Novel whole-cell bacterial biosensor designs require an emphasis on moving toward field deployment. Many current sensors are characterized under specified laboratory conditions, which frequently do not represent actual deployment conditions. To this end, recent developments such as toolkits for probing new host chassis that are more robust to environments of interest, have paved the way for improved designs. Strategies for rational tuning of genetic components or tools such as genetic amplifiers or designs that allow post hoc tuning are essential in optimizing existing biosensors for practical application. Furthermore, recent work has seen a rise in directed evolution techniques, which can be immensely valuable in both tuning existing sensors and developing sensors for new analytes that lack characterized sensors. Combined with advancements in bioinformatics and capabilities in rewiring two-component systems, many new sensors can be established, broadening biosensor use cases. Last, recent work in CRISPR-based dynamic regulation and memory mechanisms, as well as kill-switches for biosafety and innovative output integration concepts, represents promising steps toward designing bacterial biosensors for deployment in dynamic and heterogeneous conditions.

Mammalian microbiomes have coevolved with their host to establish a stable homeostatic relationship. Multifaceted commensal-host and commensal-commensal interactions contribute to the maintenance of the equilibrium with an impact on diverse host physiological processes. Despite constant exposure to physical and chemical insults from the environment, the skin harbors a surprisingly stable microbiome. The fungal compartment of the skin microbiome, the skin mycobiome, is unique in that it is dominated by a single fungus, Malassezia. The lack in diversity suggests that the skin may provide a unique niche for this fungal genus and that Malassezia may efficiently outcompete other fungi from the skin. This opinion article examines aspects in support of this hypothesis, discusses how changes in niche conditions associate with skin mycobiome dysregulation, and highlights an emerging example of Malassezia being displaced from the skin by the emerging fungal pathogen C. auris, thereby generating a predisposing situation for fatal-invasive infection.

To fight antimicrobial resistance (AMR), we must recognize and target all its manifestations. In this review, we briefly summarize the history that led to recognition of the various manifestations of AMR in bacterial pathogens and the ways in which they interrelate. We emphasize the importance of distinguishing between AMR arising from genetic alterations versus induction of endogenous machinery in response to environmental triggers, including - paradoxically - stresses from host immunity and antimicrobial therapy. We present an integrated view of AMR by reframing it as a spectrum of phenotypes within a continuous three-dimensional space defined by the growth rate, prevalence, and kill rate of cells displaying AMR. Finally, we reflect on strategies that may help stem the emergence of AMR.

Multiple eukaryotic cell processes are modulated by calcium ions (Ca2+). As such, Ca2+ is emerging as a crucial regulator of innate immunity in multicellular organisms. In particular, recent studies have identified roles of Ca2+ signalling at the host-bacteria interface. Following microbial exposure, Ca2+ signals mobilised from the extracellular milieu or intracellular stores are transduced into cell physiological responses. However, during infection with host-adapted pathogens, Ca2+ signals are often atypical, due to the activities of virulence factors, with varied consequences for both the pathogen and the host cell. In this review, we describe the Ca2+-dependent host factors regulating antibacterial immunity, in addition to bacterial effectors that promote, inhibit, or co-opt Ca2+-calmodulin signalling to promote infection.

Plants recruit a taxonomically diverse microbial community, collectively termed the plant microbiome, that includes mutualists, pathogens, and commensals. These myriad microorganisms are robustly intertwined with their hosts and can determine plant fate by influencing fitness and growth or offering protection from detrimental bacteria, fungi, and herbivores. Recent studies have revealed significant effects of host genome diversity on plant-microbiome assembly and how host genetics determine microbiome composition, which is crucial for beneficial functions. The few host loci identified through genome-wide association studies suggest that genes involved in plant development, immunity, nutrient uptake, and root exudates regulate plant-microbiome community structure. Elucidating the role of host genetics in plant-microbiome assembly is key to understanding how plant-microbiome interactions are evolving and how to unlock the breeding and engineering potential of the microbiome for sustainable agriculture.

Harnessing the power of beneficial microbes in the rhizosphere to improve crop performance is a key goal of sustainable agriculture. However, the precise management of rhizosphere microbes for crop growth and health remains challenging because we lack a comprehensive understanding of the plant-rhizomicrobiome relationship. In this review, we discuss the latest research progress on root colonisation by representative beneficial microbes (e.g. Bacillus spp. and Pseudomonas spp.). We also highlight the bidirectional chemical communication between microbes and plant roots for precise functional control of beneficial microbes in the rhizosphere, as well as advances in understanding how beneficial microbes overcome the immune system of plants. Finally, we propose future research objectives that will help us better understand the complex network of plant-microbe interactions.

