Transfer and accumulation of antibiotic resistance genes and bacterial pathogens in the mice gut due to consumption of organic foods.

Over the last few decades, organic food demand has grown largely because of increasing personal health concerns. Organic farming introduces antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) into foods. However, potential effects of organic foods on the gut microbiome and ARGs have been overlooked. Using high-throughput quantitative PCR and 16S rRNA high-throughput sequencing technology, we examined 132 ARGs from major classes, eight transposase genes, universal class I integron-integrase gene (intI), clinical class I integron-integrase gene (cintI), and the bacterial community in mouse gut after 8 weeks with an either organic or inorganic lettuce and wheat diet. A total of 8 types of major ARGs and 10 mobile genetic elements (MGEs) were detected in mice gut, including tetracycline, multidrug, sulfonamide, aminoglycoside, beta-lactamase, chloramphenicol, MLSB and vancomycin resistance genes. We found that abundance and diversity of ARGs, mobile gene elements, and potential ARB in the gut increased with time after consumption of organic foods, whereas no significant changes were observed in inorganic treated groups. Moreover, MGEs, including IS613, Tp614 and tnpA_03 were found to play an important role in regulating ARG profiles in the gut microbiome following consumption of organic foods. Importantly, feeding organic food increased the relative abundance of the potentially antibiotic-resistant pathogens, Bacteroides and Streptococcus. Our results confirm that there is an increasing risk of ARGs and ARB in the gut microbiome, which highlights the importance of organic food industries taking into account the potential accumulation and transmission of ARGs as a risk factor.

Phylogenetic distance affects the artificial microbial consortia's effectiveness and colonization during the bioremediation of polluted soil with Cr(VI) and atrazine.

Soils co-contaminated with heavy metals and organic pollutants are common and threaten the natural environment and human health. Although artificial microbial consortia have advantages over single strains, the mechanism affecting their effectiveness and colonization in polluted soils still requires determination. Here, we constructed two kinds of artificial microbial consortia from the same or different phylogenetic groups and inoculated them into soil co-contaminated with Cr(VI) and atrazine to study the effects of phylogenetic distance on consortia effectiveness and colonization. The residual concentrations of pollutants demonstrated that the artificial microbial consortium from different phylogenetic groups achieved the highest removal rates of Cr(VI) and atrazine. The removal rate of 400 mg/kg atrazine was 100%, while that of 40 mg/kg Cr(VI) was 57.7%. High-throughput sequence analysis showed that the soil bacterial negative correlations, core genera, and potential metabolic interactions differed among treatments. Furthermore, artificial microbial consortia from different phylogenetic groups had better colonization and a more significant effect on the abundance of native core bacteria than consortia from the same phylogenetic group. Our study highlights the importance of phylogenetic distance on consortium effectiveness and colonization and offers insight into the bioremediation of combined pollutants.

Geographic characteristics and environmental variables determine the diversities and assembly of the algal communities in interconnected river-lake system.

Algal blooms in lakes are a major hazard worldwide. Although various geographical and environmental patterns affect algal communities during river-lake transit, a thorough understanding of what patterns shape the algal communities is still rarely researched, particularly in complex interconnected river-lake systems. In this study, focusing on the most typical interconnected river-lake system in China, the Dongting Lake, we collected paired water and sediment samples in summer, when algal biomass and growth rate are at high levels. Based on 23S rRNA gene sequencing, we investigated the heterogeneity and the differences in assembly mechanisms of planktonic and benthic algae in Dongting Lake. Planktonic algae contained more Cyanobacteria and Cryptophyta, while sediment harbored higher proportions of Bacillariophyta and Chlorophyta. For planktonic algae, stochastic dispersal dominated the assembly of the communities. Upstream rivers and confluences were important sources of planktonic algae in lakes. Meanwhile, for benthic algae, deterministic environmental filtering shaped the communities, and the proportion of benthic algae exploded with increasing N:P ratio and Cu concentration until reaching thresholds of 1.5 and 0.013 g/kg respectively, and then started falling, showing non-linear responses. This study revealed the variability of different aspects of algal communities in different habitats, traced the main sources of planktonic algae, and identified the thresholds for benthic algal shifts in response to environmental filters. Hence, upstream and downstream monitoring as well as thresholds of environmental factors should be considered in further aquatic ecological monitoring or regulatory programs of harmful algal blooms in these complex systems.

