Search

Many microbes in nature reside in dense, metabolically interdependent communities. We investigated the nature and extent of microbe-virus interactions in relation to microbial density and syntrophy by examining microbe-virus interactions in a biomass dense, deep-sea hydrothermal mat. Using metagenomic sequencing, we find numerous instances where phylogenetically distant (up to domain level) microbes encode CRISPR-based immunity against the same viruses in the mat. Evidence of viral interactions with hosts cross-cutting microbial domains is particularly striking between known syntrophic partners, for example those engaged in anaerobic methanotrophy. These patterns are corroborated by proximity-ligation-based (Hi-C) inference. Surveys of public datasets reveal additional viruses interacting with hosts across domains in diverse ecosystems known to harbour syntrophic biofilms. We propose that the entry of viral particles and/or DNA to non-primary host cells may be a common phenomenon in densely populated ecosystems, with eco-evolutionary implications for syntrophic microbes and CRISPR-mediated inter-population augmentation of resilience against viruses.

Deciphering the relationship between a gene and its genomic context is fundamental to understanding and engineering biological systems. Machine learning has shown promise in learning latent relationships underlying the sequence-structure-function paradigm from massive protein sequence datasets. However, to date, limited attempts have been made in extending this continuum to include higher order genomic context information. Evolutionary processes dictate the specificity of genomic contexts in which a gene is found across phylogenetic distances, and these emergent genomic patterns can be leveraged to uncover functional relationships between gene products. Here, we trained a genomic language model (gLM) on millions of metagenomic scaffolds to learn the latent functional and regulatory relationships between genes. gLM learns contextualized protein embeddings that capture the genomic context as well as the protein sequence itself and encode biologically meaningful and functionally relevant information (e.g., enzymatic function, taxonomy). Our analysis of the attention patterns demonstrates that gLM is learning co-regulated functional modules (i.e., operons). Our findings illustrate that gLM's unsupervised deep learning of the metagenomic corpus is an effective and promising approach to encode functional semantics and regulatory syntax of genes in their genomic contexts and uncover complex relationships between genes in a genomic region.

The binding ability of lectins has gained attention owing to the carbohydrate-specific interactions of these proteins. Such interactions can be applied to diverse fields of biotechnology, including the detection, isolation, and concentration of biological target molecules. The physiological aspects of the lectin concanavalin A (ConA) have been intensively studied through structural and functional investigations. X-ray crystallography studies have proven that ConA has two β-sheets and a short α-helix and that it exists in the form of a metalloprotein containing Mn2+ and Ca2+. These heterometals are coordinated with side chains located in a metal-coordinated domain (MCD), and they affect the structural environment in the carbohydrate-binding domain (CBD), which interacts with carbohydrates through hydrogen bonds. Recent studies have shown that ConA can regulate biophysical interactions with glycoproteins in virus envelopes because it specifically interacts with diverse polysaccharides through its CBD (Tyr, Asn, Asp, and Arg residues positioned next to the MCD). Owing to their protein–protein interaction abilities, ConA can form diverse self-assembled complexes including monomers, dimers, trimers, and tetramers, thus affording unique results in different applications. In this regard, herein, we present a review of the structural modifications in ConA through metal-ion coordination and their effect on complex formation. In recent approaches, ConA has been applied for viral protein detection, on the basis of the interactions of ConA. These aspects indicate that lectins should be thoroughly investigated with respect to their biophysical interactions, for avoiding unexpected changes in their interaction abilities.

By facilitating electron transfer to the hydroxylase diiron center, MMOR-a reductase-serves as an essential component of the catalytic cycle of soluble methane monooxygenase. Here, the X-ray structure analysis of the FAD-binding domain of MMOR identified crucial residues and its influence on the catalytic cycle.

The hydroxylation of methane (CH

By facilitating electron transfer to the hydroxylase diiron center, MMOR-a reductase-serves as an essential component of the catalytic cycle of soluble methane monooxygenase. Here, the X-ray structure analysis of the FAD-binding domain of MMOR identified crucial residues and its influence on the catalytic cycle.

