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840000.9975Transferring knowledge of bacterial protein interaction networks to predict pathogen targeted human genes and immune signaling pathways: a case study on M. tuberculosis. BACKGROUND: Bacterial invasive infection and host immune response is fundamental to the understanding of pathogen pathogenesis and the discovery of effective therapeutic drugs. However, there are very few experimental studies on the signaling cross-talks between bacteria and human host to date. METHODS: In this work, taking M. tuberculosis H37Rv (MTB) that is co-evolving with its human host as an example, we propose a general computational framework that exploits the known bacterial pathogen protein interaction networks in STRING database to predict pathogen-host protein interactions and their signaling cross-talks. In this framework, significant interlogs are derived from the known pathogen protein interaction networks to train a predictive l(2)-regularized logistic regression model. RESULTS: The computational results show that the proposed method achieves excellent performance of cross validation as well as low predicted positive rates on the less significant interlogs and non-interlogs, indicating a low risk of false discovery. We further conduct gene ontology (GO) and pathway enrichment analyses of the predicted pathogen-host protein interaction networks, which potentially provides insights into the machinery that M. tuberculosis H37Rv targets human genes and signaling pathways. In addition, we analyse the pathogen-host protein interactions related to drug resistance, inhibition of which potentially provides an alternative solution to M. tuberculosis H37Rv drug resistance. CONCLUSIONS: The proposed machine learning framework has been verified effective for predicting bacteria-host protein interactions via known bacterial protein interaction networks. For a vast majority of bacterial pathogens that lacks experimental studies of bacteria-host protein interactions, this framework is supposed to achieve a general-purpose applicability. The predicted protein interaction networks between M. tuberculosis H37Rv and Homo sapiens, provided in the Additional files, promise to gain applications in the two fields: (1) providing an alternative solution to drug resistance; (2) revealing the patterns that M. tuberculosis H37Rv genes target human immune signaling pathways.201829954330
866310.9974CPR bacteria and DPANN archaea play pivotal roles in response of microbial community to antibiotic stress in groundwater. The accumulation of antibiotics in the natural environment can disrupt microbial population dynamics. However, our understanding of how microbial communities adapt to the antibiotic stress in groundwater ecosystems remains limited. By recovering 2675 metagenome-assembled genomes (MAGs) from 66 groundwater samples, we explored the effect of antibiotics on bacterial, archaeal, and fungal communities, and revealed the pivotal microbes and their mechanisms in coping with antibiotic stress. The results indicated that antibiotics had the most significant influence on bacterial and archaeal communities, while the impact on the fungal community was minimal. Analysis of co-occurrence networks between antibiotics and microbes revealed the critical roles of Candidate Phyla Radiation (CPR) bacteria and DPANN archaea, two representative microbial groups in groundwater ecosystem, in coping with antibiotic resistance and enhancing network connectivity and complexity. Further genomic analysis demonstrated that CPR bacteria carried approximately 6 % of the identified antibiotic resistance genes (ARGs), indicating their potential to withstand antibiotics on their own. Meanwhile, the genomes of CPR bacteria and DPANN archaea were found to encode diverse biosynthetic gene clusters (BGCs) responsible for producing antimicrobial metabolites, which could not only assist CPR and DPANN organisms but also benefit the surrounding microbes in combating antibiotic stress. These findings underscore the significant impact of antibiotics on prokaryotic microbial communities in groundwater, and highlight the importance of CPR bacteria and DPANN archaea in enhancing the overall resilience and functionality of the microbial community in the face of antibiotic stress.202438246077
673720.9974Microbial-mediated conversion of soil organic carbon co-regulates the evolution of antibiotic resistance. The influence of organic carbon on the proliferation of antibiotic resistance genes (ARGs) in the soil has been widely documented. However, it is unclear how soil organic carbon (SOC) interacts with the evolution of antibiotic resistance in bacteria. Here, we examined the variations in ARGs abundance during SOC mineralization and explored the microbiological mechanisms and key metabolic pathways involved in their coevolution. The results showed that the SOC mineralization rate was closely correlated with ARGs abundance (p < 0.05). High organic carbon (OC) mineralization was conducive to the occurrence of multidrug resistance genes. For example, multidrug_transporter and mexB increased 2.26 and 7.83 times from the initial level. The competitor (stress) evolutionary strategy model revealed that higher OC inputs drive environmental microorganisms to evolve from stress tolerant to high resistance and strong adaptation. Meta-genomic and transcriptomic analyses revealed that the conversion process of pyruvate to acetyl-CoA to acetate was the critical metabolic pathway for the co-regulation of antibiotic resistance. Gene deletion validation trials have demonstrated that the key functional genes (ackA and pta) involved in this process can modulate the development of vancomycin and multidrug resistance. This outcome provides a preliminary framework for microbial mechanisms that target the co-regulation of microbial OC conversion and the evolution of antibiotic resistance.202438688217