The impact of pharmacist early active consultation (PEAC) on multidrug resistance organism treatment outcomes: A prospective historically controlled study.

Background and aim: Infectious disease (ID) consultation can improve multidrug-resistant organism (MDRO) treatment outcomes. However, the impact of clinical pharmacists' ID consultation on MDRO therapy, especially early initiation, has not been reported. In this study, we try to explore the impact of the pharmacist early active consultation (PEAC) on MDRO patient management. Methods: We conducted a prospective historical controlled study based on PEAC in MDRO patients. The retrospective control group was patients hospitalized 18 months before the PEAC initiation, and the prospective PEAC group was patients hospitalized 18 months after the PEAC initiation. Primary endpoint was 30-day all-cause mortality. Secondary outcomes were MDRO clinical outcome, duration of antibiotic use, length of stay, antibiotic consumption and antibiotic costs. Further subgroup analysis of secondary outcomes was performed by the condition at admission, MDRO pathogenicity and MDRO clinical outcome. Results: 188 MDRO patients were included. After adjusting for potential predictors, PEAC reduced the 30-day all-cause mortality by 70% (HR 0.30, 95% CI 0.09-0.96, p = 0.042). PEAC group had clinical improvement than control group (89.47% vs. 65.59%, p < 0.001), especially in patients with non-severe clinical conditions at admission (98.41% vs. 70.18%, p < 0.001). However, no significant differences were found between groups in length of stay, antibiotics consumption, and antibiotics costs. Conclusion: Early active pharmacy ID consultation can reduce 30-day all-cause mortality and improve clinical outcomes in MDRO patients.

Engineering artificial microbial consortia based on division of labor promoted simultaneous removal of Cr(VI)-atrazine combined pollution.

Combined pollution caused by organic pollutants and heavy metals is common in polluted sites and wastewater. Engineering artificial microbial consortia offers a promising approach to address this complex issue. However, the mutualistic interactions and the critical function of specific microbe within microbial consortia remain unclear. In this study, based on division of labor, we respectively co-cultured two Cr(VI)-reducing strains, Paenarthrobacter nitroguajacolicus C1 and Pseudomonas putida C2, with an atrazine-degrading strain, Paenarthrobacter ureafaciens AT. After 5 days, up to 95 % Cr(VI) and 100 % atrazine were removed from the cocultures. Strain AT degraded nearly all atrazine and contributed only to a fraction of Cr(VI) reduction, whereas C1 promoted 41 % Cr(VI) transformation to Cr(III) fixed in cells, and C2 promoted 91 % Cr(VI) transformation to soluble Cr(III). Metabolic analyses of the cocultures and monocultures demonstrated that AT provided C1 with isopropylamine by passive diffusion and C2 with other effective nitrogen resources by cell-cell surface contact to promote their growth. Soil experiments also showed that treatments with AT and C2 achieved the highest Cr(VI) reduction and no atrazine residue. Our results indicate that engineering artificial microbial consortia based on division of labor and metabolic interactions is effective in promoting highly efficient bioremediation of combined pollution.

Asparaginase-related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System (FAERS) data and literature review.

WHAT IS KNOWN AND OBJECTIVE: Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been elucidated. The purpose of this study was to determine the potential association between asparaginase and DKA and analyse related clinical characteristics and possible risk factor. METHODS: Disproportionality analysis with the reporting odd ratio (ROR) was used to detect the adverse reaction signals of asparaginase-associated DKA in Food and Drug Administration Adverse Event Reporting System (FAERS). A literature review was conducted to further analyse clinical characteristics, possible risk factor and something noteworthy in asparaginase-associated DKA. RESULTS AND DISCUSSION: A total of 12 reports of DKA associated with l-asparaginase (l-asp) and 6 reports associated with pegaspargase (PEG-asp) were extracted in FAERS, more than 50% of the cases were classified as serious adverse events. DKA was a positive signal of l-asp (ROR = 2.397, 95% CI 1.360-4.226), while not closely related to the use of PEG-asp (ROR = 1.602, 95% CI 0.719-3.570). Searched in PubMed, Embase and Web of Science, a total of eight patients were collected. The patients were mainly adolescent patients, aged between 11 and 25 years old with a median age of 16 years. Drug dosage form distribution is unbalanced, 7 patients received l-asp and only 1 received PEG-asp. WHAT IS NEW AND CONCLUSIONS: The ROR of KDA caused by l-asp was statistically significant, but there was not a statistical association for DKA caused by PEG-asp. Asparaginase dosage form may affect the occurrence of DKA, but further research is needed.

