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Alcohol intake causes many diseases including neuropsychiatric symptoms, nutritional deficiency, progressive pancreatitis, liver cirrhosis, and ischemic heart disease. The gut microbiota changes significantly after alcohol exposure. Alcohol consumption tends to increase in underage and young people, but the feature of the gut microbiota in puberty remains largely unexplored. In this study, we conducted alcohol-exposed pubertal and adult mice model to investigate the intestinal damage and gut microbiota change. Interestingly, the responses of pubertal mice and adult mice after alcohol exposure were different. We found that alcohol dehydrogenase decreased and aldehyde dehydrogenase increased in the liver of pubertal mice, thus reducing the accumulation of toxic acetaldehyde. Furthermore, alcohol exposure caused less intestinal injury in pubertal mice. Through the analysis of metagenome assembly genome, we obtained many unrecognized bacterial genomes. Limosillactobacillus reuteri (cluster_56) and Lactobacillus intestinalis (cluster_57) were assembled from the samples of pubertal mice, which were involved in the production of indole acetic acid and the transformation of bile acids in response to alcohol exposure. This study provided a new insight to investigate the gut microbiota change and explained the difference of the gut microbiota after alcohol exposure between pubertal mice and adult mice.

Importance: This study elucidates the significant impact of alcohol exposure on the gut microbiota and metabolic pathways in mice, highlighting the differential responses between adolescent and adult stages. Alcohol exposure was found to damage the intestinal barrier, alter the microbial composition by decreasing beneficial bacteria like Lactobacillus, and increase harmful bacteria such as Alistipes. The study also discovered unique microbial changes and resilience in pubertal mice. Species-level metagenomic analysis revealed specific microbial taxa and metabolic functions affected by alcohol. Metagenome-assembled genomes (MAGs) found many species that could not be annotated by conventional methods including many members of Lachnospiraceae, greatly expanding our understanding of the gut microbiota composition. These findings underscore the need for further research on alcohol's effects on various organs and the implications of microbial metabolites on disease progression.

Coral reefs are experiencing unprecedented loss in coral cover due to increased incidence of disease and bleaching events. Thus, understanding mechanisms of disease susceptibility and resilience, which vary by species, is important. In this regard, untargeted metabolomics serves as an important hypothesis-building tool enabling the delineation of molecular factors underlying disease susceptibility or resilience. In this study, we characterize metabolomes of four species of visually healthy stony corals, including Meandrina meandrites, Orbicella faveolata, Colpophyllia natans, and Montastraea cavernosa, collected at least a year before stony coral tissue loss disease reached the Dry Tortugas, Florida, and demonstrate that both symbiont and host-derived biochemical pathways vary by species. Metabolomes of Meandrina meandrites displayed minimal intraspecies variability and the highest biological activity against coral pathogens when compared to other species in this study. The application of advanced metabolite annotation methods enabled the delineation of several pathways underlying interspecies variability. Specifically, endosymbiont-derived vitamin E family compounds, betaine lipids, and host-derived acylcarnitines were among the top predictors of interspecies variability. Since several metabolite features that contributed to inter- and intraspecies variation are synthesized by the endosymbiotic Symbiodiniaceae, which could be a major source of these compounds in corals, our data will guide further investigations into these Symbiodiniaceae-derived pathways.

Importance: Previous research profiling gene expression, proteins, and metabolites produced during thermal stress have reported the importance of endosymbiont-derived pathways in coral bleaching resistance. However, our understanding of interspecies variation in these pathways among healthy corals and their role in diseases is limited. We surveyed the metabolomes of four species of healthy corals with differing susceptibilities to the devastating stony coral tissue loss disease and applied advanced annotation approaches in untargeted metabolomics to determine the interspecies variation in host and endosymbiont-derived pathways. Using this approach, we propose the survey of immune markers such as vitamin E family compounds, acylcarnitines, and other metabolites to infer their role in resilience to coral diseases. As time-resolved multi-omics datasets are generated for disease-impacted corals, our approach and findings will be valuable in providing insight into the mechanisms of disease resistance.