881730.9973Study on the estradiol degradation gene expression and resistance mechanism of Rhodococcus R-001 under low-temperature stress. Estradiol (E2), an endocrine disruptor, acts by mimicking or interfering with the normal physiological functions of natural hormones within organisms, leading to issues such as endocrine system disruption. Notably, seasonal fluctuations in environmental temperature may influence the degradation speed of estradiol (E2) in the natural environment, intensifying its potential health and ecological risks. Therefore, this study aims to explore how bacteria can degrade E2 under low-temperature conditions, unveiling their resistance mechanisms, with the goal of developing new strategies to mitigate the threat of E2 to health and ecological safety. In this paper, we found that Rhodococcus equi DSSKP-R-001 (R-001) can efficiently degrade E2 at 30 °C and 10 °C. Six genes in R-001 were shown to be involved in E2 degradation by heterologous expression at 30 °C. Among them, 17β-HSD, KstD2, and KstD3, were also involved in E2 degradation at 10 °C; KstD was not previously known to degrade E2. RNA-seq was used to characterize differentially expressed genes (DEGs) to explore the stress response of R-001 to low-temperature environments to elucidate the strain's adaptation mechanism. At the low temperature, R-001 cells changed from a round spherical shape to a long rod or irregular shape with elevated unsaturated fatty acids and were consistent with the corresponding genetic changes. Many differentially expressed genes linked to the cold stress response were observed. R-001 was found to upregulate genes encoding cold shock proteins, fatty acid metabolism proteins, the ABC transport system, DNA damage repair, energy metabolism and transcriptional regulators. In this study, we demonstrated six E2 degradation genes in R-001 and found for the first time that E2 degradation genes have different expression characteristics at 30 °C and 10 °C. Linking R-001 to cold acclimation provides new insights and a mechanistic basis for the simultaneous degradation of E2 under cold stress in Rhodococcus adaptation.202438677604
354840.9973From flagellar assembly to DNA replication: CJSe's role in mitigating microbial antibiotic resistance genes. The emergence of Antibiotic Resistance Genes (ARGs) in Campylobacter jejuni (CJ) poses a severe threat to food safety and human health. However, the specific impact of CJ and its variants on ARGs and other related factors remains to be further elucidated. Herein, integrated metagenomic sequencing and co-occurrence network analysis approach were employed to investigate the impact of CJ and CJ incorporated with biogenic selenium (CJSe) on ARGs, flagellar assembly pathways, microbial communities, and DNA replication pathways in chicken manure. Compared to the Control (CON) and CJ groups, the CJSe group exhibited 2.4-fold increase selenium levels (P < 0.01) in chicken manure. Notable differences were also observed between the CJ and CJSe groups, with sequence results showing a CJ > CJSe > CON trend in total ARG copy numbers. Furthermore, the CJSe group showed 31.6 % fewer flagellar assembly genes compared to the CJ group. Additionally, compared to the CJ group, CJSe inhibited pathways such as basal body/hook (e.g., FliH, FliO, FliQ reduced by 25-52 %) and stator (MotB downregulated by 42.3 %), suppressing flagellar assembly. We also found that both CJ and CJSe influenced bacterial DNA replication pathways, with the former increasing ARG-carrying bacteria and the latter, under selenium-induced selective pressure, reducing ARG-carrying bacteria. Moreover, compared to the CJ group, the CJSe group showed a significantly lower 9.72 % copy number of total archaeal DNA replication genes. Furthermore, through intricate co-occurrence network analysis, we discovered the complex interplay between changes in ARGs and bacterial and archaeal DNA replication dynamics within the microbial community. These findings indicate that CJSe mitigates the threat posed by CJ and reduces ARG prevalence, while its dual functionality enables applications in biofortified crop production and soil remediation in selenium-deficient regions, thereby advancing circular economy systems. While the current study demonstrates CJSe's dual functionality under controlled conditions, future work will implement a dedicated ecological risk assessment framework encompassing Se speciation/leaching tests and non-target organism assays to confirm environmental safety under field-relevant scenarios. This approach aligns with sustainable strategies for food security and public health safeguarding.202541108960
