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Manna, B.

Publications and source records attributed to Manna, B..

16 recordsLinked to original sources

Redox oscillation frequency reshapes antibiotic resistance-gene expression through metabolic and ecological selection in a freshwater community

Aquatic environments can maintain and express antibiotic resistance genes even without antibiotic pressure, but the conditions that govern their activity remain poorly understood. Redox oscillations are pervasive in natural and engineered waters and strongly alter microbial metabolism, yet whether their frequency shapes resistance expression is unknown. We reanalyzed paired metagenomes and metatranscriptomes from a published chemostat experiment in which a sulfidic stream community was cycled between oxic and anoxic conditions at high, medium and low frequency (HF, MF, LF), with strain-resolved population genomics of the dominant Pseudomonas lineage. Resistance genes were broadly distributed across treatments, whereas transcription concentrated under fast cycling, reaching a median 168 TPM under HF against 38 under LF although no antibiotic was present, so genetic potential and expression diverged. Fast cycling induced ROS-generating flavoproteins, antioxidant defenses and transcription-coupled DNA repair, and Pseudomonas supplied 99% of resistance-gene transcripts under HF, chiefly through its intrinsic efflux systems. Within the dominant Pseudomonas genome, however, the four resistance genes carried no sequence variants under HF, where coverage was deepest, and no fixed difference from the reference in any sample. Genome-wide selection remained purifying throughout (pooled pN/pS 0.72 under HF against 0.12 under LF, both below 1), and the relaxation trended toward redox and central metabolism. Redox frequency therefore raises resistance expression by selecting a metabolically versatile, high-efflux lineage, while the resistance sequences themselves stay conserved. Resistance activity in aquatic systems responds to an abiotic driver, which argues for weighing expression alongside gene presence in environmental surveillance.

microbiology↗

Decoding the Redox-Driven Fate of Organic Micropollutants through Microbial Co-metabolic and ROS-Mediated Degradation in Wastewater

The uncontrolled release of organic micropollutants (OMPs) from wastewater treatment plants highlights a failure to synergize co-metabolic and reactive oxygen species (ROS)-driven biodegradation pathways. Here, we demonstrate that engineered redox cycling--dynamic fluctuations between oxic and anoxic conditions--fundamentally reshapes microbial metabolism and OMP reaction networks to dramatically enhance removal. Using an integrated multi-omics approach centered on paired mass distance (PMD) reactomics, we show that redox cycling increased the removal of 32 diverse OMPs from a baseline of 32% up to 67%. This enhancement was driven by a complete restructuring of degradation mechanisms: cycling stimulated microbial amino acid and fatty acid metabolism by up to 42%, which coupled to controlled ROS production where oxidative pathways (+15.995 Da) accounted for 47% of transformations under intermittent aeration. We mapped distinct "enzymatic fingerprints," with strong correlations (r > 0.7) linking Proteobacteria monooxygenases to oxidative reactions and Rhodobacteraceae dehydrogenases to reductive ones (+2.016 Da), revealing clear functional specialization. Ultimately, the redox regime dictates the entire OMP transformation network topology, shifting pathways from simple hydroxylation to complex, multi-step networks. This work provides a mechanistic framework establishing redox manipulation as a powerful strategy to synergistically activate degradation pathways, allowing existing infrastructure to meet stringent discharge regulations.

bioengineering↗

Heat-tolerant network hub species make freshwater microbial communities resilient to climate warming

