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218 result(s) for "Li, Yue-zhong"
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Global microbial community biodiversity increases with antimicrobial toxin abundance of rare taxa
One of the central questions in microbial ecology is how to explain the high biodiversity of communities. A large number of rare taxa in the community have not been excluded by abundant taxa with competitive advantages, a contradiction known as the biodiversity paradox. Recently, increasing evidence has revealed the central importance of antimicrobial toxins as crucial weapons of antagonism in microbial survival. The powerful effects of antimicrobial toxins result in simple combinations of microorganisms failing to coexist under laboratory conditions, but it is unclear whether they also have a negative impact on the biodiversity of natural communities. Here, we revealed that microbial communities worldwide universally possess functional potential for antimicrobial toxin production. Counterintuitively, the biodiversity of global microbial communities increases, rather than decreases, as the abundance of antimicrobial toxins in rare taxa rises. Rare taxa may encode more antimicrobial toxins than abundant taxa, which is associated with the maintenance of the high biodiversity of microbial communities amid complex interactions. Our findings suggest that the antagonistic interaction caused by antimicrobial toxins may play a positive role in microbial community biodiversity at the global scale.
Rare taxa modulate the emergence of dominants in microbial communities
Microbial ecosystems are almost always dominated by only a few species, but their diversity resides in the rare biosphere. These rare members are usually considered passive passengers with little influence, yet our work reveals that they can collectively determine which species to become the most abundant taxon. We describe this process as a “nomination–voting” system: competitive traits nominate potential dominants, while rare taxa vote for the ultimate winner through their complex interactions. Recognizing this hidden but decisive role of rare microbes provides a new perspective on community assembly and underscores how subtle ecological interactions shape community outcomes. This assembly framework offers new opportunities for the prediction, manipulation, and stabilization of agriculture, health, and environmental microbiomes.
Global assembly of microbial communities
Different habitats harbor different microbial communities with elusive assembly mechanisms. This study comprehensively investigated the global assembly mechanisms of microbial communities and effects of community-internal influencing factors using the Earth Microbiome Project (EMP) data set. We found that deterministic and stochastic processes contribute approximately equally to global microbial community assembly, and, specifically, deterministic processes generally play a major role in free-living and plant-associated (but not plant corpus) environments, while stochastic processes are the major contributor in animal-associated environments. In contrast with the assembly of microorganisms, the assembly of functional genes, predicted from PICRUSt, is mainly attributed to deterministic processes in all microbial communities. The sink and source microbial communities are normally assembled using similar mechanisms, and the core microorganisms are specific to different environment types. On a global scale, deterministic processes are positively related to the community alpha diversity, microbial interaction degree and bacterial predatory-specific gene abundance. Our analysis provides a panoramic picture and regularities of global and environment-typical microbial community assemblies. With the development of sequencing technologies, the research topic of microbial ecology has evolved from the analysis of community composition to community assembly, including the relative contribution of deterministic and stochastic processes for the formation and maintenance of community diversity. Many studies have reported the microbial assembly mechanisms in various habitats, but the assembly regularities of global microbial communities remain unknown. In this study, we analyzed the EMP data set using a combined pipeline to explore the assembly mechanisms of global microbial communities, microbial sources to construct communities, core microbes in different environment types, and community-internal factors influencing assembly. The results provide a panoramic picture and rules of global and environment-typical microbial community assemblies, which enhances our understandings of the mechanisms globally controlling community diversity and species coexistence.
Discovery of recombinases enables genome mining of cryptic biosynthetic gene clusters in Burkholderiales species
Bacterial genomes encode numerous cryptic biosynthetic gene clusters (BGCs) that represent a largely untapped source of drugs or pesticides. Mining of the cryptic products is limited by the unavailability of streamlined genetic tools in native producers. Precise genome engineering using bacteriophage recombinases is particularly useful for genome mining. However, recombinases are usually host-specific. The genome-guided discovery of novel recombinases and their transient expression could boost cryptic BGC mining. Herein, we reported a genetic system employing Red recombinases from Burkholderiales strain DSM 7029 for efficient genome engineering in several Burkholderiales species that currently lack effective genetic tools. Using specialized recombinases-assisted in situ insertion of functional promoters, we successfully mined five cryptic nonribosomal peptide synthetase/polyketide synthase BGCs, two of which were silent. Two classes of lipopeptides, glidopeptins and rhizomides, were identified through extensive spectroscopic characterization. This recombinase expression strategy offers utility within other bacteria species, allowing bioprospecting for potentially scalable discovery of novel metabolites with attractive bioactivities.