Earth's climate crisis threatens to disrupt ecosystem services and destabilize food security. Microbiome management will be a crucial component of a comprehensive strategy to maintain stable microbinal functions for ecosystems and plants in the face of climate change. Microbiome rescue is the directed, community-level recovery of microbial populations and functions lost after an environmental disturbance. Microbiome rescue aims to propel a resilience trajectory for community functions. Rescue can be achieved via demographic, functional, adaptive, or evolutionary recovery of disturbance-sensitive populations. Various ecological mechanisms support rescue, including dispersal, reactivation from dormancy, functional redundancy, plasticity, and diversification, and these mechanisms can interact. Notably, controlling microbial reactivation from dormancy is a potentially fruitful but underexplored target for rescue.

Salmonella enterica is one of the most widespread bacterial pathogens found worldwide, resulting in approximately 100 million infections and over 200 000 deaths per year. Salmonella isolates, termed 'serovars', can largely be classified as either nontyphoidal or typhoidal Salmonella, which differ in regard to disease manifestation and host tropism. Nontyphoidal Salmonella causes gastroenteritis in many hosts, while typhoidal Salmonella is human-restricted and causes typhoid fever, a systemic disease with a mortality rate of up to 30% without treatment. There has been considerable interest in understanding how different Salmonella serovars cause different diseases, but the molecular details that underlie these infections have not yet been fully characterized, especially in the case of typhoidal Salmonella. In this review, we highlight the current state of research into understanding the pathogenesis of both nontyphoidal and typhoidal Salmonella, with a specific interest in serovar-specific traits that allow human-adapted strains of Salmonella to cause enteric fever. Overall, a more detailed molecular understanding of how different Salmonella isolates infect humans will provide critical insights into how we can eradicate these dangerous enteric pathogens.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, and one of the main pathogens responsible for otitis media infections in children. Amoxicillin (AMX) is a broad-spectrum β-lactam antibiotic, used frequently for the treatment of bacterial respiratory tract infections. Here, we discuss the pneumococcal response to AMX, including the mode of action of AMX, the effects on autolysin regulation, and the evolution of resistance through natural transformation. We discuss current knowledge gaps in the synthesis and translocation of peptidoglycan and teichoic acids, major constituents of the pneumococcal cell wall and critical to AMX activity. Furthermore, an outlook of AMX resistance research is presented, including the development of natural competence inhibitors to block evolution via horizontal gene transfer, and the use of high-throughput essentiality screens for the discovery of novel cotherapeutics.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), accounts for over ten million infections and over 1.5 million deaths every year [1]. Upon infection, the seesaw between Mtb and our immune systems creates microenvironments that are compositionally distinctive and changing over time. While the field has begun to better understand the spatial complexity of TB disease, our understanding and experimental dissection of the temporal dynamics of TB and TB drug treatment is much more rudimentary. However, it is the combined spatiotemporal heterogeneity of TB disease that creates niches and time windows within which the pathogen can survive and thrive during treatment. Here, we review the emerging data on the interactions of spatial and temporal dynamics as they relate to TB disease and treatment. A better understanding of the interactions of Mtb, host, and antibiotics through space and time will elucidate treatment failure and potentially identify opportunities for new TB treatment regimens.

The diversity of microbial ecosystems is linked to crucial ecological processes and functions. Despite its significance, the ecological mechanisms responsible for the initiation and maintenance of microbiome diversity are still not fully understood. The primary challenge lies in the difficulty of isolating, monitoring, and manipulating the complex and interrelated ecological processes that modulate the diversity of microbial communities in their natural habitats. Synthetic ecology experiments provide a suitable alternative for investigating the mechanisms behind microbial biodiversity in controlled laboratory settings, as the environment can be systematically and modularly manipulated by adding and removing components. This enables the testing of hypotheses and the advancement of predictive theories. In this review, we present an overview of recent progress toward achieving this goal.

COVID-19 pandemic highlighted the complications of secondary fungal infections that occurred globally in severe cases of coronavirus disease managed in the intensive care units. Furthermore, varied underlying host factors, such as preexisting immunosuppression, the use of immunomodulatory agents, and invasive procedures predisposing lung tissues to fungal colonization and proliferation, caused increased susceptibility to fungal infections in COVID-19 patient populations. These invasive fungal infections directly impact the overall length of hospitalization and mortality. The most commonly reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis. An overall worldwide increase in the prevalence of candidiasis and aspergillosis was observed in COVID-19 patients , whereas outbreaks of mucormycosis were mainly recorded from India. Diagnostic challenges and limited antifungal treatment options make secondary fungal infections among COVID-19 patients more burdensome, which results in improper management and increased mortality.