Aquatic ecosystems are facing severe threats from climate change, with rising temperatures as a major driving force posing a significant challenge to their ecological balance. Microorganisms constitute the majority of biomass in the water ecosystems and mediate the flux of carbon, nitrogen, sulfate and other essential nutrients. Climate warming profoundly influences microbial communities by shaping their distribution and ecological roles in the ecosystem, and in turn microorganisms play a significant role in climate feedback. The Yellow River, Chinas second-longest river, is crucial for agricultural irrigation and provides drinking water for millions, yet little is known about microbial community adaptations under future warming scenarios in the system. In this study, we analyzed a publicly available metagenomic dataset from Yellow River water samples that were previously subjected to temperature treatments of 23, 26, 29, 32, and 35 degrees Celsius. We employed metagenomic analysis to identify how gradually increasing temperatures affected microbial community profiles. The study identified 140 species tolerant to high temperatures, showing a significant increase in abundance with elevated temperatures. The elevated temperature stress impacted the network properties of microbial communities substantially. Certain temperature-tolerant species were identified as hubs in the network across five temperatures, with their number increasing with temperature. Deltaproteobacteria bacterium was present at all five temperatures, while Parcubacteria bacterium, Parvularcula sp., Phenylobacterium sp., Phycisphaeraceae bacterium, and Sphingobium xenophagum were only present at high temperatures of 32 {degrees}C and 35 {degrees}C. The percentage of taxa nodes connected to tolerant hubs in the overall network rose from 57.48% to 95.94%, indicating the growing importance of these tolerant hubs. The positive connections among these tolerant hubs also increased, with the number of positive edges rising from 1166 to 2811, indicating a potential collaborative relationship among these taxa in response to temperature stress. These findings suggest that tolerant hubs may initially respond to temperature stress and subsequently transfer this function to other species through cooperative interactions. Understanding these microbial dynamics is crucial for developing strategies to maintain freshwater ecosystem health amid climate change.

microbiology↗

Regulating oxygen avaibility mitigates oxidative stresses-induced antibiotic resistance gene expression in E. coli under climate warming

Climate warming presents a critical challenge to global ecosystems, with rising temperatures inducing the emergence of antibiotic resistance genes (ARGs) in aquatic environments. Given the natural correlation between rising temperatures and declining oxygen levels in aquatic systems, we hypothesized that decoupling temperature and oxygen stress would reveal regulatory mechanisms mitigating ARG expression under future warming scenarios. Through transcriptomic analysis of Escherichia coli under temperature upshift (TU), dissolved oxygen upshift (DOU), and dissolved oxygen downshift (DOD), we identified 101 distinct regulons with 8 showing significant regulation (|log2FC| > 1.5). Key regulons (cusR, mhpR, pdhR) exhibited parallel regulation under TU and DOD but opposite patterns under DOU, revealing mechanistic links between temperature and oxygen stress through shared regulatory networks involving oxidative stress regulators (oxyR-metR) and aerobic respiration control (arcA-betI). Evolved strains from controlled temperature-oxygen fluctuations demonstrated sophisticated metabolic reprogramming, including enhanced carbohydrate metabolism, nucleotide biosynthesis, and putrescine degradation. These strains exhibited optimized energy metabolism through reduced downregulation of ATP synthase subunits and NADH dehydrogenase complex genes, preserving electron transport chain function under thermal stress. Simultaneously, they displayed strategic ROS management with reduced upregulation of peroxiredoxin (ahpF) and Cu/Zn-SOD (sodC), while reversing Fe-SOD (sodB) expression patterns. To validate these mechanisms, we conducted independent batch reactor experiments with two dissolved oxygen conditions (2-8 mg/L) using intermittent perturbation patterns. Non-targeted metaproteomic analysis revealed that lowered oxygen levels (2 vs. 8 mg/L) triggered comprehensive reconfiguration of antimicrobial resistance mechanisms, including downregulation of penicillin-binding proteins, alanine racemase, and cationic antimicrobial peptide resistance systems, while modulating two-component regulatory networks. Our findings reveal coordinated regulatory networks optimizing energy metabolism, ROS management, and antibiotic resistance, suggesting oxygen management strategies could mitigate climate warming effects on antibiotic resistance in aquatic environments.

microbiology↗

Linking Oxygen-Induced Oxidative Stress to Resource Recovery by Enhancing the Production of Extracellular Polymeric Substances in Activated Sludge Microbial Communities