Measuring Well-Being of Migrant Gig Workers: Exampled as Hangzhou City in China.

The consistent innovations and applications of information technology drive the vigorous development of the gig economy, and generate gig workers such as food delivery workers and couriers, and make a great contribution to stabilizing employment and increasing income. Gig workers, mostly made up of migrants, and suffer from job and status difficulties. Research on the well-being of migrant gig workers can reveal the practical problems and provide suggestions for narrowing the wealth gap to promote social fairness and justice. Taking Hangzhou city in China as an example, this paper explores the well-being of food delivery workers, couriers, and online car-hailing drivers as representatives of migrant gig workers. Firstly, the relevant data are acquired through the questionnaire. Secondly, the characteristics of this group are analyzed through descriptive analysis, namely: most of them are migrant workers aged between 20 and 39 with low occupation satisfaction due to insufficient social security coverage and limited well-being, despite relatively high income. Based on the analysis of differences in demographic variables and structural equation modeling, the factors affecting the well-being of migrant gig workers are studied, which mainly are occupation satisfaction, social interaction, and social security. The results show that occupation satisfaction is positively affected by family characteristics, social interaction, and social security. In addition, family characteristics and social security positively impact social interaction, but the former has no significant effect on well-being. Finally, this paper enriches the research on the well-being of specific migrant gig workers and gives policy suggestions for enhancing the well-being of migrant gig workers in Hangzhou city from the perspective of optimizing the mechanism, pilot construction, and platform provision.

Pn-AqpC-Mediated Fermentation Pattern Coordination with the Two-Component System 07 Regulates Host N-Glycan Degradation of Streptococcus pneumoniae.

The opportunistic pathogen Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal commensal, and host N-glycan metabolism promotes its colonization and invasion. It has been reported that glucose represses, while fetuin, a glycoconjugated model protein, induces, the genes involved in N-glycan degradation through the two-component system TCS07. However, the mechanisms of glucose repression and TCS07 induction remain unknown. Previously, we found that the pneumococcal aquaglyceroporin Pn-AqpC facilitates oxygen uptake, thereby contributing to the antioxidant potential and virulence. In this study, through Tandem Mass Tag (TMT) quantitative proteomics, we found that the deletion of Pn-aqpC caused a marked upregulation of 11 proteins involved in N-glycan degradation in glucose-grown pneumococcus R6. Both quantitative RT-PCR and GFP fluorescence reporters revealed that the upregulation of N-glycan genes was completely dependent on response regulator (RR) 07, but not on the histidine kinase HK07 of TCS07 or the phosphoryl-receiving aspartate residue of RR07 in ΔPn-aqpC, indicating that RR07 was activated in an HK07-independent manner when Pn-AqpC was absent. The deletion of Pn-aqpC also enhanced the expression of pyruvate formate lyase and increased formate production, probably due to reduced cellular oxygen content, indicating that a shunt of glucose catabolism to mixed acid fermentation occurs. Notably, formate induced the N-glycan degradation genes in glucose-grown R6, but the deletion of rr07 abolished this induction, indicating that formate activates RR07. However, the induction of N-glycan degradation proteins reduced the intraspecies competition of R6 in glucose. Therefore, although N-glycan degradation promotes pneumococcal pathogenesis, the glucose metabolites-based RR07 regulation reported here is of importance for balancing growth fitness and the pathogenicity of pneumococcus. IMPORTANCE Pneumococcus, a human opportunistic pathogen, is capable of metabolizing host complex N-glycans. N-glycan degradation promotes pneumococcus colonization in the nasopharynx as well as invasion into deeper tissues, thus significantly contributing to pathogenesis. It is known that the two-component system 07 induces the N-glycan metabolizing genes; however, how TCS07 is activated remains unknown. This study reveals that formate, the anaerobic fermentation metabolite of pneumococcus, is a novel activator of the response regulator (RR) 07. Although the high expression of N-glycan degradation genes promotes pneumococcal colonization in the nasopharynx and pathogenesis, this reduces pneumococcal growth fitness in glucose as indicated in this work. Notably, the presence of Pn-AqpC, an oxygen-transporting aquaglyceroporin, enables pneumococcus to maintain glucose homolactic acid fermentation, thus reducing formate production, maintaining RR07 inactivation, and controlling N-glycan degrading genes at a non-induced status. Thus, this study highlights a novel fermentation metabolism pattern linking TCS-regulated carbohydrate utilization strategies as a trade-off between the fitness and the pathogenicity of pneumococcus.