Bacteria respond to changes in their external environment, such as temperature, by changing the transcription of their genes. We know little about how these regulatory patterns evolve. We used RNA-seq to study the transcriptional response to a shift from 37°C to 15°C in wild-type Escherichia coli, Salmonella enterica, Citrobacter rodentium, Enterobacter cloacae, Klebsiella pneumoniae, and Serratia marcescens, as well as ∆rpoS strains of E. coli and S. enterica. We found that these species change the transcription of between 626 and 1057 genes in response to the temperature shift, but there were only 16 differentially expressed genes in common among the six species. Species-specific transcriptional patterns of shared genes were a prominent cause of this lack of conservation. Gene ontology enrichment of regulated genes suggested many species-specific phenotypic responses to temperature changes, but enriched terms associated with iron metabolism, central metabolism, and biofilm formation were implicated in at least half of the species. The alternative sigma factor RpoS regulated about 200 genes between 37°C and 15°C in both E. coli and S. enterica, with only 83 genes in common between the two species. Overall, there was limited conservation of the response to low temperature generally, or the RpoS-regulated part of the response specifically. This study suggests that species-specific patterns of transcription of shared genes, rather than horizontal acquisition of unique genes, are the major reason for the lack of conservation of the transcriptomic response to low temperature.

Importance: We studied how different species of bacteria from the same Family (Enterobacteriaceae) change the expression of their genes in response to a decrease in temperature. Using de novo-generated parallel RNA-seq data sets, we found that the six species in this study change the level of expression of many of their genes in response to a shift from human body temperature (37°C) to a temperature that might be found out of doors (15°C). Surprisingly, there were very few genes that change expression in all six species. This was due in part to differences in gene content, and in part due to shared genes with distinct expression profiles between the species. This study is important to the field because it illustrates that closely related species can share many genes but not use those genes in the same way in response to the same environmental change.

Legionella pneumophila uses over 300 translocated effector proteins to rewire host cells during infection and create a replicative niche for intracellular growth. To date, several studies have identified L. pneumophila effectors that indirectly and directly regulate the activity of other effectors, providing an additional layer of regulatory complexity. Among these are "metaeffectors," a special class of effectors that regulate the activity of other effectors once inside the host. A defining feature of metaeffectors is direct, physical interaction with a target effector. Metaeffector identification, to date, has depended on phenotypes in heterologous systems and experimental serendipity. Using a multiplexed, recombinant barcode-based yeast two-hybrid technology we screened for protein-protein interactions among all L. pneumophila effectors and 28 components of the Dot/Icm type IV secretion system (>167,000 protein combinations). Of the 52 protein interactions identified by this approach, 44 are novel protein interactions, including 10 novel effector-effector interactions (doubling the number of known effector-effector interactions).

Importance: Secreted bacterial effector proteins are typically viewed as modulators of host activity, entering the host cytosol to physically interact with and modify the activity of one or more host proteins in support of infection. A growing body of evidence suggests that a subset of effectors primarily function to modify the activities of other effectors inside the host. These "effectors of effectors" or metaeffectors are often identified through experimental serendipity during the study of canonical effector function against the host. We previously performed the first global effector-wide genetic interaction screen for metaeffectors within the arsenal of Legionella pneumophila, an intracellular bacterial pathogen with over 300 effectors. Here, using a high-throughput, scalable methodology, we present the first global interaction network of physical interactions between L. pneumophila effectors. This data set serves as a complementary resource to identify and understand both the scope and nature of non-canonical effector activity within this important human pathogen.