672650.9973A symbiotic gut bacterium enhances Aedes albopictus resistance to insecticide. BACKGROUND: The increasing insecticide resistance of Aedes albopictus puts many countries in Asia and Africa, including China, at great risk of a mosquito-borne virus epidemic. To date, a growing number of researches have focused on the relationship between intestinal symbiotic bacteria and their hosts' resistance to insecticides. This provides a novel aspect to the study of resistant mechanisms. METHODS/FINDINGS: This study reveals significant composition and dynamic changes in the intestinal symbiotic bacteria of Ae. albopictus between the resistant and susceptible strains based on full-length sequencing technology. The relative abundance of Serratia oryzae was significantly higher in the resistance strain than in the susceptible strains; also, the relative abundance of S. oryzae was significantly higher in deltamethrin-induced Ae. albopictus than in their counterpart. These suggested that S. oryzae may be involved in the development of insecticide resistance in Ae. albopictus. To explore the insecticide resistance mechanism, adult mosquitoes were fed with GFP-tagged S. oryzae, which resulted in stable bacterial enrichment in the mosquito gut without affecting the normal physiology, longevity, oviposition, and hatching rates of the host. The resistance measurements were made based on bioassays as per the WHO guidelines. The results showed that the survival rate of S. oryzae-enriched Ae. albopictus was significantly higher than the untreated mosquitoes, indicating the enhanced resistance of S. oryzae-enriched Ae. albopictus. Also, the activities of three metabolic detoxification enzymes in S. oryzae-enriched mosquitoes were increased to varying degrees. Meanwhile, the activity of extracellular enzymes released by S. oryzae was measured, but only carboxylesterase activity was detected. HPLC and UHPLC were respectively used to measure deltamethrin residue concentration and metabolite qualitative analysis, showing that the deltamethrin degradation efficiency of S. oryzae was positively correlated with time and bacterial amount. Deltamethrin was broken down into 1-Oleoyl-2-hydroxy-sn-glycero-3-PE and 2',2'-Dibromo-2'-deoxyguanosine. Transcriptome analysis revealed that 9 cytochrome P450s, 8 GSTs and 7 CarEs genes were significantly upregulated. CONCLUSIONS: S. oryzae can be accumulated into adult Ae. albopictus by artificial feeding, which enhances deltamethrin resistance by inducing the metabolic detoxification genes and autocrine metabolic enzymes. S. oryzae is vertically transmitted in Ae. albopictus population. Importantly, S. oryzae can degrade deltamethrin in vitro, and use deltamethrin as the sole carbon source for their growths. Therefore, in the future, S. oryzae may also be commercially used to break down the residual insecticides in the farmland and lakes to protect the environment.202235245311
866460.9973Genome-centric metagenomics reveals the host-driven dynamics and ecological role of CPR bacteria in an activated sludge system. BACKGROUND: Candidate phyla radiation (CPR) constitutes highly diverse bacteria with small cell sizes and are likely obligate intracellular symbionts. Given their distribution and complex associations with bacterial hosts, genetic and biological features of CPR bacteria in low-nutrient environments have received increasing attention. However, CPR bacteria in wastewater treatment systems remain poorly understood. We utilized genome-centric metagenomics to answer how CPR communities shift over 11 years and what kind of ecological roles they act in an activated sludge system. RESULTS: We found that approximately 9% (135) of the 1,526 non-redundant bacterial and archaeal metagenome-assembled genomes were affiliated with CPR. CPR bacteria were consistently abundant with a relative abundance of up to 7.5% in the studied activated sludge system. The observed striking fluctuations in CPR community compositions and the limited metabolic and biosynthetic capabilities in CPR bacteria collectively revealed the nature that CPR dynamics may be directly determined by the available hosts. Similarity-based network analysis further confirmed the broad bacterial hosts of CPR lineages. The proteome contents of activated sludge-associated CPR had a higher similarity to those of environmental-associated CPR than to those of human-associated ones. Comparative genomic analysis observed significant enrichment of genes for oxygen stress resistance in activated sludge-associated CPR bacteria. Furthermore, genes for carbon cycling and horizontal gene transfer were extensively identified in activated sludge-associated CPR genomes. CONCLUSIONS: These findings highlight the presence of specific host interactions among CPR lineages in activated sludge systems. Despite the lack of key metabolic pathways, these small, yet abundant bacteria may have significant involvements in biogeochemical cycling and bacterial evolution in activated sludge systems. Video Abstract.202336945052