Comparison of the efficiency and microbial mechanisms of chemical- and bio-surfactants in remediation of petroleum hydrocarbon.

Surfactant-enhanced remediation (SER) is one of the most effective methods for petroleum hydrocarbon-contaminated sites compared to single physical and chemical methods. However, biosurfactants are not as commonly used as chemical surfactants, and the actual remediation effects and related mechanisms remain undefined. Therefore, to comprehensively compare the remediation effects and biological mechanisms of biosurfactants and chemical surfactants, soil column leaching experiments including two biosurfactants (rhamnolipids and lipopeptide) and three commercially used chemical surfactants (Tween 80, Triton X-100, and Berol 226SA) were conducted. After seven days of leaching, rhamnolipids exhibited the highest petroleum hydrocarbon removal rate of 61.01%, which was superior to that of chemical surfactants (11.73-18.75%) in n-alkanes C10-C30. Meanwhile, rhamnolipids exhibited a great degradation advantage of n-alkanes C13-C28, which was 1.22-30.55 times that of chemical surfactants. Compared to chemical surfactants, biosurfactants significantly upregulated the soil's biological functions, including soil conductivity (80.90-155.56%), and soil enzyme activities of lipase (90.31-497.10%), dehydrogenase (325.00-655.56%), core enzyme activities of petroleum hydrocarbon degradation, and quorum sensing between species. Biosurfactants significantly changed the composition of Pseudomonas, Citrobacter, Acidobacteriota, and Enterobacter at the genus level. Meanwhile, chemical surfactants had less influence on the bacterial community and interactions between species. Moreover, the biosurfactants enhanced the microbial interactions and centrality of petroleum hydrocarbon degraders in the community based on the network. Overall, this work provides a systematic comparison and understanding of the chemical- and bio-surfactants used in bioremediation. In the future, we intend to apply biosurfactants to practical petroleum hydrocarbon-contaminated fields to observe realistic remediation effects and compare their functional mechanisms.

Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.

Differences in pharmacokinetics/pharmacodynamics (PK/PD) target attainment are rarely considered when antifungals are switched in critically ill patients. This study intends to explore whether the antifungal de-escalation treatment strategy and the new intermittent dosing strategy of echinocandins in critically ill patients are able to achieve the corresponding PK/PD targets. The published population PK models of antifungals in critically ill patients and a public data set from the MIMIC-III database (n = 662) were employed to evaluate PK/PD target attainment of different dosing regimens of antifungals. Cumulative fraction of response (CFR) was calculated for each dosing regimen. Most guideline-recommended dosing regimens of fluconazole and voriconazole could achieve target exposure as de-escalation treatment in critically ill patients. For initial echinocandin treatment, achievement of the target exposure decreased as body weight increased, and the intermittent dosing strategy had a slightly higher CFR value in most simulations compared to conventional dosing strategy. For Candida albicans and Candida glabrata infection, caspofungin at the lowest dose achieved a CFR of >90%, while micafungin or anidulafungin required almost the highest doses simulated in this study to achieve the same effect. None of the echinocandins other than 150 mg every 24 h (q24h) or 200 mg q48h of caspofungin achieved the target CFR for Candida parapsilosis infection. These findings support the guideline-recommended dose of triazoles for antifungal de-escalation treatment and confirm the insufficient dosage of echinocandins in critically ill patients, indicating that a dosing regimen based on body weight or intermittent dosing of echinocandins may be required.