The phylum Gemmatimonadota is widespread but rarely cultured and, in fact, there are only six described species isolated from soil, freshwater, and wastewater treatment. However, no isolates of Gemmatimonadota from marine environment have been described; thus, little is known about the physiology and metabolism of members of the marine lineages. In this study, four novel facultatively anaerobic bacterial strains belonging to Gemmatimonadota were isolated from marine sediments collected from Xiaoshi Island in Weihai, China, using an aerobic enrichment method. The integrated results of phylogenetic and phenotypic characteristics supported that these four strains represent one novel species in a novel genus, for which the name Gaopeijia maritima gen. nov., sp. nov. is proposed, as the first representative of novel taxa, Gaopeijiales ord. nov., Gaopeijiaceae fam. nov. in the class Longimicrobiia. Gaopeijiales was detected in 22,884 out of 95,549 amplicon data sets, mainly from soil. However, the highest mean relative abundances were in sponge (0.7%) and marine sediment (0.35%), showing salt-related character. Most of the Gaopeijiales subgroups potentially belong to the rare bacterial biosphere. The aerobic enrichment in this study could significantly increase the relative abundance of Gaopeijiales (from 0.37% to 2.6%). Furthermore, the metabolic capabilities inferred from high-quality representative Gaopeijiales genomes/MAGs suggest that this group primarily performs chemoorganoheterotrophic metabolism with facultatively anaerobic characteristics and possesses various secondary metabolite biosynthesis gene clusters (BGCs), mirroring those observed in the four novel strains.IMPORTANCEDespite rapid advances in molecular and sequencing technologies, obtaining pure cultures remains a crucial research goal in microbiology, as it is essential for a deeper understanding of microbial metabolism. Gemmatimonadota is a widespread but rarely cultured bacterial phylum. Currently, there are only six cultured strains of this interesting group, all isolated from non-marine environments. Little is known about the physiology and metabolism of members of the marine lineages. Here we isolated and characterized four novel marine strains, and proposed a new order Gaopeijiales within Gemmatimonadota. Furthermore, the global distribution, environmental preference, and metabolic potential of Gaopeijiales are analyzed using public data. Our work enriches the resources available for the under-represented phylum Gemmatimonadota and provides insights into the physiological and metabolic characteristics of the marine lineage (Gaopeijiales) through culturology and omics.

The widespread use of antimicrobials that target bacterial pathogens has driven evolution of resistance, compromising the efficacy of these bactericides. Understanding the emergence and spread of resistance genes via mobile genetic elements is crucial for combating antimicrobial resistance. Copper resistance (CuR) in Xanthomonas euvesicatoria pv. perforans has severely affected the efficacy of copper-based bactericides for controlling bacterial leaf spot disease of tomato and pepper. Here, we investigated the evolutionary pathways of CuR acquisition and dissemination in X. euvesicatoria pv. perforans using an extensive collection of strains. We determined that chromosomally encoded CuR predominates over plasmid-borne CuR in multiple distinct phylogenetic groups of X. euvesicatoria pv. perforans. Our analysis revealed a single site of chromosomal integration by a CuR genomic island, although the genomic island showed sequence variation among phylogenetic groups. While chromosomal CuR was more prevalent, strains with plasmid-borne resistance conferred greater copper tolerance. Additionally, we identified strains carrying two copies of CuR genes, on plasmid and chromosome, that exhibited increased copper tolerance. Strains of X. euvesicatoria pv. perforans from the USA shared identical CuR gene sequences whether on plasmids or chromosome while different alleles were found in strains from other countries. In contrast to X. euvesicatoria pv. perforans, plasmid-borne CuR predominated in closely related pathovar, X. euvesicatoria pv. euvesicatoria. Overall, these findings contribute to a better understanding of the evolution and persistence of CuR in X. euvesicatoria pv. perforans and its closest relatives.IMPORTANCEThe emergence of antimicrobial resistance is a significant threat to agricultural production as it reduces the efficacy of various antimicrobials including copper-based bactericides that are widely used to control plant diseases. The challenge of increasing antimicrobial resistance entering a production system necessitates a deeper understanding of the dynamics and mechanisms by which pathogens acquire resistance. As a result of this research, we have identified different mechanisms of copper resistance acquisition as well as levels of copper resistance in a devastating plant pathogen, X. euvesicatoria pv. perforans. The evolution and dissemination of copper resistance in strains through plasmid or chromosomally integrated genomic island or both presents barriers to current management approaches, where growers rely heavily on copper-based bactericides to manage disease outbreaks. This knowledge is crucial when considering the continued use of existing antimicrobials or adopting alternative antimicrobials in efforts to implement enhanced antimicrobial stewardship strategies in agriculture.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strains present a significant global public health threat due to their high mortality rates. This study investigated the genomic characteristics of seven ST11-K1 CR-hvKP isolates harboring highly homologous KPC-2-encoding multidrug-resistance plasmids. The strains were isolated from a Chinese tertiary hospital between 2017 and 2020. Whole-genome sequencing and bioinformatic analysis revealed various antibiotic resistance genes (ARGs) and virulence determinants. The bla_KPC-2-bearing plasmids that contain multiple antibiotic-resistance genes were also identified in these strains. ISfinder and Orifinder were applied to identify insertion sequences (IS) and conjugation-related factors among these bla_KPC-2-bearing plasmids. The bla_KPC-2 was highly consistent in seven bla_KPC-2-bearing plasmids (ISKpn6-bla_KPC-2-ISKpn27-ISYps3-IS26). In addition, we found a region composed of ISIR, Tn5393, and IS26. It was located upstream of the bla_CTX-M-15 gene and presented in six bla_KPC-2-bearing plasmids, with pCR-hvKP221-KPC-P3 as an exception. Conjugation experiments demonstrated the horizontal transfer of resistance plasmids pCR-hvKP128-KPC-P1 and pCR-hvKP132-KPC-P1 across species. Notably, pLVPK-like virulence plasmids carrying virulence gene clusters pCR-hvKP173-Vir-P1, and pCR-hvKP221-Vir-P1 were also detected. A fusional plasmid pCR-hvKP221-Vir-P2, which carries virulence gene clusters and ARGs, was also identified. Five CR-hvKP strains displayed enhanced biofilm formation and high virulence in vivo infection models. Phylogenetic and single nucleotide polymorphism (SNP) analyses indicated a close genetic relationship among the isolates, suggesting a subclade. These findings highlight the complex genetic profiles and potential transmission mechanisms of CR-hvKP strains.