471270.9973The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids. BACKGROUND: Sub-therapeutic antibiotics are widely used as growth promoters in the poultry industry; however, the resulting antibiotic resistance threatens public health. A plant-derived growth promoter, Macleaya cordata extract (MCE), with effective ingredients of benzylisoquinoline alkaloids, is a potential alternative to antibiotic growth promoters. Altered intestinal microbiota play important roles in growth promotion, but the underlying mechanism remains unknown. RESULTS: We generated 1.64 terabases of metagenomic data from 495 chicken intestinal digesta samples and constructed a comprehensive chicken gut microbial gene catalog (9.04 million genes), which is also the first gene catalog of an animal's gut microbiome that covers all intestinal compartments. Then, we identified the distinctive characteristics and temporal changes in the foregut and hindgut microbiota. Next, we assessed the impact of MCE on chickens and gut microbiota. Chickens fed with MCE had improved growth performance, and major microbial changes were confined to the foregut, with the predominant role of Lactobacillus being enhanced, and the amino acids, vitamins, and secondary bile acids biosynthesis pathways being upregulated, but lacked the accumulation of antibiotic-resistance genes. In comparison, treatment with chlortetracycline similarly enriched some biosynthesis pathways of nutrients in the foregut microbiota, but elicited an increase in antibiotic-producing bacteria and antibiotic-resistance genes. CONCLUSION: The reference gene catalog of the chicken gut microbiome is an important supplement to animal gut metagenomes. Metagenomic analysis provides insights into the growth-promoting mechanism of MCE, and underscored the importance of utilizing safe and effective growth promoters.201830482240
471080.9973Gene Co-Expression Network Analysis Reveals the Hub Genes and Key Pathways Associated with Resistance to Salmonella Enteritidis Colonization in Chicken. Salmonella negatively impacts the poultry industry and threatens animals' and humans' health. The gastrointestinal microbiota and its metabolites can modulate the host's physiology and immune system. Recent research demonstrated the role of commensal bacteria and short-chain fatty acids (SCFAs) in developing resistance to Salmonella infection and colonization. However, the complex interactions among chicken, Salmonella, host-microbiome, and microbial metabolites remain unelucidated. Therefore, this study aimed to explore these complex interactions by identifying the driver and hub genes highly correlated with factors that confer resistance to Salmonella. Differential gene expression (DEGs) and dynamic developmental genes (DDGs) analyses and weighted gene co-expression network analysis (WGCNA) were performed using transcriptome data from the cecum of Salmonella Enteritidis-infected chicken at 7 and 21 days after infection. Furthermore, we identified the driver and hub genes associated with important traits such as the heterophil/lymphocyte (H/L) ratio, body weight post-infection, bacterial load, propionate and valerate cecal contents, and Firmicutes, Bacteroidetes, and Proteobacteria cecal relative abundance. Among the multiple genes detected in this study, EXFABP, S100A9/12, CEMIP, FKBP5, MAVS, FAM168B, HESX1, EMC6, and others were found as potential candidate gene and transcript (co-) factors for resistance to Salmonella infection. In addition, we found that the PPAR and oxidative phosphorylation (OXPHOS) metabolic pathways were also involved in the host's immune response/defense against Salmonella colonization at the earlier and later stage post-infection, respectively. This study provides a valuable resource of transcriptome profiles from chicken cecum at the earlier and later stage post-infection and mechanistic understanding of the complex interactions among chicken, Salmonella, host-microbiome, and associated metabolites.202336902251
771390.9973Metagenome analyses of corroded concrete wastewater pipe biofilms reveal a complex microbial system. BACKGROUND: Concrete corrosion of wastewater collection systems is a significant cause of deterioration and premature collapse. Failure to adequately address the deteriorating infrastructure networks threatens our environment, public health, and safety. Analysis of whole-metagenome pyrosequencing data and 16S rRNA gene clone libraries was used to determine microbial composition and functional genes associated with biomass harvested from crown (top) and invert (bottom) sections of a corroded wastewater pipe. RESULTS: Taxonomic and functional analysis demonstrated that approximately 90% of the total diversity was associated with the phyla Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. The top (TP) and bottom pipe (BP) communities were different in composition, with some of the differences attributed to the abundance of sulfide-oxidizing and sulfate-reducing bacteria. Additionally, human fecal bacteria were more abundant in the BP communities. Among the functional categories, proteins involved in sulfur and nitrogen metabolism showed the most significant differences between biofilms. There was also an enrichment of genes associated with heavy metal resistance, virulence (protein secretion systems) and stress response in the TP biofilm, while a higher number of genes related to motility and chemotaxis were identified in the BP biofilm. Both biofilms contain a high number of genes associated with resistance to antibiotics and toxic compounds subsystems. CONCLUSIONS: The function potential of wastewater biofilms was highly diverse with level of COG diversity similar to that described for soil. On the basis of the metagenomic data, some factors that may contribute to niche differentiation were pH, aerobic conditions and availability of substrate, such as nitrogen and sulfur. The results from this study will help us better understand the genetic network and functional capability of microbial members of wastewater concrete biofilms.201222727216