Optimization of conditions for a surfactant-producing strain and application to petroleum hydrocarbon-contaminated soil bioremediation.

Petroleum hydrocarbon-contaminated sites have been mainly remediated through the surfactant-enhanced soil leaching method. However, the commonly used chemical surfactants have poor biocompatibility and are prone to form residues in fields. Therefore, the purpose of this research is to establish an effective system of biosurfactant remediation in the field and provide instructions for common bioremediation challenges. First, wild-type Bacillus amyloliquefaciens A3, which produced lipopeptide biosurfactant, was used to improve the production of biosurfactant by atmosphere and room temperature plasma (ARTP) mutagenesis. Second, the mutant 1-24 was selected from a total of 174 mutants due to the outstanding yield. Subsequently, 1-24 was applied in the soil column leaching experiments and removed 45.44% of petroleum hydrocarbons by changing the relevant enzyme activities. Biosurfactant addition and 1-24 inoculation effectively activated a portion of the petroleum hydrocarbons in the soil columns, and 1-24 presented potential as a desired candidate for bioremediation. This is the first report of using ARTP mutagenesis to improve the production of biosurfactants. Simultaneously, we first propose a theoretical system in which the yield of biosurfactant was increased using ARTP mutagenesis for strains and applied the mutants in situ soil bioremediation. This research indicated that the theoretical system was useful in soil columns to simulate field remediation conditions, providing practical references for the bioremediation of contaminated soil.

The Immediate Hotspot of Microbial Nitrogen Cycling in an Oil-Seed Rape (Brassica campestris L.) Soil System Is the Bulk Soil Rather Than the Rhizosphere after Biofertilization.

Biofertilizers are substances that promote plant growth through the efficacy of living microorganisms. The functional microbes comprising biofertilizers are effective mediators in plant-soil systems in the regulation of nitrogen cycling, especially in nitrification repression. However, the deterministic or stochastic distribution of the functional hotspot where microbes are active immediately after biofertilization is rarely investigated. Here, pot experiments with oil-seed rape (Brassica campestris L.) were conducted with various chemical and biological fertilizers in order to reveal the distribution of the hotspot after each fertilization. A stimulated dynamic of the nitrogen cycling-related genes in the bulk soil inferred that the bulk soil was likely to be the hotspot where the inoculated bacterial fertilizers dominated the nitrogen cycle. Furthermore, a network analysis showed that bulk soil microbial communities were more cooperative than those in the rhizosphere after biofertilization, suggesting that the microbiome of the bulk soils were more efficient for nutrient cycling. In addition, the relatively abundant ammonia-oxidizing bacteria and archaea present in the networks of bulk soil microbial communities further indicated that the bulk soil was the plausible hotspot after the application of the biofertilizers. Therefore, our research provides a new insight into the explicit practice of plant fertilization and agricultural management, which may improve the implementational efficiency of biofertilization.

Protistan consumers and phototrophs are more sensitive than bacteria and fungi to pyrene exposure in soil.

The levels of organic pollutants, in particular polycyclic aromatic hydrocarbons (PAHs), are increasing worldwide, yet we lack clarity on how these pollutants affect microbial communities of different trophic levels, including protists, fungi, and bacteria. Herein, we conducted soil microcosm incubation experiments to investigate the effects of pyrene, a typical PAH, on microbial communities along concentration gradients from 0 to 500 mg kg-1 soil. Protistan communities were more sensitive to pollutants than fungal and bacterial communities, and protistan consumers and phototrophs were the dominant trophic functional groups. In addition, by assessing changes in the diversity and structure of the soil microbiome and ecological networks, we found that the microbial communities, including the protistan community and the two trophic communities composed of protists and their prey, were destabilized with increasing stress and pyrene concentrations. We identified links and complicated relationships between phototrophs, bacteria, and consumers in food webs, which explain the importance of protists in stabilizing the microbial community. Collectively, our work provides novel evidence that protists are considerably sensitive to pollution stress, and caution should be exercised in future evaluations of the protistan and multitrophic communities in polluted soil ecosystems.

Evaluation of the current guidelines for antibacterial therapy strategies in patients with cirrhosis or liver failure.