As the global transition toward circular wastewater treatment intensifies, extracellular polymeric substances (EPS) have emerged as valuable targets for resource recovery. Although most efforts have focused on aerobic granular sludge, conventional activated sludge systems, which account for most global wastewater treatment, remain underexploited for EPS recovery. Building on the established link between oxidative stress and EPS biosynthesis in pure strains, we propose that strategically manipulating oxygen exposure patterns to intensify oxidative stress in activated sludge microbial communities could enhance EPS production. To test this, we applied continuous oxygen perturbation under aerobic exposure to intensify oxidative stress. Compared to a stable oxygen condition simulating typical wastewater aeration, the perturbation considerably enhanced EPS yield to 74.4{square}mg/L/day, a 90.5% increase over the stable condition (39.0{square}mg/L/day). To validate the role of oxidative stress in EPS enhancement, intermittent anoxic phases were introduced into the perturbation pattern to relieve oxidative stress, causing the EPS-enhancing effect to disappear, with yield dropping to 9.8{square}mg/L/day. Mechanistically, intensified oxidative stress under aerobic continuous perturbation was primarily driven by elevated reducing substrates for non-respiratory flavoenzymes, exemplified by glutamate synthase, glutathione reductase, and dihydrolipoamide dehydrogenase, which are prone to generate H2O2 as an unintended metabolic byproduct. Among the multiple microbial groups contributing to H2O2 production, Methylophilaceae, Comamonadaceae, and Rhodobacteraceae were distinguished by simultaneously exhibiting upregulation of EPS biosynthesis proteins, suggesting that taxa within these families collectively mediated both H2O2 production and EPS enhancement. By modulating aeration, this study offers a chemical-free, controllable strategy for enhancing EPS production within conventional activated sludge systems. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/651171v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1f52710org.highwire.dtl.DTLVardef@1d7b36corg.highwire.dtl.DTLVardef@4484b5org.highwire.dtl.DTLVardef@64979f_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Microbial Degradation of Contaminants of Emerging Concern by Pseudomonas putida in Wastewater Treatment Plants

Contaminants of Emerging Concern (CECs) are a class of contaminants that are commonly found in urban wastewater treatment plants (WWTP) at low concentrations. These compounds include antibiotic drugs, personal care products, and industrial chemicals, which are widely used in modern society. Although they provide undeniable benefits in our daily lives, their accumulation in the environment poses a significant risk to human health and the ecosystem. Due to the incomplete removal of these compounds by traditional WWTPs, there is a need to understand the interactions between microbes and CECs to develop effective solutions to this environmental challenge. Pseudomonas putida is a bacterium commonly found in water-related habitats, including freshwater streams, forests, and WWTPs. It is known for its ability to degrade various organic compounds, making it a suitable model for understanding the linkages between bacterial enzymes and CECs found in WWTPs. In this study, isolated Pseudomonas putida strain KT2440 was cultured in lab-scale reactors to mimic the WWTP environment. The degradation of this isolated strain towards different groups of CECs were studied over a 24-hour period using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Mass spectrometry-based quantitative proteomics was also performed at different sampling points to establish a linkage between the enzyme expression profile of this strain and its degradation of CECs via bioinformatics analysis. The results of this study demonstrated that Pseudomonas putida KT2440 is capable of degrading atrazine, acetamiprid, carbendazim, diclofenac acid, erythromycin, and sulfamethazine at lab scale. At the 20-hour time point, the enzyme expression profile indicated a high protein abundance of various oxidoreductases that could explain the observed CEC degradation.The studys findings provide important insights into the potential of Pseudomonas putida as a bioremediation agent for CECs in WWTPs. The degradation of CECs by Pseudomonas putida KT2440 is a significant contribution to the bioremediation process, and its enzyme expression profile can serve as a case study for more complex interactions of microbes and CECs in real WWTPs. Furthermore, this study supports the potential of Pseudomonas putida as a promising strain for various bioremediation applications. Finally, this studys results can help develop more efficient and effective methods for removing CECs from wastewater, which can contribute to the protection of public health and the environment.

microbiology↗

Intermittent Perturbation with High-Frequency Aerobic-Anoxic Cycling Enhances N2O Reductase Activity during Wastewater Treatment