9729100.9972Omics technology draws a comprehensive heavy metal resistance strategy in bacteria. The rapid industrial revolution significantly increased heavy metal pollution, becoming a major global environmental concern. This pollution is considered as one of the most harmful and toxic threats to all environmental components (air, soil, water, animals, and plants until reaching to human). Therefore, scientists try to find a promising and eco-friendly technique to solve this problem i.e., bacterial bioremediation. Various heavy metal resistance mechanisms were reported. Omics technologies can significantly improve our understanding of heavy metal resistant bacteria and their communities. They are a potent tool for investigating the adaptation processes of microbes in severe conditions. These omics methods provide unique benefits for investigating metabolic alterations, microbial diversity, and mechanisms of resistance of individual strains or communities to harsh conditions. Starting with genome sequencing which provides us with complete and comprehensive insight into the resistance mechanism of heavy metal resistant bacteria. Moreover, genome sequencing facilitates the opportunities to identify specific metal resistance genes, operons, and regulatory elements in the genomes of individual bacteria, understand the genetic mechanisms and variations responsible for heavy metal resistance within and between bacterial species in addition to the transcriptome, proteome that obtain the real expressed genes. Moreover, at the community level, metagenome, meta transcriptome and meta proteome participate in understanding the microbial interactive network potentially novel metabolic pathways, enzymes and gene species can all be found using these methods. This review presents the state of the art and anticipated developments in the use of omics technologies in the investigation of microbes used for heavy metal bioremediation.202438709343
8561110.9972Three-dimensional synergistic mechanism ofphysical injury, microbiota dysbiosis, and gene transfer in the gut of Cipangopaludina cathayensisunder microplastics and roxithromycin exposure. Microplastics (MPs) and antibiotics pose a combined threat to aquatic organisms by impairing gut health and promoting the spread of antibiotic resistance genes (ARGs). In this study, Cipangopaludina cathayensis was exposed for 28 days to polystyrene MPs, roxithromycin (ROX), and their combination to assess impacts on intestinal barrier integrity, microbiota composition, and ARG proliferation. MPs alone caused significant mucosal damage, villus atrophy, epithelial shedding, and reduced digestive enzyme activities. ROX exposure altered microbiota structure by increasing Bacteroidetes and reducing Firmicutes. Co-exposure (CM group) exacerbated epithelial injury and enzyme inhibition but partially restored balance through enrichment of SCFA-producing, anti-inflammatory bacteria. ARG levels in the CM group rose by over 1000 %, with notable increases in multidrug resistance genes (e.g., blaOXA10) and integrons (e.g., cIntI-1), mainly linked to Bacteroides and Proteobacteria. Transcriptomic data indicated oxidative stress and epithelial disruption under MPs, and upregulation of efflux and integron genes with ROX. Combined exposure triggered DNA repair and SOS pathways, facilitating horizontal gene transfer. These findings highlight a three-dimensional synergistic mechanism-physical damage, microbial dysbiosis, and gene transfer-that amplifies ARG dissemination and intestinal toxicity, underscoring the need to assess ecological risks of composite pollutants in freshwater systems.These processes form a self-reinforcing loop in which physical epithelial damage promotes microbial dysbiosis, which in turn facilitates ARG proliferation through increased permeability and immune disruption.202541067103
