FEMS microbiology reviews最新文献

Type IV secretion systems (T4SS) are versatile nanomachines responsible for the transfer of DNA and proteins across cell envelopes. From their ancestral role in conjugation, these systems have diversified into a superfamily with functions ranging from horizontal gene transfer to the delivery of toxins to eukaryotic and prokaryotic hosts. Recent structural and functional studies have uncovered unexpected architectural variations not only among Gram-negative systems but also between Gram-negative and Gram-positive systems. Despite this diversity, a conserved set of core proteins is maintained across the superfamily. To facilitate cross-system comparisons, we propose in this review a unified nomenclature for conserved T4SS subunits found in both Gram-negative and Gram-positive systems. We further highlight conserved and divergent mechanistic and architectural principles across bacterial lineages, and we discuss the diversity of emerging T4SSs whose unique structures and functions expand our understanding of this highly adaptable secretion superfamily.

Two-component systems (TCSs), the primary communication pathways in bacteria, are comprised of two proteins: a signal-sensing histidine kinase (HK) and an output-generating response regulator (RR). Classically, individual TCSs have been viewed as simple input-output systems, in which signal propagate via phosphorylation from the HK to the cognate RR, the latter triggering downstream functions. Emerging evidence suggests that TCSs can also operate through intricate networks, collectively sensing multiple inputs and generating fine-tuned, concerted, diversified, and complex outputs, modulated by several factors such as TCS-dependent cross-talk, additional layers of posttranslational modifications, external protein-based signalling input or adaptor molecules, and small RNAs. In this review, using evidence from mycobacterial TCSs, we discuss how TCSs can function as multiple input-multiple output (MIMO) hubs, thereby serving as signal integration and dispersion units to generate complex adaptive responses tuned by many modulating factors. We also discuss how the MIMO landscape of TCSs drives bacterial adaptation and presents potential strategies for therapeutic intervention.

Staphylococcus aureus is a Gram-positive bacterium capable of infecting multiple types of cells, organs, and tissues in the human body. Treatment can become highly challenging, especially in the case of intracellular infections and upon biofilm formation. Additionally, this pathogen has developed several antimicrobial resistance mechanisms, and resistant strains such as methicillin-resistant S. aureus (MRSA) are among the most difficult to treat. Within this context, nanomedicine can offer novel and more efficient treatments against S. aureus. Here, we first introduce the challenges in the treatment of S. aureus infections, focusing on intracellular infections and biofilms, and challenges associated with the development of resistance. We then provide an overview of the multiple applications of nanomedicine against S. aureus infection and discuss how nanomedicine may overcome the challenges in reaching this pathogen and eliminating it, including potential solutions less prone to generating resistance. Finally, we discuss the current clinical development of antimicrobial nanomedicines, where only one out of 35 completed trials has so far targeted MRSA, indicating that most research is still at the preclinical stage. Challenges in the clinical translation of antimicrobial nanomedicines are discussed, together with strategies to support the development of these promising therapeutic agents.

Retroviruses are exclusive group of positive-sense RNA viruses defined by their ability to reverse transcribe their RNA genome and integrate it into the host's chromosomal DNA. This distinctive replication strategy enables persistent infection and has profoundly shaped our understanding of molecular biology, gene regulation, and evolution. Retroviruses have contributed to landmark discoveries, including the identification of oncogenes, mechanisms of transcriptional control, and the development of gene therapy vectors. This review provides an updated overview of retroviral molecular biology, emphasizing the coordinated steps of the viral life cycle and emerging insights that are reshaping classical models. It explores virion structure, genome organization, and the interplay of cis-acting sequences and trans-acting factors that govern replication. Special focus is given to recent advances in understanding nuclear trafficking of capsids, spatial dynamics of reverse transcription and integration leading to provirus formation, RNA nuclear export, and selective genome packaging. The structural and functional roles of viral proteins, particularly Gag, are discussed in the context of assembly and maturation. By integrating foundational concepts with new discoveries, this review highlights the molecular sophistication of retroviral replication and identifies outstanding questions that guide future research, with implications extending to antiviral strategies, gene therapy, cancer biology, and evolution.

Metabolomics, a critical tool for analyzing small-molecule metabolites, integrates with genomics, transcriptomics, and proteomics to provide a systems-level understanding of fungal biology. By mapping metabolic networks, it elucidates regulatory mechanisms driving physiological and ecological adaptations. In fungal pathogenesis, metabolomics reveals host-pathogen dynamics, identifying virulence factors like gliotoxin in Aspergillus fumigatus and metabolic shifts, such as glyoxylate cycle upregulation in Candida albicans. Ecologically, it highlights fungal responses to abiotic stressors, including osmolyte production like trehalose, enhancing survival in extreme environments. These insights highlight metabolomics' role in decoding fungal persistence and niche colonization. In drug discovery, it aids target identification by profiling biosynthetic pathways, supporting novel antifungal and nanostructured therapy development. Combined with multi-omics, metabolomics advances insights into fungal pathogenesis, ecological interactions, and therapeutic innovation, offering translational potential for addressing antifungal resistance and improving treatment outcomes for fungal infections. Its progress shed light on complex fungal molecular profiles, advancing discovery and innovation in fungal biology.