Differential crosstalk between toxin-immunity protein homologs divides Myxococcus nonself siblings into close and distant social relatives
This study significantly contributes to our knowledge of kin selection and social behavior in bacteria. The interactions between four homologous toxin–immunity protein systems of Myxococcus xanthus were investigated, and evidence was obtained that these systems can distinguish between self and nonself cells within a species. Importantly, this study revealed that nonself lineages, which display varying degrees of genetic relatedness, can co-grow and collaborate in distinct patterns. This discovery implies that the differential crosstalk between homologous toxin–immunity proteins can mimic the degree of kinship; through this activity, bacteria can differentiate close and distant relatives. This novel insight into bacterial social dynamics and kin discrimination supports kin selection theory and enriches our knowledge on microbial interactions and evolutionary strategies. These findings have broad implications for microbial ecology, evolution, and the development of cooperation strategies.
Anthropogenic climate change may reduce global diazotroph diversity
Climate change impacts microbial community structure and function, thus altering biogeochemical cycles. Biological nitrogen fixation by diazotrophs is involved in maintaining the balance of the global nitrogen cycle, but the global biogeographic patterns of diazotrophs and their responses to climate change remain unclear. In this study, we use a dataset of 1352 potential diazotrophs by leveraging the co-occurrence of nitrogenase genes ( nifHDK ) and analyse the global distribution of potential diazotrophs derived from 137,672 samples. Using the random forest model, we construct a global map of diazotroph diversity, revealing spatial variations in diversity across large scales. Feature importance shows that precipitation and temperature may act as drivers of diazotroph diversity, as these factors explain 54.2% of the variation in the global distribution of diazotroph diversity. Using projections of future climate under different shared socioeconomic pathways, we show that overall diazotroph diversity could decline by 1.5%–3.3%, with this decline further exacerbated by development patterns that increase carbon emissions. Our findings highlight the importance of sustainable development in preserving diazotrophs. Diazotrophs are a key driver of Earth’s nitrogen cycle, and their global distribution is shaped by environmental factors. This study reveals correlations between diazotroph biogeography and climate variables and uses projections to show that anthropogenic climate change may reduce global diazotroph diversity by 2100.
Quantifying functional redundancy in polysaccharide-degrading prokaryotic communities
Background Functional redundancy (FR) is widely present, but there is no consensus on its formation process and influencing factors. Taxonomically distinct microorganisms possessing genes for the same function in a community lead to within-community FR, and distinct assemblies of microorganisms in different communities playing the same functional roles are termed between-community FR. We proposed two formulas to respectively quantify the degree of functional redundancy within and between communities and analyzed the FR degrees of carbohydrate degradation functions in global environment samples using the genetic information of glycoside hydrolases (GHs) encoded by prokaryotes. Results Our results revealed that GHs are each encoded by multiple taxonomically distinct prokaryotes within a community, and the enzyme-encoding prokaryotes are further distinct between almost any community pairs. The within- and between-FR degrees are primarily affected by the alpha and beta community diversities, respectively, and are also affected by environmental factors (e.g., pH, temperature, and salinity). The FR degree of the prokaryotic community is determined by deterministic factors. Conclusions We conclude that the functional redundancy of GHs is a stabilized community characteristic. This study helps to determine the FR formation process and influencing factors and provides new insights into the relationships between prokaryotic community biodiversity and ecosystem functions. 719y1TiY6Es74zhUbSPagv Video Abstract
Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials
Therapy-related side effects and severe antimicrobial resistance still remain an obstacle to Helicobacter pylori eradication. This meta-analysis aimed to investigate the efficacy of Lactobacillus-supplemented triple therapy on H. pylori eradication rates and therapy-related side effects in children. Five studies involving 484 pediatric patients were included in our analysis. The pooled relative risk (RR) for eradication rates in the Lactobacillus group versus the control group was 1.19 [95% confidence interval (CI) 1.07–1.33]. In subgroup analyses based on dose and duration of Lactobacillus supplementation, the pooled RRs for eradication rates were 1.36 (95% CI 1.15–1.60) in the high-dose group, 1.08 (95% CI 0.86–1.35) in the low-dose group, 1.24 (95% CI 1.06–1.46) in the long-term group, and 1.17 (95% CI 0.96–1.44) in the short-term group. With respect to side effects, Lactobacillus supplementation significantly reduced the incidence of diarrhea (RR = 0.30, 95% CI 0.10–0.85).Conclusions: Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children. And a higher dose and a longer duration of supplementation may conduce to the positive impact of Lactobacillus on H. pylori eradication.What is Known:• Probiotics-supplemented triple therapy may be beneficial in improving H. pylori eradication rates and reducing therapy-related side effects in children. However, not all probiotics are beneficial to H. pylori eradication and the pooled outcomes based on different probiotics may be erroneously extrapolated to other ineffective strains.What is New:• Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children.