Nitrous oxide (N2O) emissions from wastewater treatment plants, with a warming potential 298 times that of CO2, pose a significant challenge to lowering their carbon footprint. Current mitigation strategies focus on limiting N2O formation during nitrification and denitrification but overlook microbial reduction mechanisms. This study examines the potential for enhancing nitrous oxide reductase (NosZ) activity to reduce N2O to N2. We hypothesize that strategic oxygen manipulation can enhance N2O destruction by continuous NosZ expression and enable NosZ activation in microorganisms with superior NosZ capabilities. We assess microbial community function and metabolic regulation using metagenomics and metaproteomics to clarify the effect of intermittent aeration regimes on N2O emission. Intermittent aeration with periodic anoxic exposure significantly reduced N2O emissions with 71% nitrogen removal by enhancing the metabolic activity of Hyphomicrobium. NosZ activity increased by 4- to 6.5-fold after system adaptation to oxygen modulations, compared to continuous oxic-anoxic cycling without the anoxic phase. The latter resulted in increased N2O emissions due to suppressed NosZ activity and higher N2O production from Methylobacillus, which uses nitric oxide as an alternative electron acceptor. Our finding that strategic oxygen manipulation can energize N2O destruction lays the foundation for developing next-generation wastewater treatment technologies for mitigating N2O emissions.

microbiology↗

Investigating Potential Microbial Contributors to Enhanced Metabolite Production under Oxygen Perturbations: An Integrated Metagenomic and Metabolomic Approach

The specific impacts of oxygen perturbation on microbial communities and their synthesis of metabolites remain unclear. We systematically explored how oxygen perturbations alter microbial growth, subsequently affecting the abundance of functional genes and promoting the synthesis of metabolites such as amino acids. Analysis of microbial community structure indicates dynamic stability under oxygen perturbations, with only a fraction of the microbial abundance being altered. By comparing the abundance of functional genes with metabolic features, we revealed how changes in the microbial community impact the overall system performance. Amino acid biosynthesis has an enhanced potential under conditions of oxygen perturbation. Through biological and statistical correlation analyses, we identified microbial species significantly correlated with the efficiency of target metabolic reactions under oxygen perturbations. Mycolicibacterium madagascariense, Mycolicibacterium fortuitum, and Burkholderia pseudomallei displayed strong associations with proline and tryptophan synthesis reactions. Moreover, the abundance of microbial genera including Labrys, Actinomyces, and Nitrosopumilus exhibited a highlysignificant positive correlation with metabolite abundance in enriched metabolic pathways under oxygen perturbations. These results suggest that microbial systems might achieve dynamic stability in community structure under oxygen perturbations, while exhibiting slightly differential metabolic potentials. Notably, enhanced efficiency in amino acid biosynthesis could help to assimilate more carbon and nitrogen resources in activated sludge during wastewater treatment. SYNOPSISWe provide an in-depth investigation into the impact of oxygen perturbations on microbial growth in activated sludge systems and the subsequent variations in the abundance of metabolic genes. Our research highlights the potential for subtle changes in amino acid biosynthesis and identifies key microbial species associated with synthesis efficiency. These insights into the dynamic stability and differentiated metabolic potentials of microbial communities during oxygen perturbations can inform the development of more effective resource recovery strategies.

microbiology↗

Assessing Oxygen Perturbation and Over-Aeration Impacts on Soluble Microbial Products (SMP) Production and Release in Activated Sludge Systems

Understanding the interplay between oxygen conditions and microbial activities in an activated sludge system is crucial for the optimization of wastewater treatment processes. This study explores the influence of various aeration patterns and dissolved oxygen (DO) levels on the microbial metabolic activities, with a particular focus on the synthesis and release of soluble microbial products (SMP), and the regulation of key metabolic genes and enzymes. The activated sludge system underwent different aeration patterns, including constant aeration, continuous perturbation, and intermittent perturbation under two distinct DO levels of 2mg/L and 8mg/L. We employed a combination of multi-omics techniques (metagenomics, metaproteomics, and metabolomics) along with chemical analytical methods for comprehensive sample analysis. Our results reveal an increased intracellular accumulation of amino acids and enhanced release of protein under the conditions of oxygen perturbation. Furthermore, elevated DO levels fostered the accumulation of poly-3-hydroxybutyrate intracellularly and the release of protein and fatty acids as SMP. This outcome is associated with the abundance of key metabolic genes and enzymes, thereby highlighting the metabolic flexibility of microbes under different oxygen conditions. These findings offer valuable insights into microbial metabolic dynamics under varying oxygen conditions, thereby providing guidance for more efficient and sustainable strategies in wastewater treatment and resource recovery. SYNOPSISThis study explores the complex interplay between varying oxygen conditions and microbial activity in activated sludge systems, focusing on the impact on the synthesis and release of soluble microbial products (SMP). Findings highlight the significant influence of oxygen perturbation and dissolved oxygen levels on protein synthesis and fatty acid metabolic processes.