Electrical signaling is a fundamental mechanism for integrating environmental stimuli and coordinating responses in living organisms. While extensively studied in animals and plants, the role of electrical signaling in fungi remains a largely underexplored field. Early studies suggested that filamentous fungi generate action potential-like signals and electrical currents at hyphal tips, yet their function in intracellular communication remained unclear. Renewed interest in fungal electrical activity has fueled developments such as the hypothesis that mycorrhizal networks facilitate electrical communication between plants and the emerging field of fungal-based electronic materials. Given their continuous plasma membrane, specialized septal pores, and insulating cell wall structures, filamentous fungi possess architectural features that could support electrical signaling over long distances. However, studying electrical phenomena in fungal networks presents unique challenges due to the microscopic dimensions of hyphae, the structural complexity of highly modular mycelial networks, and the limitations of traditional electrophysiological methods. This review synthesizes current evidence for electrical signaling in filamentous fungi, evaluates methodological approaches, and highlights experimental challenges. By addressing these challenges and identifying best practices, we aim to advance research in this field and provide a foundation for future studies exploring the role of electrical signaling in fungal biology.

Purine-based metabolites serve as essential mediators of signaling, immunity, and host-microbe interactions across biological kingdoms. This review explores their extracellular and intracellular functions, focusing on well-characterized molecules as well as emerging players, and examines the conserved and divergent mechanisms underlying purine-mediated responses in plants and animals, with comparative insights into microbial strategies that influence or exploit these pathways. Key topics include the role of extracellular adenosine triphosphate in immune responses, the dual function of NAD+ as both a metabolic cofactor and signaling molecule, and the emerging roles of deoxynucleosides and cyclic nucleotides in stress and immunity regulation. Special emphasis is placed on Toll/interleukin-1 receptor (TIR) domain-containing proteins, which generate novel purine-derived infochemicals-bioactive signaling metabolites that regulate immune responses and cell death while modulating host-microbe interactions. By integrating insights across biological kingdoms, this review underscores the potential of purine-based signaling molecules and their natural and chemically modified functional derivatives as targets for therapeutic and agricultural innovation, bridging fundamental discoveries with practical applications. Finally, moving beyond purine-based metabolites, we offer a new perspective on immunometabolism and infochemicals as fundamental regulators of host-microbe interactions, shaping defense, modulating metabolism, facilitating symbiosis, and driving broader evolutionary dynamics.

Cable bacteria are a unique type of filamentous microorganism that can grow up to centimetres long and are capable of long-distance electron transport over their entire lengths. Due to their unique metabolism and conductive capacities, the study of cable bacteria has required technical innovations, both in adapting existing techniques and developing entirely new ones. This review discusses the existing methods used to study eight distinct aspects of cable bacteria research, including the challenges of culturing them in laboratory conditions, performing physical and biochemical extractions, and analysing the conductive mechanism. As cable bacteria research requires an interdisciplinary approach, methods from a range of fields are discussed, such as biogeochemistry, genomics, materials science, and electrochemistry. A critical analysis of the current state of each approach is presented, highlighting the advantages and drawbacks of both commonly used and emerging methods.

Helminths are highly prevalent in many regions of the world. Due to the chronic nature of most helminth infections, these parasites are proficient immunomodulators of their hosts. This modulation often leads to skewed or even impaired immune responses against unrelated antigens, such as viruses and vaccines, which can be both beneficial and detrimental for the host. The extent of these effects and the impact on the outcomes of viral infection depends on a variety of factors including timing and tropism of both infections, pathological mechanisms, genetic background, and environmental factors. In this review, we dissect these complex interactions between virus and helminths in the context of coinfection and the impact of helminth infection on antiviral vaccine efficacy. We characterize the key contributing mechanisms that have been defined in preclinical models and human trials and describe the immune actors involved in the modulation of the antiviral and vaccine immune response by helminths. Finally, we address the limitations of our current understanding of helminth-virus interactions.

Glycolysis stops where gluconeogenesis starts-at pyruvate, the central metabolite of biosynthesis. The early history of carbon metabolism is preserved in archaeal and bacterial enzymes for glucose synthesis and breakdown. Here, we summarize the distribution and phylogeny of enzymes involved in glycolysis, gluconeogenesis, and glycogen metabolism from genomes of cultured prokaryotes. The presence of glycolytic pathways in H2-dependent chemolithoautotrophs, including methanogens, which cannot grow on exogenous glucose, correlates with their use of glycogen for intracellular carbon storage. Glycogen synthesis and gluconeogenesis are universal among prokaryotes, but glycolysis is not, indicating that the enzymatic conversions of glycolysis arose in the gluconeogenic direction encompassing three phases: (1) an autotrophic origin from H2 and CO2 to pyruvate and triosephosphate (trunk glycolysis) fulfilling basic amino acid and cofactor synthesis in the last universal common ancestor, (2) from triosephosphate to glucose supplying cell wall (murein and pseudomurein) and nucleic acid biosynthetic requirements in the first free-living autotrophs, also giving rise to intracellular carbon reserves (glycogen), followed by (3) diversification and transfer of enzymes for glycogen-mobilizing glycolytic routes. An autotrophic origin of trunk glycolysis followed by glycogen-dependent origin of glucose utilization account for conservation, distribution, and diversity of enzymes observed in microbial sugar phosphate pathways.