BACKGROUND: Bacterial infections are common complications in patients with cirrhosis or liver failure and are correlated with high mortality. Clinical practice guideline (CPG) is a reference used to help clinicians make decisions. This systematic appraisal aimed to evaluate the methodological quality and summarize the recommendations of reported CPGs in these patients. METHODS: We systematically searched CPGs published from 2008 to 2019. The methodological quality of the included CPGs was assessed using the AGREE II instrument. We extracted and compared recommendations for prophylactic and empirical treatment strategies. RESULTS: Fourteen CPGs with a median overall score of 56.3% were included. The highest domain score was Clarity of Presentation (domain 4, 85.4%), and the lowest was for Stakeholder Involvement (domain 2, 31.3%). Three CPGs had an overall score above 80%, and 6 CPGs had a score above 90% in domain 4. Prophylaxis should be strictly limited to patients with varicose bleeding, low ascites protein levels and a history of spontaneous bacterial peritonitis. Fluoroquinolones (norfloxacin and ciprofloxacin), third-generation cephalosporins (G3) (ceftriaxone and cefotaxime) and trimethoprim-sulfamethoxazole (SXT) are recommended for preventing infections in patients with cirrhosis or liver failure. G3, ß-lactam/ß-lactamase inhibitor combinations (BLBLIs) and carbapenems are recommended as the first choice in empirical treatment according to local epidemiology of bacterial resistance. CONCLUSIONS: The methodological quality of CPGs focused on patients with cirrhosis or liver failure evaluated by the AGREE II instrument is generally poor. Three CPGs that were considered applicable without modification and 6 CPGs that scored above 90% in domain 4 should also be paid more attention to by healthcare practitioners. Regarding recommendations, norfloxacin, ciprofloxacin, ceftriaxone, cefotaxime, and SXT are recommended for prophylactic treatment appropriately. G3, BLBLIs, and carbapenems are recommended for use in empirical treatment strategies.

Ecological selection of bacterial taxa with larger genome sizes in response to polycyclic aromatic hydrocarbons stress.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous priority pollutants that cause great damage to the natural environment and health. Average genome size in a community is critical for shedding light on microbiome's functional response to pollution stress within an environment. Here, microcosms under different concentrations were performed to evaluate the selection of PAHs stress on the average genome size in a community. We found the distinct communities of significantly larger genome size with the increase of PAHs concentration gradients in soils, and consistent trends were discovered in soils at different latitudes. The abundance of Proteobacteria and Deinococcus-Thermus with relatively larger genomes increased along with PAHs stress and well adapted to polluted environments. In contrast, the abundance of Patescibacteria with a highly streamlined and smaller genome decreased, implying complex interactions between environmental selection and functional fitness resulted in bacteria with larger genomes becoming more abundant. Moreover, we confirmed the increased capacity for horizontal transfer of degrading genes between communities by showing an increased connection number per node positively related to the nidA gene along the concentration gradients in the co-occurrence network. Our findings suggest PAHs tend to select bacterial taxa with larger genome sizes, with significant consequences for community stability and potential biodegradation strategies.

RNase Z Oxidative Degradation Impedes tRNA Maturation and is Involved in Streptococcal Translation Regulation in Response to Oxidative Stress.