microbiology↗

Resource Recovery from Wastewater By Directing Microbial Metabolism Toward Production of Value-added Biochemicals

Transitioning wastewater treatment from mere pollutant removal to resource recovery necessitates exploiting the metabolic capabilities of microbial communities. Studies suggest that under low-oxygen conditions, microbes activate oxygen-responsive regulons that suppress the tricarboxylic acid (TCA) cycle, diverting carbon flux towards biosynthetic pathways and accumulating valuable organic metabolites. We hypothesized that dynamically altering dissolved oxygen levels in activated sludge would disrupt aerobic metabolic equilibrium, enhancing the production of valuable biochemicals like amino acids and fatty acids. To test this, batch experiments were conducted with activated sludge under constant aeration and rapid cycling between oxygen-rich and oxygen-poor states. Fluctuating oxygen concentrations between 0 and 2 mg/L significantly increased valuable biochemical production compared to constant aeration (P<0.05). Continuous oxygen perturbations increased free amino acids by 35.7{+/-}7.6% and free fatty acids by 76.4{+/-}13.0%, while intermittent perturbations with anoxic periods enhanced free amino acids by 42.4{+/-}8.1% and free fatty acids by 39.3{+/-}7.7%. Notably, 14 standard amino acids showed significant increases, and most fatty acids had carbon chain lengths between C12-C22. Mechanistically, compared to stable oxygen, oxygen perturbations activated the FNR and ArcA regulons, resulting in lower relative abundances of TCA cycle enzymes such as malate dehydrogenase, isocitrate dehydrogenase, and 2-oxoglutarate dehydrogenase, while higher relative abundances of amino acid (ilv cluster) and fatty acid (acc cluster) biosynthetic enzymes. Our findings demonstrate that introducing controlled oxygen fluctuations in wastewater treatment can enhance the biochemical value of activated sludge with minimal process modifications, facilitating resource recovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/614227v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@181590corg.highwire.dtl.DTLVardef@fd51c3org.highwire.dtl.DTLVardef@102ddd1org.highwire.dtl.DTLVardef@130dc73_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Microbial Metabolic Enzymes, Pathways and Microbial Hosts for Co-Metabolic Degradation of Organic Micropollutants in Wastewater

Organic micropollutants (OMPs) in wastewater present significant environmental challenges, but effective removal strategies are hindered by our limited understanding of their co-metabolic biodegradation. We aim to elucidate the microbial enzymes, metabolic pathways, and community members involved in OMP co-metabolic degradation, thereby paving the way for more effective wastewater treatment strategies. We integrated multi-omics (metagenomics, metaproteomics, and metabolomics) and functional group analysis to investigate 24 OMPs under three aeration conditions. Our findings reveal that oxidoreductases, particularly cytochrome P450s and peroxidases, are crucial for recalcitrant OMPs containing halogen groups (-Cl, -F) like fluoxetine and diuron. Hydrolases, including amidases, are instrumental in targeting amide-containing (-CONH2) OMPs such as bezafibrate and carbamazepine. Regarding microbial metabolism involved in OMP co-metabolic degradation, we found that amino acid metabolism is crucial for degrading amine-containing (-NH2) OMPs like metoprolol and citalopram. Lipid metabolism, particularly for fatty acids, contributes to the degradation of carboxylic acid (-COOH) containing OMPs such as bezafibrate and naproxen. Finally, with Actinobacteria, Bacteroidetes, and Proteobacteria emerging as primary contributors to these functionalities, we established connections between OMP functional groups, degradation enzymes, metabolic pathways, and microbial phyla. Our findings provide generalized insights into structure-function relationships in OMP co-metabolic degradation, offering the potential for improved wastewater treatment strategies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/611302v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1785fd8org.highwire.dtl.DTLVardef@1dc732dorg.highwire.dtl.DTLVardef@d9eaborg.highwire.dtl.DTLVardef@2c2813_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Short-Term Warming Induces Cyanobacterial Blooms and Antibiotic Resistance in a Freshwater Lake as Revealed by Metagenomics Analysis