Engineering the acyltransferase domain of epothilone polyketide synthase to alter the substrate specificity
Background Polyketide synthases (PKSs) include ketone synthase (KS), acyltransferase (AT) and acyl carrier protein (ACP) domains to catalyse the elongation of polyketide chains. Some PKSs also contain ketoreductase (KR), dehydratase (DH) and enoylreductase (ER) domains as modification domains. Insertion, deletion or substitution of the catalytic domains may lead to the production of novel polyketide derivatives or to the accumulation of desired products. Epothilones are 16-membered macrolides that have been used as anticancer drugs. The substrate promiscuity of the module 4 AT domain of the epothilone PKS (EPOAT4) results in production of epothilone mixtures; substitution of this domain may change the ratios of epothilones. In addition, there are two dormant domains in module 9 of the epothilone PKS. Removing these redundant domains to generate a simpler and more efficient assembly line is a desirable goal. Results The substitution of module 4 drastically diminished the activity of epothilone PKS. However, with careful design of the KS-AT linker and the post-AT linker, replacing EPOAT4 with EPOAT2, EPOAT6, EPOAT7 or EPOAT8 (specifically incorporating methylmalonyl-CoA (MMCoA)) significantly increased the ratio of epothilone D ( 4 ) to epothilone C ( 3 ) (the highest ratio of 4 : 3  = 4.6:1), whereas the ratio of 4 : 3 in the parental strain Schlegelella brevitalea 104-1 was 1.4:1. We also obtained three strains by swapping EPOAT4 with EPOAT3, EPOAT5, or EPOAT9, which specifically incorporate malonyl-CoA (MCoA). These strains produced only epothilone C, and the yield was increased by a factor of 1.8 compared to that of parental strain 104-1. Furthermore, mutations of five residues in the AT domain identified Ser310 as the critical factor for MMCoA recognition in EPOAT4. Then, the mutation of His308 to valine or tyrosine combined with the mutation of Phe310 to serine further altered the product ratios. At the same time, we successfully deleted the inactive module 9 DH and ER domains and fused the ΨKR domain with the KR domain through an ~ 25-residue linker to generate a productive and simplified epothilone PKS. Conclusions These results suggested that the substitution and deletion of catalytic domains effectively produces desirable compounds and that selection of the linkers between domains is crucial for maintaining intact PKS catalytic activity.
Identification of Prospective Ebola Virus VP35 and VP40 Protein Inhibitors from Myxobacterial Natural Products
The Ebola virus (EBOV) is a lethal pathogen causing hemorrhagic fever syndrome which remains a global health challenge. In the EBOV, two multifunctional proteins, VP35 and VP40, have significant roles in replication, virion assembly, and budding from the cell and have been identified as druggable targets. In this study, we employed in silico methods comprising molecular docking, molecular dynamic simulations, and pharmacological properties to identify prospective drugs for inhibiting VP35 and VP40 proteins from the myxobacterial bioactive natural product repertoire. Cystobactamid 934-2, Cystobactamid 919-1, and Cittilin A bound firmly to VP35. Meanwhile, 2-Hydroxysorangiadenosine, Enhypyrazinone B, and Sorangiadenosine showed strong binding to the matrix protein VP40. Molecular dynamic simulations revealed that, among these compounds, Cystobactamid 919-1 and 2-Hydroxysorangiadenosine had stable interactions with their respective targets. Similarly, molecular mechanics Poisson–Boltzmann surface area (MMPBSA) calculations indicated close-fitting receptor binding with VP35 or VP40. These two compounds also exhibited good pharmacological properties. In conclusion, we identified Cystobactamid 919-1 and 2-Hydroxysorangiadenosine as potential ligands for EBOV that target VP35 and VP40 proteins. These findings signify an essential step in vitro and in vivo to validate their potential for EBOV inhibition.