8666120.9972Decoding the genetic drivers of marine bacterial blooms through comparative genomics. BACKGROUND: While oligotrophic bacteria are known to dominate most marine microbial habitats, under certain conditions, such as during phytoplankton blooms, copiotrophs can dramatically increase in abundance and reach towering proportions of the bacterial communities. We are uncertain whether the bacteria exhibiting this capacity, which we denote as "bloomers," have specific functional characteristics or if, instead, they are randomly selected from the broader pool of copiotrophs. To explore the genomic determinants of this ecological trait, we conducted a comparative genomic analysis of bacterial genomes from microcosm experiments where grazer and viral presence was reduced and nutrient availability was increased, conditions that triggered bacterial blooms. RESULTS: We tested which functional genes were overrepresented in the bacteria that responded to the treatments, examining a total of 305 genomes from isolates and metagenome-assembled genomes (MAGs) that were categorized as copiotrophs or oligotrophs according to their codon usage bias (CUB). The responsive bacteria were enriched in genes related to transcriptional regulation in response to stimuli (mostly via two-component systems), transport, secretion, cell protection, catabolism of sugars and amino acids, and membrane/cell wall biosynthesis. These genes confer on them capabilities for adhesion, biofilm formation, resistance to stress, quorum sensing, chemotaxis, nutrient uptake, and fast replication. They were overrepresented mainly in copiotrophic genomes from the families Alteromonadaceae, Vibrionaceae, Rhodobacteraceae, Sphingomonadaceae, and Flavobacteriaceae. Additionally, we found that these responsive bacteria, when abundant, could affect biogeochemical cycling, particularly the phosphorus cycle. CONCLUSIONS: In this study, we provide insights into the functional characteristics that enable certain bacteria to rapidly respond to changes in the environment and bloom. We also hint at the ecological meaning and implications of these phenomena that could affect biogeochemical cycles in the oceans. Video Abstract.202541029845
8819130.9972Responses of Bacillus sp. under Cu(II) stress in relation to extracellular polymeric substances and functional gene expression level. The production and composition of extracellular polymeric substances (EPS), as well as the EPS-related functional resistance genes and metabolic levels of Bacillus sp. under Cu(II) stress, were investigated. EPS production increased by 2.73 ± 0.29 times compared to the control when the strain was treated with 30 mg L(-1) Cu(II). Specifically, the polysaccharide (PS) content in EPS increased by 2.26 ± 0.28 g CDW(-1) and the PN/PS (protein/polysaccharide) ratio value increased by 3.18 ± 0.33 times under 30 mg L(-1) Cu(II) compared to the control. The increased EPS secretion and higher PN/PS ratio in EPS strengthened the cells' ability to resist the toxic effect of Cu(II). Differential expression of functional genes under Cu(II) stress was revealed by Gene Ontology pathway enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The enriched genes were most obviously upregulated in the UMP biosynthesis pathway, the pyrimidine metabolism pathway, and the TCS metabolism pathway. This indicates an enhancement of EPS regulation-related metabolic levels and their role as a defense mechanism for cells to adapt to Cu(II) stress. Additionally, seven copper resistance genes were upregulated while three were downregulated. The upregulated genes were related to the heavy metal resistance, while downregulated genes were related to cell differentiation, indicating that the strain had initiated an obvious resistance to Cu(II) despite its severe cell toxicity. These results provided a basis for promoting EPS-regulated associated functional genes and the application of gene-regulated bacteria in heavy metal-containing wastewater treatment.202337195605
169140.9972Heavy metal resistance in Cupriavidus metallidurans CH34 is governed by an intricate transcriptional network. The soil bacterium Cupriavidus metallidurans CH34 contains a high number of heavy metal resistance genes making it an interesting model organism to study microbial responses to heavy metals. In this study the transcriptional response of strain CH34 was measured when challenged to sub-lethal concentrations of various essential or toxic metals. Based on the global transcriptional responses for each challenge and the overlap in upregulated genes between different metal responses, the sixteen metals were clustered in three groups. In addition, the transcriptional response of already known metal resistance genes was assessed, and new metal response gene clusters were identified. The majority of the studied metal response loci showed similar expression profiles when cells were exposed to different metals, suggesting complex interplay at transcriptional level between the different metal responses. The pronounced redundancy of these metal resistant regions-as illustrated by the large number of paralogous genes-combined with the phylogenetic distribution of these metal response regions within either evolutionary related or other metal resistant bacteria, provides important insights on the recent evolutionary forces shaping this naturally soil-dwelling bacterium into a highly metal-resistant strain well adapted to harsh and anthropogenic environments.201121706166
