Cyanophages: Billions of Years of Coevolution with Cyanobacteria
Prevalent in marine and freshwater ecosystems, cyanophages compose a class of double-stranded DNA viruses that specifically infect cyanobacteria. During billions of years of coevolution, cyanophages and cyanobacteria have significantly contributed to the biogeochemical cycling and genetic diversity of aquatic ecosystems. As natural predators of cyanobacteria, cyanophages hold promise as eco-friendly agents against harmful cyanobacterial blooms. Recent technical advances in omics and cryo-electron microscopy have revealed the remarkable diversity of cyanophages in genome sequence and tail morphology. In this review, we summarize the genomic and metagenomic data, phylogenetic analyses, and diverse three-dimensional structures of cyanophages, in addition to their interplays with hosts. We also discuss the in vivo assembly processes of cyanophages, the exploration of uncultured cyanophages and host pairing, and the synthetic engineering and potential applications of cyanophages.
The Central Role of Gut Microbes in Host Purine Homeostasis
Purines are ubiquitous metabolites that play evolutionarily conserved roles, including as precursors to molecules central to life. Purine synthesis is metabolically and energetically expensive; thus, under physiological conditions, intermediates of purine degradation are efficiently reused through salvage pathways. Excess purines are oxidized and eliminated via the kidneys and intestine. The efficient elimination of excess purines in humans is critical because the primary waste product of purine metabolism, uric acid, is proinflammatory and has been linked to multiple health conditions. Recent studies suggest that gut bacteria influence the purine pool locally and systemically. Bacteria can break down uric acid and other purines aerobically and anaerobically and may regulate their homeostasis. In this article, we provide an overview of purines and their metabolism, and we discuss our current understanding of the complex purine-dependent cross talk and cross-feeding between the host and the gut microbiome.
Microbial Enzymes for Biomass Conversion
Plant biomass has emerged as a cornerstone of the global bioenergy landscape because of its abundance and cost-effectiveness. The cell wall of plant biomass is an intricate network of cellulose, hemicellulose, and lignin. The hydrolysis of cellulose and hemicellulose by holoenzymes converts these polymers into monosaccharides and paves the way for the production of bioethanol and other bio-based products. This enzymatic and fermentative process is crucial for the sustainable use of agro-industrial residues as renewable energy sources, reducing reliance on fossil fuels and lowering greenhouse gas emissions. This review explores critical aspects of lignocellulolytic enzyme systems, all of which derive from microorganisms. Furthermore, it underscores the advantages of microbial sources and their potential for enhancing enzyme properties through genetic engineering and enzyme immobilization.
Making Fungal-Photobiont Symbioses in the Lab: Past, Present, and Future of the Elusive In Vitro Lichen
The ability to synthesize lichen symbioses in vitro from pure cultures of transformable symbionts would be a game changer for experiments to identify the metabolic interplay that underpins the success of lichens. However, despite multiple reports of successful lichen resynthesis, no lichen lab model system exists today. We reviewed 150 years of in vitro lichen studies and found that the term resynthesis is applied to many types of fungal-photobiont cocultures that do not resemble lichens. Some of the most lichen-like results, for their part, were obtained from nonaxenic tissue culture. Only a few studies reported obtaining natural-looking lichens from axenic input cultures, but all appear to have been isolated successes obtained against the background of extensive contamination. We suggest revisiting resynthesis experiments in light of recent advances in our understanding of lichen microbial composition to test whether in vitro lichen morphogenesis requires microbial inputs beyond those of the canonical fungal and algal symbionts.
Marine Bacterial Biofilms: Shaping Surface Communities
The assembly of marine benthic communities has become a focal point in marine ecology. We address how the bottom layers of benthic communities (i.e., the microbes inhabiting the basal biofilm) influence the complex accumulation of eukaryotes that grow on top of them. Specifically, we discuss () what organisms make up benthic biofilms, what brings about their attachment to surfaces, and how they vary in space and time; () what eukaryotic organisms are in marine benthic communities, how they vary in space and time, and the nature of microbial cues that bring about their recruitment to particular benthic sites; () the roles of bacterial-animal symbiosis in the composition of benthic communities; () what is happening to biofilms and their roles as habitat engineers in the rapidly changing world; and () how the geological history of bacteria and microbial mats on the ocean floor powerfully influenced the evolution of larval-bacterial interactions.