When encountering oxidative stress, organisms selectively upregulate antioxidant genes and simultaneously suppress the translation of most other proteins. Eukaryotes employ multiple strategies to adjust translation at both the initiation and elongation stages; however, how prokaryotes modulate translation under oxidative stress remains unclear. Here, we report that upon hydrogen peroxide (H2O2) challenge, Streptococcus oligofermentans reduced translation via RNase Z (So-RNaseZ) oxidative degradation, thus hindering tRNA maturation. S. oligofermentans encodes all CCA-less tRNAs that require So-RNaseZ for 3' end maturation. A combination of nonreducing SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC/MS-MS) assays demonstrated that H2O2 oxidation induced Cys38-Cys149 disulfide linkages in recombinant So-RNaseZ protein, and serine substitution of Cys38 or Cys149 abolished these disulfide linkages. Consistently, redox Western blotting also determined intramolecular disulfide-linked So-RNaseZ in H2O2-treated S. oligofermentans cells. The disulfide-linked So-RNaseZ and monomer were both subject to proteolysis, whereas C149S mutation alleviated oxidative degradation of So-RNaseZ, suggesting that H2O2-mediated disulfide linkages substantially contributed to So-RNaseZ degradation. Accordingly, Northern blotting determined that tRNA precursor accumulation and mature tRNA species decrease in H2O2-treated S. oligofermentans. Moreover, reduced overall protein synthesis, as indicated by puromycin incorporation, and retarded growth of S. oligofermentans occurred in an H2O2 concentration-dependent manner. Overexpression of So-RNaseZ not only elevated tRNA precursor processing and protein synthesis but also partly rescued H2O2-suppressed S. oligofermentans growth. Moreover, So-RNaseZ oxidative degradation-mediated translation repression elevated S. oligofermentans survival under high H2O2 stress. Therefore, this work found that So-RNaseZ oxidative degradation-impeded tRNA maturation contributes to streptococcal translation repression and provides the oxidative stress adaptability for S. oligofermentans. IMPORTANCE Translation regulation is a common strategy used by organisms to reduce oxidative damage. Catalase-negative streptococci produce as well as tolerate high levels of H2O2. This work reports a novel translation regulation mechanism employed by Streptococcus oligofermentans in response to H2O2 challenge, in which the key tRNA endonuclease So-RNaseZ is oxidized to form Cys38-Cys149 disulfide linkages and both the disulfide-linked So-RNaseZ and monomers are subject to proteolysis; thus, tRNA maturation, protein translation, and growth are all suppressed. Notably, So-RNaseZ oxidative degradation-mediated translation repression offers oxidative adaptability to S. oligofermentans and enhances its survival against high H2O2 challenge. So-RNaseZ orthologs and H2O2-sensitive cysteines (Cys38 and Cys149) are widely distributed in Streptococcus and Lactococcus species genomes, which also encode all CCA-less tRNAs and lack catalase. Therefore, RNase Z oxidative degradation-based translation regulation could be widely employed by these lactic acid bacteria, including pathogenic streptococci, to cope with H2O2.

Distinct Functions and Assembly Mechanisms of Soil Abundant and Rare Bacterial Taxa Under Increasing Pyrene Stresses.

Elucidating the relative importance of species interactions and assembly mechanisms in regulating bacterial community structure and functions, especially the abundant and rare subcommunities, is crucial for understanding the influence of environmental disturbance in shaping ecological functions. However, little is known about how polycyclic aromatic hydrocarbon (PAH) stress alters the stability and functions of the abundant and rare taxa. Here, we performed soil microcosms with gradient pyrene stresses as a model ecosystem to explore the roles of community assembly in determining structures and functions of the abundant and rare subcommunities. The dose-effect of pyrene significantly altered compositions of abundant and rare subcommunities. With increasing pyrene stresses, diversity increased in abundant subcommunities, while it decreased in the rare. Importantly, the abundant taxa exhibited a much broader niche width and environmental adaptivity than the rare, contributing more to pyrene biodegradation, whereas rare taxa played a key role in improving subcommunity resistance to stress, potentially promoting community persistence and stability. Furthermore, subcommunity co-occurrence network analysis revealed that abundant taxa inclined to occupy the core and central position in adaptation to the pyrene stresses. Stochastic processes played key roles in the abundant subcommunity rather than the rare subcommunity. Overall, these findings extend our understanding of the ecological mechanisms and interactions of abundant and rare taxa in response to pollution stress, laying a leading theoretical basis that abundant taxa are core targets for biostimulation in soil remediation.

Characterization of tetracycline-resistant microbiome in soil-plant systems by combination of H218O-based DNA-Stable isotope probing and metagenomics.