6740150.9972Metatranscriptomics reveals that plant tannins regulate the expression of intestinal antibiotic resistance genes in Qinghai voles (Neodon fuscus). Antibiotic resistance genes (ARGs) are a persistent harmful environmental pollutant, epidemic of ARGs thought to be a result of antibiotic misuse. Tannin acid (TA) is a natural plant compounds with bactericidal properties. Nowadays, TA is considered to be a potential replacement of antibiotics. However, the role of TA on ARGs is also not yet clear. To address this knowledge gap, we fed the model plateau animal Qinghai voles (Neodon fuscus) with different concentrations of TA. We used 16S rDNA sequencing for revealing total bacteria, 16S rRNA sequencing for revealing active bacteria, and metatranscriptomics (active function) sequencing for revealing ARGs and other functions. Our results showed that although TA reduced macrolide ARGs, TA group enriched 6-fold for tetracycline ARGs, 3-fold for multidrug ARGs, and 5-fold for aminoglycoside ARGs compared with control group. Moreover, TA reduced animal growth performance, and regulated gut microbiome more stable by improving microbial diversity. And TA promoted the production of short-chain fatty acids by gut microbes, such as lactate and acetate. This study reveals modulation of ARGs and gut microbiome by TA and also provides scientific value for the proper use of TA in feed and medical treatment.202539952456
5098160.9972Feature selection and aggregation for antibiotic resistance GWAS in Mycobacterium tuberculosis: a comparative study. INTRODUCTION: Drug resistance (DR) of pathogens remains a global healthcare concern. In contrast to other bacteria, acquiring mutations in the core genome is the main mechanism of drug resistance for Mycobacterium tuberculosis (MTB). For some antibiotics, the resistance of a particular isolate can be reliably predicted by identifying specific mutations, while for other antibiotics the knowledge of resistance mechanisms is limited. Statistical machine learning (ML) methods are used to infer new genes implicated in drug resistance leveraging large collections of isolates with known whole-genome sequences and phenotypic states for different drugs. However, high correlations between the phenotypic states for commonly used drugs complicate the inference of true associations of mutations with drug phenotypes by ML approaches. METHODS: Recently, several new methods have been developed to select a small subset of reliable predictors of the dependent variable, which may help reduce the number of spurious associations identified. In this study, we evaluated several such methods, namely, logistic regression with different regularization penalty functions, a recently introduced algorithm for solving the best-subset selection problem (ABESS) and "Hungry, Hungry SNPos" (HHS) a heuristic algorithm specifically developed to identify resistance-associated genetic variants in the presence of resistance co-occurrence. We assessed their ability to select known causal mutations for resistance to a specific drug while avoiding the selection of mutations in genes associated with resistance to other drugs, thus we compared selected ML models for their applicability for MTB genome wide association studies. RESULTS AND DISCUSSION: In our analysis, ABESS significantly outperformed the other methods, selecting more relevant sets of mutations. Additionally, we demonstrated that aggregating rare mutations within protein-coding genes into markers indicative of changes in PFAM domains improved prediction quality, and these markers were predominantly selected by ABESS, suggesting their high informativeness. However, ABESS yielded lower prediction accuracy compared to logistic regression methods with regularization.202540606161
8871170.9971Phage selection drives resistance-virulence trade-offs in Ralstonia solanacearum plant-pathogenic bacterium irrespective of the growth temperature. While temperature has been shown to affect the survival and growth of bacteria and their phage parasites, it is unclear if trade-offs between phage resistance and other bacterial traits depend on the temperature. Here, we experimentally compared the evolution of phage resistance-virulence trade-offs and underlying molecular mechanisms in phytopathogenic Ralstonia solanacearum bacterium at 25 °C and 35 °C temperature environments. We found that while phages reduced R. solanacearum densities relatively more at 25 °C, no difference in the final level of phage resistance was observed between temperature treatments. Instead, small colony variants (SCVs) with increased growth rate and mutations in the quorum-sensing (QS) signaling receptor gene, phcS, evolved in both temperature treatments. Interestingly, SCVs were also phage-resistant and reached higher frequencies in the presence of phages. Evolving phage resistance was costly, resulting in reduced carrying capacity, biofilm formation, and virulence in planta, possibly due to loss of QS-mediated expression of key virulence genes. We also observed mucoid phage-resistant colonies that showed loss of virulence and reduced twitching motility likely due to parallel mutations in prepilin peptidase gene, pilD. Moreover, phage-resistant SCVs from 35 °C-phage treatment had parallel mutations in type II secretion system (T2SS) genes (gspE and gspF). Adsorption assays confirmed the role of pilD as a phage receptor, while no loss of adsorption was found with phcS or T2SS mutants, indicative of other downstream phage resistance mechanisms. Additional transcriptomic analysis revealed upregulation of CBASS and type I restriction-modification phage defense systems in response to phage exposure, which coincided with reduced expression of motility and virulence-associated genes, including pilD and type II and III secretion systems. Together, these results suggest that while phage resistance-virulence trade-offs are not affected by the growth temperature, they could be mediated through both pre- and postinfection phage resistance mechanisms.202438525025
