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Conidiation is the primary mode of reproduction in filamentous fungi and is essential for the dispersal of pathogenic species. However, the fundamental cellular mechanisms regulating conidiation in plant pathogenic fungi remain largely unexplored. Here, using Verticillium dahliae as a model, we investigated the dynamic assembly and function of the contractile actomyosin ring (CAR) and septins during conidiation through live-cell imaging. We show that septins, visualized via VdCdc11-GFP, first accumulate at the tip of budding hyphae during the transition from hyphal elongation to apical budding, and undergo an hourglass-to-double-ring transition at the bud neck. Following mitosis, myosin II and actin assemble simultaneously into a contractile ring to drive cytokinesis. Disruption of core septin function results in defective nuclear segregation and aberrant nuclear migration during mitosis, as well as delayed recruitment of myosin II to the bud neck, indicating that septins scaffold cytokinetic machinery and coordinate nuclear division during conidiation. In contrast, during hyphal septation, myosin II, actin, and septins appear simultaneously as a diffuse cortical band, with septin organization dependent on actin. Collectively, these findings reveal distinct spatial and temporal coordination between actomyosin and septins in two cytokinetic contexts-conidiation and hyphal septation-and define apical budding as a specialized cytokinesis mode in V. dahliae. Our study broadens the understanding of fungal cytokinesis beyond yeast models to multicellular filamentous fungi.

Microorganisms play a vital role in human health through their interactions with the body. Studies of host-microbe mechanisms and interactions are crucial for advancing health management. Recently, the organoid-based models have provided new platforms in this field. Derived from human tissues, these models offer several advantages over traditional systems and, when combined with advanced analytical techniques, they enable deeper insights into host-microbe interactions. In this review, we summarize the different models and techniques used, with a particular focus on the newly developed organoid models. We discuss how these models can be effectively utilized in microorganism-host interaction studies and address their associated limitations.

Dissimilatory sulfite reduction (DSR) has been essential to microbial energy metabolism in the biogeochemical sulfur cycle since the Paleoarchean Era. However, due to the lack of an integrated assessment of geological record and genomic data, the evolutionary origin of DSR remains elusive in terms of time, habitat, and genetic basis. In this study, we reconstructed the evolutionary pathways and the ancestral sequences of Dsr proteins by mining metagenomes ranging from mesothermal to hyperthermal environments. A phylogenetic analysis of the key catalytic enzyme, DsrAB, and other Dsr proteins indicates that the earliest and most basic functional cascade, DsrABCNM, emerged prior to the latest common ancestor of several basal branching DsrAB clusters encoded by bacteria and archaea. Using a molecular dating strategy that calibrates the protein tree with a species tree, we predicted that the DSR originated 3.508 billion years ago (Ga). This finding strongly confirms the earliest geological evidence of DSR ( ~ 3.47 Ga). Further predictions from ancestral sequence reconstruction indicate that the optimal catalytic temperature of DsrA at the time of DSR origin was approximately 73°C, which is consistent with the petrographic and geochemical evidence in early Archean hydrothermal deposits. After its hot origin, DsrA diversified into subclades that adapted to various temperature levels following the Great Oxidation Event. This is exemplified by the evolution of the reductive archaeal-type DsrA. Our results synchronize the molecular ages with the geological record, which advances our understanding of the earliest DSR systems and highlights the enzymatic adaptations of microbial life in the Archean biosphere.

Bacteriophages and archaeal viruses are the most abundant biological entities on Earth. Through a long-standing co-evolutionary arms race, they have driven the emergence of a diverse repertoire of prokaryotic defense systems. This review summarizes these systems, highlighting their diverse antiviral mechanisms across distinct stages of viral infection, from surface barriers and inducible innate responses to specific adaptive defenses, and the intricate interplay between these defense strategies. By examining host-virus counter defense dynamics, the trade-off between survival benefit and adaptive cost, the co-evolution of RNA and protein components, and the comparison with eukaryotic immune systems, we underscore the intrinsic complexity and evolutionary plasticity of prokaryotic antiviral immunity. A deeper understanding of these processes and mechanisms will not only shed light on the origins and evolution of the immune system but also provide valuable opportunities for the development of biotechnological tools.

Tolerance of high hydrostatic pressure (HHP) is the hallmark of deep subsurface microorganisms, while its mechanisms remain under-investigated. This study explores HHP adaptation in the piezotolerant bacterium Orenia metallireducens across its near-full pressure range (0.1-40 MPa). At inhibitory pressure (40 MPa), the organism redirected carbon flux toward more favorable energy generation and biosynthesis using ferric mineral as the "electron sink." Furthermore, both universal and pressure-dependent strategies enabled the organism to withstand varying pressures. These findings highlight the role of iron minerals in microbial HHP adaptation and reveal novel survival strategies, advancing our understanding of deep-life evolution and biogeochemical impacts.