Climate change poses significant risks to freshwater ecosystems, potentially exacerbating harmful cyanobacterial blooms and antibiotic resistance. We investigated these dual threats in Cosseys Reservoir, New Zealand, by simulating short-term warming scenarios and assessing the role of oxidative stress. Microcosms were subjected to Base (22{degrees}C), Normal (24{degrees}C), and projected Future (27{degrees}C) temperatures, with additional treatments including reactive oxygen species (ROS). Metagenomic analysis revealed substantial restructuring of microbial communities under warming conditions. Cyanobacterial abundance increased from 6.11% (initial) to 20.53% at 24{degrees}C and 10.66% at 27{degrees}C. Notably, ROS addition mimicked the effects of temperature increase on cyanobacterial proliferation. Toxin-producing families, including Microcystaceae and Nostocaceae, proliferated significantly. The microcystin synthesis gene (mcy) showed a strong positive association (R{superscript 2} = 0.88) with cyanobacterial abundance. Moreover, cyanobacteria exhibited enhanced nutrient acquisition (pstS gene, R{superscript 2} = 0.69) and upregulated nitrogen metabolism pathways under warming conditions. Concurrently, we observed a marked increase in antibiotic resistance gene (ARG) abundance with rising temperatures. The relative abundance of multidrug resistance genes was consistently high across all conditions (50.82 % of total ARGs). ROS stress further intensified ARG proliferation, particularly for efflux pump genes (e.g., acrB, adeJ, ceoB, emrB, MexK, muxB). Co-association network analysis identified key antibiotic-resistant bacteria (e.g., Streptococcus pneumoniae, Acinetobacter baylyi) and ARGs (e.g., acrB, MexK, rpoB2, bacA) central to resistance dissemination under warming conditions. This study demonstrates that even modest temperature increases (2-5{degrees}C) can promote both cyanobacterial blooms and antibiotic resistance in freshwater ecosystems over short time scales. The synergistic effects of temperature and oxidative stress underscore the complex challenges posed by climate change to water quality and public health. HighlightsO_LIShort-term warming promotes toxic cyanobacteria and antibiotic resistance in freshwater. C_LIO_LIHarmful cyanobacteria and their metabolic potential increase under warming conditions. C_LIO_LIReactive oxygen species mimic and exacerbate temperature effects. C_LIO_LIOxidative stress response genes strongly correlate with ARG abundance. C_LIO_LICo-association networks identify key host pathogen central to resistance spread. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/602497v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@157fc25org.highwire.dtl.DTLVardef@16b1103org.highwire.dtl.DTLVardef@29fa6eorg.highwire.dtl.DTLVardef@1f88650_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

ROS-Induced Oxidative Stress Causes Enrichment and Emergence of Antibacterial Resistance in Conventional Activated Sludge Process