The emergence and spread of antibiotic resistance have been considered as a global health threat. However, effective methods to identify antibiotic-resistant bacteria (ARB) in complex microbial community are lacking, and the potential transmission pathways of ARB and antibiotic resistance genes (ARGs) in the soil-plant system remain scarce. Here in this study, tetracycline was chosen as the target antibiotic due to its globally wide usage and clinical significance. DNA-based stable isotope probing with H218O was applied to identify the tetracycline-resistant bacteria from soil-plant systems. Eighteen-year organic fertilization significantly changed the composition of the tetracycline-resistant microbiome in the soil-wheat system and resulted in a higher relative abundance of ARGs in the wheat endophyte. Rhizosphere harboring the most diverse ARGs and mobile genetic elements was identified as a hot spot for horizontal gene transfer and an important bridge between bulk soil and wheat endophyte. Micrococcaceae and Sphingomonadaceae carrying ARGs associated with abundant mobile genetic elements, were identified as the core bacterial taxa in long-term manure-amended and untreated soil-wheat systems, respectively. This method contributes to a more precise track of ARB in the environment, and our work depicts the high potential of ARG transfer in the rhizosphere mediated by the core species.

Using Child-Pugh Class to Optimize Voriconazole Dosage Regimens and Improve Safety in Patients with Liver Cirrhosis: Insights from a Population Pharmacokinetic Model-based Analysis.

BACKGROUND: Cirrhotic patients are at a high risk of fungal infections. Voriconazole is widely used as prophylaxis and in the treatment of invasive fungal disease. However, the safety, pharmacokinetics, and optimal regimens of voriconazole are currently not well defined in cirrhotic patients. DESIGN: Retrospective pharmacokinetics study. SETTING: Two large, academic, tertiary-care medical center. PATIENTS: Two hundred nineteen plasma trough concentrations (Cmin ) from 120 cirrhotic patients and 83 plasma concentrations from 11 non-cirrhotic patients were included. METHODS: Data pertaining to voriconazole were collected retrospectively. A population pharmacokinetics analysis was performed and model-based simulation was used to optimize voriconazole dosage regimens. RESULTS: Voriconazole-related adverse events (AEs) developed in 29 cirrhotic patients, and the threshold Cmin for AE was 5.12 mg/L. A two-compartment model with first-order elimination adequately described the data. The Child-Pugh class and body weight were the significant covariates in the final model. Voriconazole clearance in non-cirrhotic, Child-Pugh class A and B cirrhotic (CP-A/B) and Child-Pugh class C cirrhotic (CP-C) patients was 7.59, 1.86, and 0.93 L/hour, respectively. The central distribution volume and peripheral distribution volume was 100.8 and 55.2 L, respectively. The oral bioavailability was 91.6%. Model-based simulations showed that a loading dose regimen of 200 mg/12 hours intravenously or orally led to 65.0-75.7% of voriconazole Cmin in therapeutic range on day 1, and the appropriate maintenance dosage regimens were 75 mg/12 hours and 150 mg/24 hours intravenously or orally for CP-A/B patients, and 50 mg/12 hours and 100 mg/24 hours intravenously or orally for CP-C patients. The predicted probability of achieving the therapeutic target concentration for optimized regimens at steady-state was 66.8-72.3% for CP-A/B patients and 70.3-74.0% for CP-C patients. CONCLUSIONS: These results recommended that the halved loading dose regimens should be used, and voriconazole maintenance doses in cirrhotic patients should be reduced to one-fourth for CP-C patients and to one-third for CP-A/B patients compared to that for patients with normal liver function.

Evolution of Homeologous Gene Expression in Polyploid Wheat.

Polyploidization has played a prominent role in the evolutionary history of plants. Two recent and sequential allopolyploidization events have resulted in the formation of wheat species with different ploidies, and which provide a model to study the effects of polyploidization on the evolution of gene expression. In this study, we identified differentially expressed genes (DEGs) between four BBAA tetraploid wheats of three different ploidy backgrounds. DEGs were found to be unevenly distributed among functional categories and duplication modes. We observed more DEGs in the extracted tetraploid wheat (ETW) than in natural tetraploid wheats (TD and TTR13) as compared to a synthetic tetraploid (AT2). Furthermore, DEGs showed higher Ka/Ks ratios than those that did not show expression changes (non-DEGs) between genotypes, indicating DEGs and non-DEGs experienced different selection pressures. For A-B homeolog pairs with DEGs, most of them had only one differentially expressed copy, however, when both copies of a homeolog pair were DEGs, the A and B copies were more likely to be regulated to the same direction. Our results suggest that both cis- and inter-subgenome trans-regulatory changes are important drivers in the evolution of homeologous gene expression in polyploid wheat, with ploidy playing a significant role in the process.