Decoding Microbial Community Assembly: Insights on Vectors of Infectious Diseases
Vector-borne diseases (VBDs), which are caused by pathogens transmitted by vectors such as mosquitoes and ticks, account for more than 17% of infectious diseases and more than 700,000 deaths annually. The complexity of VBDs arises from ecological interactions among hosts, vectors, pathogens, and the environment, with vector microbiota playing a pivotal role in the modulation of vector competence. Advances in sequencing and in microbiome analysis have deepened our understanding of microbial community assembly within vectors and revealed opportunities for novel control strategies. Network analysis has become essential for uncovering microbial interactions and identifying keystone species that affect community stability and pathogen transmission. Despite progress, key challenges remain in deciphering the drivers of vector microbiota assembly. This review highlights factors shaping microbiota assembly, the potential of network analysis, and promising interventions such as antimicrobiota vaccines and paratransgenesis to reduce pathogen transmission. Future research should focus on standardizing methodologies and leveraging emerging technologies for effective and sustainable VBD control.
A Comparative Analysis: Molecular Mechanisms of Carbon Catabolite Repression in Bacteria
In the environment, bacteria often encounter a mixture of different carbon sources (C-sources) that can potentially be used. However, their uptake and utilization are selective and controlled in a hierarchical order by a complex regulatory pathway named carbon catabolite repression (CCR). Currently, two major types of CCR mechanisms have been described: () In (formerly ) and , CCR depends on the phosphorylation state of the components of the phosphoenolpyruvate-sugar phosphotransferase system (PTS) and their subsequent regulatory activity, and () in pseudomonads, transcripts under CCR control are repressed by the posttranscriptional regulators Hfq and Crc. The repressive effect is antagonized by Hfq- and Crc-titrating RNAs (e.g., CrcZ, CrcY, and CrcX) that are expressed in response to the preference for C-sources. In addition, the importance of CCR as a sensor linking carbon availability with the regulation of virulence, chemotaxis, quorum sensing, and antibiotic susceptibility is addressed in this article.
Prokaryotic Circadian Systems: Cyanobacteria and Beyond
Circadian clocks are biological timekeeping mechanisms that synchronize physiology with the 24-h day-night cycle and provide temporal order to cellular events that recur daily as circadian rhythms. The cyanobacterium displays robust circadian rhythms and for more than 30 years has served as a model organism for uncovering the principles of prokaryotic timekeeping. The fundamental driving force behind these rhythms is a three-protein oscillator composed of KaiA, KaiB, and KaiC. In this review, we summarize current knowledge of the molecular mechanism of the Kai oscillator and focus on the dynamic conformational changes of these proteins over the period of a day. We also discuss how timing information is relayed from the oscillator to regulate downstream gene expression, thereby influencing cellular physiology. Furthermore, we explore circadian or circadian-like timing systems identified in other prokaryotes. We hope this review can inspire the discovery of new clock mechanisms in the microbial world and beyond.
Temperature as a Driver of Phage Ecology and Evolution
Bacteriophages (phages) are virtually ubiquitous and play a fundamental role in the ecological and evolutionary dynamics of their bacterial hosts. While phages are found across many thermal environments, they can be highly sensitive to changes in temperature. Moreover, phages are expected to face increasingly frequent and intense thermal perturbations with global climate change. In this review, we combine theoretical and empirical evidence to assess the impact of the thermal environment on phage biology at the global scale. We identify key thermal environments that phages inhabit, and we discuss the role of temperature in determining phage life-history strategies, ecological interactions, and evolutionary dynamics. We then explore the potential effects of thermal variation on phage functions in natural microbial communities and the application of phages as biomedical therapeutics.
Commensal and Antimicrobial-Resistant Gonorrhea
Alongside the crisis of antimicrobial-resistant gonorrhea is the threat of bystander selection on commensal . As species are permissive to gene flow across lineages, their evolutionary fates are irrevocably intertwined. Horizontal gene transfer (HGT) within the genus occurs through transformation and exchange of plasmids through conjugation. Both mechanisms of HGT threaten the long-term efficacy of antimicrobial treatments, with resistance passed between commensals and pathogens multiple times (e.g., mosaic and alleles). Here, we underscore the importance of commensal as a bubbling cauldron of adaptive solutions for pathogenic , review the mechanisms of resistance harbored by commensals and transferred to the gonococcus, and discuss the impact of contemporary selective pressures on the future evolutionary trajectory of the genus. Ultimately, we believe that predicting the future efficacy of antimicrobials for the treatment of gonorrhea will only be successful if the commensal are also considered.