8696180.9971Specific Enriched Acinetobacter in Camellia Weevil Gut Facilitate the Degradation of Tea Saponin: Inferred from Bacterial Genomic and Transcriptomic Analyses. Beneficial gut bacteria can enhance herbivorous arthropod adaptation to plant secondary compounds (PSMs), and specialist herbivores provide excellent examples of this. Tea saponin (TS) of Camellia oleifera is triterpenoids toxic to seed-feeding weevil pest, Curculio chinensis (CW). Previous studies disclosed that Acinetobacter, which was specific enriched in the CW's gut, was involved in helping CW evade TS toxicity of C. oleifera. However, it is still not clear whether Acinetobacter is associated with other anti-insect compounds, and the molecular mechanism of Acinetobacter degradation of TS has not been clarified. To address these questions, we explored the relationship between host plant toxin content and Acinetobacter of CW gut bacteria. Results demonstrated that TS content significantly affected the CW gut microbiome structure and enriched bacteria functional for TS degradation. We further isolated Acinetobacter strain and conducted its genome and transcriptome analyses for bacterial characterization and investigation on its role in TS degradation. Biological tests were carried out to verify the ability of the functional bacterium within CW larvae to detoxify TS. Our results showed that TS-degrading bacteria strain (Acinetobacter sp. AS23) genome contains 47 genes relating to triterpenoids degradation. The AS23 strain improved the survival rate of CW larvae, and the steroid degradation pathway could be the key one for AS23 to degrade TS. This study provides the direct evidence that gut bacteria mediate adaptation of herbivorous insects to phytochemical resistance. IMPORTANCE Microorganism is directly exposed to the plant toxin environment and play a crucial third party in herbivores gut. Although previous studies have proved the existence of gut bacteria that help CWs degrade TS, the specific core flora and its function have not been explored. In this study, we investigated the correlation between the larva gut microbiome and plant secondary metabolites. Acinetobacter genus was the target flora related to TS degradation. There were many terpenoids genes in Acinetobacter sp. AS23 genome. Results of transcriptome analysis and biological tests suggested that steroid degradation pathway be the key pathway of AS23 to degrade TS. This study not only provides direct evidence that gut microbes mediate the rapid adaptation of herbivorous insects to phytochemical resistance, but also provides a theoretical basis for further research on the molecular mechanism of intestinal bacteria cooperating with pests to adapt to plant toxins.202236413019
8409190.9971Comparative genomics reveals key adaptive mechanisms in pathogen host-niche specialization. INTRODUCTION: Understanding the key factors that enable bacterial pathogens to adapt to new hosts is crucial, as host-microbe interactions not only influence host health but also drive bacterial genome diversification, thereby enhancing pathogen survival in various ecological niches. METHODS: We conducted a comparative genomic analysis of 4,366 high-quality bacterial genomes isolated from various hosts and environments. Bioinformatics databases and machine learning approaches were used to identify genomic differences in functional categories, virulence factors, and antibiotic resistance genes across different ecological niches. RESULTS: Significant variability in bacterial adaptive strategies was observed. Human-associated bacteria, particularly from the phylum Pseudomonadota, exhibited higher detection rates of carbohydrate-active enzyme genes and virulence factors related to immune modulation and adhesion, indicating co-evolution with the human host. In contrast, bacteria from environmental sources, particularly those from the phyla Bacillota and Actinomycetota, showed greater enrichment in genes related to metabolism and transcriptional regulation, highlighting their high adaptability to diverse environments. Bacteria from clinical settings had higher detection rates of antibiotic resistance genes, particularly those related to fluoroquinolone resistance. Animal hosts were identified as important reservoirs of resistance genes. Key host-specific bacterial genes, such as hypB, were found to potentially play crucial roles in regulating metabolism and immune adaptation in human-associated bacteria. DISCUSSION: These findings highlight niche-specific genomic features and adaptive mechanisms of bacterial pathogens. This study provides valuable insights into the genetic basis of host-pathogen interactions and offers evidence to inform pathogen transmission control, infection management, and antibiotic stewardship.202540547794