Most of the variance in the human microbiome remains unexplained. Although an extensive list of individual lifestyles shaping the microbiome has been identified, important gaps in knowledge persist. Most human microbiome data are from individuals living in socioeconomically developed countries. This may have skewed the interpretation of microbiome variance and its relationship to health and disease. Moreover, striking under-representation of minority groups in microbiome studies is a missed opportunity to assess context, history and the changing nature of the microbiome in relation to the risk of disease. Therefore, we focus here on areas of recent progress - ageing and ethnicity - both of which contribute to microbiome variance with particular lessons for the promise of microbiome-based diagnostics and therapeutics.

Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic resistance, in particular, is not just a property of individual bacteria or even single-strain populations, but depends heavily on the community context. Collective community dynamics can lead to counterintuitive eco-evolutionary effects like survival of less resistant bacterial populations, slowing of resistance evolution, or population collapse, yet these surprising behaviors are often captured by simple mathematical models. In this review, we highlight recent progress - in many cases, advances driven by elegant combinations of quantitative experiments and theoretical models - in understanding how interactions between bacteria and with the environment affect antibiotic resistance, from single-species populations to multispecies communities embedded in an ecosystem.

Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials investigating antibiotics fail. So far, bacterial survival strategies, other than drug resistance, have been largely ignored. As such, drug tolerance and persisters, allowing bacterial populations to survive during antibiotic treatments, could fill a gap in antibiotic susceptibility testing. Therefore, it remains critical to establish robust and scalable bacterial viability measures and to define the clinical relevance of bacterial survivors across various bacterial infections. If successful, these tools could improve drug design and development to prevent tolerance formation or target bacterial survivors, to ultimately reduce treatment failures and curb resistance evolution.

Multicellular behavior benefits seemingly simple organisms such as bacteria, by improving nutrient uptake, resistance to stresses, or by providing advantages in predatory interactions. Several recent studies have shown that this also extends to the defense against bacteriophages, which are omnipresent in almost all habitats. In this review, we summarize strategies conferring protection against phage infection at the multicellular level, covering secretion of small antiphage molecules or membrane vesicles, the role of quorum sensing in phage defense, the development of transient phage resistance, and the impact of biofilm components and architecture. Recent studies focusing on these topics push the boundaries of our understanding of the bacterial immune system and set the ground for an appreciation of bacterial multicellular behavior in antiviral defense.

The formation of lateral microdomains is emerging as a central organizing principle in bacterial membranes. These microdomains are targets of antibiotic development and have the potential to enhance natural product synthesis, but the rules governing their assembly are unclear. Previous studies have suggested that microdomain formation is promoted by lipid phase separation, particularly by cardiolipin (CL) and isoprenoid lipids, and there is strong evidence that CL biosynthesis is required for recruitment of membrane proteins to cell poles and division sites. New work demonstrates that additional bacterial lipids may mediate membrane protein localization and function, opening the field for mechanistic evaluation of lipid-driven membrane organization in vivo.

Arbuscular mycorrhizal fungi (AMF) have accompanied the majority of land plants since their evolution in the Devonian period with a symbiotic alliance centered on nutrient exchanges. The exploration of AMF genomes is providing clues to explain major questions about their biology, evolution, and ecology. The dynamics of nuclei across the fungal life cycle, the abundance of transposable elements, and the epigenome landscape are emerging as sources of intraspecific variability, which can be especially important in organisms with no or rare sexual reproduction such as AMF. These features have been hypothesized to support AMF adaptability to a wide host range and to environmental changes. New insights on plant-fungus communication and on the iconic function of phosphate transport were also recently obtained that overall contribute to a better understanding of this ancient and fascinating symbiosis.

The innate immune system is the first line of defense against microbial pathogens. Many of the features of eukaryotic innate immunity have long been viewed as lineage-specific innovations, evolved to deal with the challenges and peculiarities of multicellular life. However, it has become increasingly apparent that in addition to evolving their own unique antiviral immune strategies, all lifeforms have some shared defense strategies in common. Indeed, critical fixtures of animal innate immunity bear striking resemblance in both structure and function to the multitude of diverse bacteriophage (phage) defense pathways discovered hidden in plain sight within the genomes of bacteria and archaea. This review will highlight many surprising examples of the recently revealed connections between prokaryotic and eukaryotic antiviral immune systems.

Antibiotic-resistant microbe-mediated deaths are a major worldwide health issue. Unfortunately, due to microbial adaptation to develop resistance, some antibiotics are nullified early in their usage, and worse, resistance is detected before they can even be prescribed. Copper's toxicity since antiquity against microbes at the host-pathogen interface offers a fascinating weapon to fight antimicrobial resistance. Here, we briefly review why copper is so effective, how drugs that work with copper are effective antimicrobials, and how compounds such as these could reinvigorate investment in antimicrobial development.