Pathogenic Fungal Sensing and Responses to Stressful Host Environments
Despite the ubiquity of fungi in nature, only a small fraction are pathogenic to humans, and the majority of these fungi are opportunistic and affect immunocompromised individuals. In general, pathogen emergence is restricted by the ability of fungi to sense and withstand human host environmental cues and stresses. These stress responses in fungi involve immediate survival reactions as well as long-term adaptations. Additionally, some opportunistic pathogenic behavior suggests that virulence traits evolved for environmental survival, a concept known as exaptation. This review covers recent advances in examining fungal responses to host environments and focuses on stress pathways including HOG (high osmolarity glycerol) and CWI (cell wall integrity), thermotolerance mechanisms, CO and oxygen sensing, nutrient and metal stresses, pH adaptation, and antimicrobial defenses. By focusing on both conserved and specialized responses, we highlight the critical role of stress adaptation in pathogenicity and potential avenues for further research and therapeutic intervention.
The Antimicrobial and Host Defense Peptides of
fruit flies are a powerful model for studying innate immunity. In , seven classical antimicrobial peptide (AMP) gene families were identified in the 1990s. These genes are primarily regulated by the TOLL and IMD NF-κB pathways in response to infection. Analyses of mutants have revealed their important roles, including a surprising degree of peptide-microbe specificity at the effector level, in the host defense against gram-negative bacteria and fungi. Many new families of host defense peptides (HDPs) with unknown mechanisms of action are now being investigated. One prominent example is the Bomanins, which are peptides with an essential role in combatting infection by practically all gram-positive bacteria and fungi. Recent studies suggest that AMPs may have broader roles beyond direct antimicrobial activity, notably in the brain and behavior. This review summarizes what is known about each family of HDPs and provides supplementary discussion for less characterized genes involved in defense against infection.
Circadian Biology in Parasites: Beyond Known Mechanisms
Circadian rhythms play a fundamental role in regulating biological processes across the tree of life. While these 24-h cycles are well-characterized in model organisms, their role in parasitic organisms has remained largely unexplored until recently. Here, we review emerging evidence that parasites possess intrinsic timekeeping abilities, focusing particularly on the malaria parasite . We examine two principal paradigms of biological timing: transcriptional-translational feedback loops and posttranscriptional feedback loops. Despite lacking canonical clock genes found in other eukaryotes, employs sophisticated regulatory machinery, including ApiAP2 transcription factors, chromatin regulators, and noncoding RNAs, that could form novel timing circuits. We discuss how these mechanisms might enable parasites to synchronize with host rhythms and optimize their development and transmission. Understanding these temporal regulatory networks could reveal new therapeutic strategies and expand our knowledge of biological timing mechanisms across evolution.
Carbon Metabolism of Intracellular Parasitic Protists
Apicomplexan and trypanosomatid parasites cause important human diseases, including malaria, toxoplasmosis, Chagas disease, and human leishmaniasis. The mammalian-infective stages of these parasites colonize nutrient-rich, intracellular niches in a range of different host cells. These niches include specialized vacuoles ( spp., ), the mature lysosome of phagocytic cells (), and the cytoplasm of nucleated host cells (). Here, we review the different growth and metabolic strategies utilized by each of these protists to survive in these niches. Although all stages utilize sugars as preferred carbon sources, different species or developmental stages vary markedly in their dependence on aerobic fermentation versus respiratory metabolism and their co-utilization of other carbon sources. Stage-specific differences in glycolytic and mitochondrial respiratory capacity may be a hardwired feature of each stage and reflect the trade-off of achieving high growth rates at the expense of host range adaptability and establishing long-lived persistent infections.
Mutagenesis: Insights from Single-Cell, Real-Time Approaches
All genetic variation fueling evolution depends on mutations. Although mutations have been extensively studied for almost a century, until a decade ago the investigation of mutations was limited to population-level analysis. This constraint has hampered the exploration of cellular heterogeneity in mutation processes and its evolutionary implications. To overcome these limitations, quantitative visualization methods for studying mutations in the bacterium at the single-cell level have been developed. These approaches offer the possibility of accessing a major source of mutations, DNA polymerase errors, and their fate, i.e., repair versus conversion to mutation. In addition, such methods allow for quantitative characterization of the effects of mutations on cell fitness. This article discusses insights into the mutation process derived from these new single-cell mutagenesis approaches.