Importance: We reported seven CR-hvKP strains all carried a highly homologous bla_KPC-2 integrated IncFⅡ-resistant plasmid, and two strains harbored virulence plasmids. Conjugation experiments confirmed the transferability of these plasmids, indicating a potential for resistance spread. Phylogenetic analysis clarified the relationship among the CR-hvKP isolates. This study provides insights into the phenotypic and genomic characteristics of seven ST11-K1 CR-hvKP strains. The high prevalence and potential for local outbreaks emphasize the need for effective control measures.

Segregation and mixing shape the structure and functioning of aquatic microbial communities, but their respective roles are challenging to disentangle in field studies. We explored the hypothesis that functional differences and beta diversity among stochastically assembled communities would increase in the absence of dispersal. Contrariwise, we expected biotic selection during homogenizing dispersal to reduce beta and gamma diversity as well as functional variability. This was experimentally addressed by examining the compositional and functional changes of 20 freshwater bacterial assemblages maintained at identical conditions over seven growth cycles for 34 days and subjected to two consecutive dispersal regimes. Initial dispersal limitation generated high beta diversity and led to the repeated emergence of community types that were dominated by particular taxa. Compositional stability and evenness of the community types varied over successive growth cycles, reflecting differences in functional properties. Carbon use efficiency increased during cultivation, with some communities of unique composition outperforming the replicate community types. Homogenizing dispersal led to high compositional similarity and reduced gamma diversity. While a neutral and a competition-based (Elo-rating) model together largely explained community assembly, a pseudomonad disproportionally dominated across communities, possibly due to interaction-related genomic traits. In conclusion, microbial assemblages stochastically generated by dispersal limitation can be gradually "refined" into distinct community types by subsequent deterministic processes. Segregation of communities represented an insurance mechanism for highly productive but competitively weak microbial taxa that were excluded during community coalescence.

Importance: We experimentally assessed the compositional and functional responses of freshwater bacterial assemblages exposed to two consecutive dispersal-related events (dispersal limitation and homogenizing dispersal) under identical growth conditions. While segregation led to a decreased local diversity, high beta diversity sustained regional diversity and functional variability. In contrast, homogenizing dispersal reduced the species pool and functional variability of the metacommunity. Our findings highlight the role of dispersal in regulating both diversity and functional variability of aquatic microbial metacommunities, thereby providing crucial insight to predict changes in ecosystem functioning.