisms. In addition, we speculate on their potential as novel diagnostic biomarkers and how bEV-related mechanisms can be exploited as therapeutic targets.

SARS-CoV-2, the causative agent of COVID-19, primarily affects the epithelial compartment in the upper and lower airways. There is evidence that the microvasculature in both the pulmonary and extrapulmonary systems is a major target of SARS-CoV-2. Consistent with this, vascular dysfunction and thrombosis are the most severe complications in COVID-19. The proinflammatory milieu triggered by the hyperactivation of the immune system by SARS-CoV-2 has been suggested to be the main trigger for endothelial dysfunction during COVID-19. More recently, a rapidly growing number of reports have indicated that SARS-CoV-2 can interact directly with endothelial cells through the spike protein, leading to multiple instances of endothelial dysfunction. Here, we describe all the available findings showing the direct effect of the SARS-CoV-2 spike protein on endothelial cells and offer mechanistic insights into the molecular basis of vascular dysfunction in severe COVID-19.

Calcium signaling is an essential mediator of signal-controlling gene expression in most developmental systems. In addition, calcium has established extracellular functions as a structural component of biogenic minerals found in complex tissues. In bacteria, the formation of calcium carbonate structures is associated with complex colony morphology. Genes promoting the formation of biogenic minerals are essential for proper biofilm development and protection against antimicrobial solutes and toxins. Here we review recent findings on the role of calcium and calcium signaling as emerging regulators of biofilm formation in beneficial bacteria, as well as essential mediators of biofilm formation and virulence in human pathogens. The presented analysis concludes that the new understanding of calcium signaling may help to improve the performance of beneficial strains for sustainable agriculture, microbiome manipulation, and sustainable construction. Unraveling the roles of calcium may also promote the development of novel therapies against biofilm infections that target calcium uptake, calcium sensors, and calcium carbonate deposition.

The recent revolution in imaging techniques and results from RNA footprinting in situ reveal how the bacteriophage MS2 genome regulates both particle assembly and genome release. We have proposed a model in which multiple packaging signal (PS) RNA-coat protein (CP) contacts orchestrate different stages of a viral life cycle. Programmed formation and release of specific PS contacts with CP regulates viral particle assembly and genome uncoating during cell entry. We hypothesize that molecular frustration, a concept introduced to understand protein folding, can be used to better rationalize how PSs function in both particle assembly and genome release. More broadly this concept may explain the directionality of viral life cycles, for example, the roles of host cofactors in HIV infection. We propose that this is a universal principle in virology that explains mechanisms of host-virus interaction and suggests diverse therapeutic interventions.

Acinetobacter baumannii is a Gram-negative opportunistic bacterium responsible for nosocomial and community-acquired infections. This pathogen is globally disseminated and associated with high levels of antibiotic resistance, which makes it an important threat to human health. Recently, new evidence showed that several A. baumannii isolates can survive and proliferate within eukaryotic professional and/or nonprofessional phagocytic cells, with in vivo consequences. This review provides updated information and describes the tools that A. baumannii possesses to adhere, colonize, and replicate in host cells. Additionally, we emphasize the high genetic and phenotypic heterogeneity detected amongst A. baumannii isolates and its impact on the bacterial intracellular features. We also discuss the need for standardized methods to characterize this pathogen robustly and consequently consider some strains as facultative intracellular bacteria.

Reactive oxygen species (ROS), including the superoxide radical anion (O2•-), hydrogen peroxide (H2O2), and the hydroxyl radical (•HO), are inherent components of bacterial metabolism in an aerobic environment. Bacteria also encounter exogenous ROS, such as those produced by the host cells during the respiratory burst. As ROS have the capacity to damage bacterial DNA, proteins, and lipids, detoxification of ROS is critical for bacterial survival. It has been recently recognised that low-molecular-weight (LMW) thiols play a central role in this process. Here, we review the emerging role of cysteine in bacterial resistance to ROS with a link to broader elements of bacterial lifestyle closely associated with cysteine-mediated oxidative stress response, including virulence and antibiotic resistance.

Plant reoviruses, transmitted only by insect vectors, seriously threaten global cereal production. Understanding how insect vectors efficiently transmit the viruses is key to controlling the viral diseases. Autophagy commonly plays important roles in plant host defense against virus infection, but recent studies have shown that plant reoviruses can hijack the autophagy pathway in insect cells to enable their persistence in the insect and continued transmission to plants. Here, we summarize and discuss new insights on viral activation, evasion, regulation, and manipulation of autophagy within the insect vectors and the role of autophagy in virus survival in insect vectors. Deeper knowledge of the functions of autophagy in vectors may lead to novel strategies for blocking transmission of insect-borne plant viruses.

Microbes are key biodiversity components of all ecosystems and control vital ecosystem functions. Although we have just begun to unravel the scales and factors that regulate microbial communities, their role in mediating ecosystem stability in response to disturbances remains underexplored. Here, we review evidence of how, when, and where microbes regulate or drive disturbance feedbacks. Negative feedbacks dampen the impacts of disturbance, which maintain ecosystem stability, whereas positive feedbacks instead erode stability by amplifying the disturbance. Here we describe the processes underlying the responses to disturbance using a hierarchy of functional traits, and we exemplify how these may drive biogeochemical feedbacks. We suggest that the feedback potential of functional traits at different hierarchical levels is contingent on the complexity and heterogeneity of the environment.

While the diversity of global environmental RNA viruses has remained largely unexplored, recent advances have reported on the discovery of over 106 RNA viral contigs from both terrestrial and marine ecosystems that will help us to better understand the diversity, evolution, ecological roles, and transmission of RNA viruses.