Non-Conventional Yeasts as a Source of Genetic Diversity and Biotechnological Potential
Most of our current knowledge about yeast is based on the workhorse . However, can this yeast represent the vast array of natural yeast life-forms? This review discusses significant recent advances in the study of non- yeasts, also known as non-conventional yeasts (NCYs). We () review recent literature on bioprospecting methodologies and on population genomics that have expanded our understanding of NCY diversity, () highlight critical species with industrial applications, and () offer insights into how NCYs' genetic diversity translates into phenotypic plasticity and adaptation to extreme environments. We assess the limitations that are delaying the widespread use of NCYs in biotechnology, including the need for ambitious bioprospecting efforts and robust genetic tools in the scaling up of NCY-based processes for industry. NCYs could offer novel sustainable solutions in the food, beverage, pharmaceutical, and bioenergy sectors and could open a new frontier of commercial opportunities.
Why Do Filamentous Produce Such a Vast Array of Specialized Metabolites?
Bacteria of the phylum are extremely diverse: They inhabit niches ranging from soils and ocean sediments to the normal human microbiota, and they cause tuberculosis, one of the most prevalent chronic bacterial infections. They display an accordingly wide range of adaptive traits that enable their persistence, including, in some clades, a vast repertoire of biologically active small molecules. While humans have capitalized on this trove of useful natural products (also called secondary or specialized metabolites), the utility of these molecules for their producers has been challenging to directly assess. In this review, we consider adaptations that may have paved the way for the evolution of the expansive specialized metabolisms present in certain clades of . We also consider the evolutionary pressures that may have driven diversification of these metabolisms and document how these organisms use these molecules in microbial interactions.
Kin Recognition Systems and Their Role in Multicellular Behaviors
Interactions between individuals are at the foundation of every community. Furthermore, multicellular behaviors can emerge when individuals come together. Microbes-bacteria, fungi, archaea, and parasites-can engage in multicellular behaviors, which help with population dispersal, infections, and protection from environmental threats. A critical interaction in collectives is determining whether the interacting neighbor is a sibling (kin) or a nonsibling (nonkin). Multiple molecular ways exist to achieve kin recognition and discrimination, especially when fitness is essential. This review considers four bacterial and eukaryotic microorganisms that engage in collective migration and where recognition is known or implied as part of their emergent behavior. This comparative analysis considers shared themes about recognition behaviors among these social microbes, as well as open questions. As more is learned about why kin recognition occurs in different species, a greater understanding will emerge about its evolutionary history and the potential for exogenous control of microbial social groups.
Horizontal Gene Transfer and Recombination in Cyanobacteriota
Cyanobacteria played a pivotal role in shaping Earth's early history and today are key players in many ecosystems. As versatile and ubiquitous phototrophs, they are used as models for oxygenic photosynthesis, nitrogen fixation, circadian rhythms, symbiosis, and adaptations to harsh environments. Cyanobacterial genomes and metagenomes exhibit high levels of genomic diversity partly driven by gene flow within and across species. Processes such as recombination and horizontal transfer of novel genes are facilitated by the mobilome that includes plasmids, transposable elements, and bacteriophages. We review these processes in the context of molecular mechanisms of gene transfer, barriers to gene flow, selection for novel traits, and auxiliary metabolic genes. Additionally, Cyanobacteriota are unique because ancient evolutionary innovations, such as oxygenic photosynthesis, can be corroborated with fossil and biogeochemical records. At the same time, sequencing of extant natural populations allows the tracking of recombination events and gene flow over much shorter timescales. Here, we review the challenges of assessing the impact of gene flow across the whole range of evolutionary timescales. Understanding the tempo and constraints to gene flow in Cyanobacteriota can help decipher the timing of key functional innovations, analyze adaptation to local environments, and design Cyanobacteriota for robust use in biotechnology.
Evolution and Ecology of
are among the most well-studied and important groups of bacteria, largely owing to their prolific production of biomedically important compounds like antibiotics and antifungals. Research over more than a half-century has elucidated the molecular and mechanistic details of multicellular development and the production of secondary metabolites. In contrast, the evolutionary and ecological mechanisms that underlie these phenotypes are comparatively understudied. Our aim in this review is to examine these aspects of biology, with a focus on the benefits associated with their complex life cycle, their multicellular architecture and development, and their production of antibiotics. In addition to highlighting existing studies, we point to clear knowledge gaps that can serve to motivate further research on these bacteria. A greater understanding of evolution and ecology is needed to improve our ability to exploit these organisms for biomedical and agricultural applications.