Helicobacter pylori is a major gastric pathogen with increasing antibiotic resistance, creating an urgent need for new therapeutic strategies. We screened 37 pure compounds and 9 herbal extracts for anti-H. pylori activity and identified berberrubine as the most potent agent, with a minimum inhibitory concentration of 11 μg/ml. Berberrubine exhibited bacteriostatic effects by inducing oxidative stress and disrupting membrane integrity, as demonstrated by transcriptomic analysis, reactive oxygen species (ROS) accumulation, and structural damage, all of which were alleviated by the antioxidant N-acetylcysteine. Similar inhibitory effects were observed in Escherichia coli, indicating broader antimicrobial potential. This study provides the mechanistic evidence of berberrubine's activity against H. pylori, highlighting its promise as a candidate for development into alternative therapies to address antibiotic resistance.

The "superbug" Candida auris has been ranked as a priority fungal pathogen and is becoming a serious threat to public health. However, the underlying mechanisms of real-world pathogen-host interactions remain elusive, in part due to the lack of powerful immunocompetent animal models. Here, we report that selected wild-type strains of Drosophila melanogaster can be developed as a promising infection model to recapitulate C. auris systemic infection. The systemic and organ-specific responses to C. auris infection in vivo were evaluated, as well as the corresponding transcriptional profiling. Our findings confirmed that Toll and JAK-STAT signaling pathways mediate antifungal responses in the Drosophila model following C. auris infection. Moreover, we identified certain conserved novel factors required for host-C. auris interactions, highlighting the fly model's potential to reveal subtle immune mechanisms not readily observed in mammalian systems. Taken together, our work demonstrates that wild-type Drosophila offers a robust immunocompetent animal model for further in-depth investigation of dynamic C. auris-host interactions in vivo.

The resistance‒nodulation‒division (RND) family of multidrug efflux transporters is widely distributed in Gram-negative bacteria. Although their roles in mediating antibiotic resistance have been well known, our understanding of how they are altered to augment bacterial adaptation to antibiotic selection remains at an infancy stage. Here, we report the identification of a mutation-based mechanism that empowers the function of the CmeB efflux protein, an RND-type transporter in the zoonotic pathogen Campylobacter. During our surveillance study, we identified Campylobacter isolates that were phenotypically resistant to florfenicol but lacked known florfenicol resistance mechanisms. Using natural transformation and whole genome sequencing, we first linked the phenotype to sequence polymorphisms in the cmeB and subsequently demonstrated that both the T136A and M292I mutations in CmeB are required for the resistance phenotype. The mutations elevated Campylobacter resistance to florfenicol, ciprofloxacin, and other classes of antimicrobial agents. Structural modeling and molecular dynamics simulations revealed that the two residues were localized in the drug-binding pocket of CmeB, and the T136A and M292I substitutions enhanced hydrophobic interactions, stabilized CmeB-antibiotic binding, and lessened steric hindrance in the drug-binding pocket, thereby facilitating antibiotic extrusion by CmeB. Analysis of the Campylobacter genomic sequences deposited in the NCBI database revealed that T136A- and M292I-harboring isolates were found in 35 different countries and associated with various host species, indicating the widespread distribution and clinical relevance of the two mutations. Together, these results identified a new mechanism underlying CmeB-mediated multidrug resistance and provide a potential target for clinical surveillance of antibiotic-resistant Campylobacter.

Bacteria deploy diverse innate immune systems to combat bacteriophage infections. The cyclic-oligonucleotide-based anti-phage signaling system (CBASS) is a type of innate prokaryotic immune system. CBASS synthesizes cyclic-oligonucleotide through cGAS/DncV-like nucleotidyltransferases (CD-NTases) to activate downstream effectors, which kill bacteriophage-infected bacteria, thereby stopping phage spread. One major class of CBASS contains a homolog of eukaryotic ubiquitin-conjugating enzymes, either as an E1-E2 fusion or a single E2 enzyme. Both enzymes function by regulating CD-NTase activity. Currently, many structures of CD-NTases have been reported, but there are only a few reports of structures where CD-NTases form complexes with the associated E2. In this study, we analyzed the length and classification of the CD-NTase in two types of type II CBASS-E1E2/JAB-CBASS and E2-CBASS. We found that the CD-NTase in E2-CBASS is longer and predominantly belongs to clade G. We also present the structure of the SmCdnG-SmE2 complex with the bound GTP substrate, which indicates the conservation of the donor binding pattern. Interestingly, we discovered that SmCdnG contains a conserved C-terminal α-helix and β-sheet structure, which is uniquely involved in forming a complex with SmE2. We also found that the structure of the E2 protein in the E2-CBASS system is highly conserved. Altogether, we provide mechanistic insights into the E2-CBASS system.