Background: The hyperarid core of the Atacama Desert is an extremely harsh environment thought to be colonized by only a few heterotrophic bacterial species. Current concepts for understanding this extreme ecosystem are mainly based on the diversity of these few species, yet a substantial area of the Atacama Desert hyperarid topsoil is covered by expansive boulder accumulations, whose underlying microbiomes have not been investigated so far. With the hypothesis that these sheltered soils harbor uniquely adapted microbiomes, we compared metagenomes and geochemistry between soils below and beside boulders across three distantly located boulder accumulations in the Atacama Desert hyperarid core. Results: Genome-resolved metagenomics of eleven samples revealed substantially different microbial communities in soils below and beside boulders, despite the presence of shared species. Archaea were found in significantly higher relative abundance below the boulders across all samples within distances of up to 205 km. These key taxa belong to a novel genus of ammonia-oxidizing Thaumarchaeota, Candidatus Nitrosodeserticola. We resolved eight mid-to-high quality genomes of this genus and used comparative genomics to analyze its pangenome and site-specific adaptations. Ca. Nitrosodeserticola genomes contain genes for ammonia oxidation, the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway, and acetate utilization indicating a chemolithoautotrophic and mixotrophic lifestyle. They also possess the capacity for tolerating extreme environmental conditions as highlighted by the presence of genes against oxidative stress and DNA damage. Site-specific adaptations of the genomes included the presence of additional genes for heavy metal transporters, multiple types of ATP synthases, and divergent genes for aquaporins. Conclusion: We provide the first genomic characterization of hyperarid soil microbiomes below the boulders in the Atacama Desert, and report abundant and highly adapted Thaumarchaeaota with ammonia oxidation and carbon fixation potential. Ca. Nitrosodeserticola genomes provide the first metabolic and physiological insight into a thaumarchaeal lineage found in globally distributed terrestrial habitats characterized by various environmental stresses. We consequently expand not only the known genetic repertoire of Thaumarchaeota but also the diversity and microbiome functioning in hyperarid ecosystems. Conclusion: We provide the first genomic characterization of hyperarid soil microbiomes below the boulders in the Atacama Desert, and report abundant and highly adapted Thaumarchaeaota with ammonia oxidation and carbon fixation potential. Ca. Nitrosodeserticola genomes provide the first metabolic and physiological insight into a thaumarchaeal lineage found in globally distributed terrestrial habitats characterized by various environmental stresses. We consequently expand not only the known genetic repertoire of Thaumarchaeota but also the diversity and microbiome functioning in hyperarid ecosystems.

The hyperarid core of the Atacama Desert is an extremely harsh environment previously thought to be colonized by only a few heterotrophic bacterial species. In addition, carbon and nitrogen cycling in these highly oligotrophic ecosystems are poorly understood. Here we genomically resolved a novel genus of Thaumarchaeota, Ca. Nitrosodesertus, found below boulders of the Atacama hyperarid core, and used comparative genomics to analyze their pangenome and site-specific adaptations. Their genomes contain genes for ammonia oxidation and the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway, indicating a chemolithoautotrophic lifestyle. Ca. Nitrosodesertus possesses the capacity for tolerating extensive environmental stress highlighted by the presence of genes against oxidative stress, DNA damage and genes for the formation of biofilms. These features are likely responsible for their dominance in samples with extremely low water content across three different boulder fields and eight different boulders. Genome-specific adaptations of the genomes included the presence of additional genes for UV resistance, heavy metal transporters, multiple types of ATP synthases, and divergent genes for aquaporins. Our results suggest that Thaumarchaeota mediate important carbon and nitrogen cycling in the hyperarid core of the Atacama and are part of its continuous and indigenous microbiome.

The existence of microbial activity hotspots in temperate regions of Earth is driven by soil heterogeneities, especially the temporal and spatial availability of nutrients. Here we investigate whether microbial activity hotspots also exist in lithic microhabitats in one of the most arid regions of the world, the Atacama Desert in Chile. While previous studies evaluated the total DNA fraction to elucidate the microbial communities, we here for the first time use a DNA separation approach on lithic microhabitats, together with metagenomics and other analysis methods (i.e., ATP, PLFA, and metabolite analysis) to specifically gain insights on the living and potentially active microbial community. Our results show that hypolith colonized rocks are microbial hotspots in the desert environment. In contrast, our data do not support such a conclusion for gypsum crust and salt rock environments, because only limited microbial activity could be observed. The hypolith community is dominated by phototrophs, mostly Cyanobacteria and Chloroflexi, at both study sites. The gypsum crusts are dominated by methylotrophs and heterotrophic phototrophs, mostly Chloroflexi, and the salt rocks (halite nodules) by phototrophic and halotolerant endoliths, mostly Cyanobacteria and Archaea. The major environmental constraints in the organic-poor arid and hyperarid Atacama Desert are water availability and UV irradiation, allowing phototrophs and other extremophiles to play a key role in desert ecology.

Objective: Staphylococcal scalded skin syndrome (SSSS) is a relatively rare superficial blistering skin disease caused by exfoliating toxins produced by Staphylococcus aureus. We experienced a 3-month outbreak of neonatal SSSS in a maternal unit. Methods: The medical records of newborns who were diagnosed with SSSS were retrospectively reviewed. Results: Eleven newborns with SSSS were transferred to our hospital between January and March 2019. The median age of the newborns was 18.0 (11.0-22.5) days. Of the 11 newborns, 2 (18%) showed the generalized type of SSSS, 4 (36%) the intermediate type, and 5 (45%) the abortive type. S. aureus was isolated in 10 of the newborns and found to be methicillin-resistant in 9 cases. All the newborns were treated with intravenous cefazolin, and two newborns with the generalized type were also treated with clindamycin. The median duration of antibiotic use is 8 (6-14) days. All the newborns responded well to antibiotics and were discharged without complications. Conclusion: We recently experienced an outbreak of neonatal SSSS. To manage problems associated with such an outbreak, periodic monitoring is required, along with guidelines for infection control, such as thorough infection education, isolation of infected newborns, and antiseptic handwashing.

DW2008 is an anhydrous ethanol extract of Justicia procumbens produced by Dong-Wha Pharmaceutical, Inc., Co. as a candidate anti-asthmatic drug. In this study, DW2008 selectively reduced T helper 2 (Th2) cytokines in mouse splenocytes and ameliorated ovalbumin-induced airway inflammation by downregulating pulmonary infiltration of differential inflammatory cells and Th2 cytokines more than a decoction or ethanol extract of J. procumbens did in a mouse asthma model. DW2008 also significantly inhibited airway hyperresponsiveness and reduced the thickness of the airway epithelium. HPLC analysis showed that the major peaks (justicidin A and B) of DW2008 were higher than those of the other extracts. Justicidin A and B significantly suppressed Th2 cytokine levels in mouse spleen cells and exhibited a protective effect in ovalbumin-induced airway inflammation. Our findings indicate that DW2008 effectively inhibits allergic airway inflammatory reactions and airway hyperresponsiveness in a mouse model of asthma, suggesting its potential as an anti-asthmatic agent.

Neuronal SNARE proteins mediate neurotransmitter release at the synapse by facilitating the fusion of vesicles to the presynaptic plasma membrane. Cognate v-SNAREs and t-SNAREs from the vesicle and the plasma membrane, respectively, zip up and bring about the apposition of two membranes attached at the C-terminal ends. Here, we demonstrate that SNARE zippering can be modulated in the midways by wedging with small hydrophobic molecules. Myricetin, which intercalated into the hydrophobic inner core near the middle of the SNARE complex, stopped SNARE zippering in motion and accumulated the trans -complex, where the N-terminal region of v-SNARE VAMP2 is in the coiled coil with the frayed C-terminal region. Delphinidin and cyanidin inhibited N-terminal nucleation of SNARE zippering. Neuronal SNARE complex in PC12 cells showed the same pattern of vulnerability to small hydrophobic molecules. We propose that the half-zipped trans -SNARE complex is a crucial intermediate waiting for a calcium trigger that leads to fusion pore opening.

There are tremendous drug candidates that suffer from insolubility in water. In the present study, it is shown that Coenzyme Q10 (CoQ10), a model water-insoluble compound, can be nanoparticulated into a water-soluble form using apolipoprotein A-I (apoA-I). Similar to the way that apoA-I forms nascent discoidal high density lipoprotein (ndHDL) particles by bordering acyl chain tails of phospholipids, CoQ10 could be enclosed into the circle of a disk made of apoA-Is. The resulting nanostructure of CoQ10 and apoA-I was water-soluble with a size of approximately 12 nm in diameter and was physically more robust than liposome. We expect that the strategy suggested in this study can be exploited to assemble nano-sized, water-soluble structures of various water-insoluble drug candidates.