Since the Great Oxidation Event 2.4 billion years ago, microorganisms have evolved sophisticated responses to oxidative stress. These ancient adaptations remain relevant in modern engineered systems, particularly in conventional activated sludge (CAS) processes, which serve as significant reservoirs of antibiotic resistance genes (ARGs). While ROS-induced stress responses are known to promote ARG enrichment/emergence in pure cultures, their impact on ARG dynamics in wastewater treatment processes remains unexplored. Shotgun-metagenomics analysis of two hospital wastewater treatment plants showed that only 35-53% of hospital effluent resistome was retained in final effluent. Despite this reduction, approximately 30% of ARGs in CAS showed higher abundance than upstream stages, of which 22% emerged de novo. Beta-lactamases and efflux pumps constituted nearly 50% of these enriched ARGs. These ARGs exhibited significant correlations (p < 0.05) with ROS stress response genes (oxyR, soxR, sodAB, katG and ahpCF). The CAS resistome determined 58-75% of the effluent ARG profiles, indicating treatment processes outweigh influent composition in shaping final resistome. Proof-of-concept batch reactor experiments confirmed increased ROS and ARG levels under high dissolved oxygen (8 mg/L) compared to low oxygen (2 mg/L). Untargeted metaproteomics revealed higher expression of resistant proteins (e.g., OXA-184, OXA-576, PME-1, RpoB2, Tet(W/32/O)) under elevated ROS levels. Our findings demonstrate that CAS processes actively shape effluent resistome through ROS-mediated selection, indicating that treatment processes, rather than initial wastewater composition, determine final ARG profiles. This study indicates that the emergence of ARGs needs to be considered as an integral aspect of wastewater treatment design and operation to prevent antibiotic resistance dissemination. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/585878v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@379e42org.highwire.dtl.DTLVardef@1772832org.highwire.dtl.DTLVardef@1f025d7org.highwire.dtl.DTLVardef@144507a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIApproximately 30% of ARGs enriched in CAS versus upstream stages, of which 22% emerged de novo C_LIO_LIBeta-lactamases and efflux pumps comprise [~]50% of enriched ARGs in CAS C_LIO_LICAS resistome shapes 58-75% of effluent ARGs, outweighing influent composition C_LIO_LIHigh DO levels increase ROS production and ARG abundance in CAS systems C_LIO_LIMetaproteomics confirms higher expression of resistant proteins under elevated ROS levels C_LI

genomics↗

Rational engineering of a β-glucosidase (H0HC94) from glycosyl family I (GH1) to improve catalytic performance on cellobiose

The conversion of lignocellulosic feedstocks by cellulases to glucose is a critical step in biofuel production. {beta}-glucosidases catalyze the final step in cellulose breakdown, producing glucose, and is often the rate-limiting step in biomass hydrolysis. Rationally engineering previously characterized enzymes may be one strategy to increase catalytic activity and the efficiency of cellulose hydrolysis. The specific activity of most natural and engineered {beta}-glucosidase is higher on the artificial substrate p-Nitrophenyl {beta}-D-glucopyranoside (pNPGlc) than on the natural substrate, cellobiose. Based on our hypothesis of increasing catalytic activity by reducing the interaction of residues present near the active site tunnel entrance with glucose without disturbing any existing interactions with cellobiose, we report an engineered {beta}-glucosidase (Q319A H0HC94) with a 1.8-fold specific activity increase (366.3 {+/-} 36 {micro}mol/min/mg), an almost 1.5-fold increase in kcat (340.8 {+/-} 27 s-1), and a 3-fold increase in Q319A H0HC94 cellobiose specificity (236.65 mM-1 s-1) over HOHC94. Molecular dynamic simulations and protein structure network analysis indicate that Q319A significantly increased the dynamically stable communities and hub residues, leading to a change in enzyme conformation and higher enzymatic activity. This study shows the impact of rational engineering of non-conserved residue to increase {beta}-glucosidase substrate accessibility and enzyme specificity. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/505235v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@392a36org.highwire.dtl.DTLVardef@10252d4org.highwire.dtl.DTLVardef@18c1749org.highwire.dtl.DTLVardef@4cc8c6_HPS_FORMAT_FIGEXP M_FIG A rationally engineered -glucosidase with a 1.5-fold increase in kcat, and a 3-fold increase in cellobiose specificity over the wild-type C_FIG

bioengineering↗

L-norepinephrine induces ROS formation but alters microbial community composition by altering cellular metabolism

Neuroendocrine compounds discharged into wastewater systems represent an emerging challenge at the intersection of human physiology and environmental microbiology. L-norepinephrine (L-NE) L-NE, which has been recognized to potentiate growth of human and animal bacterial pathogens, is discharged in sewage through urine and feces. While extensive pure culture studies have established L-NEs capacity to modulate bacterial virulence through iron acquisition and quorum sensing pathways, its impact on complex microbial communities, where intricate metabolic networks and interspecies interactions dominate, remains largely unexplored. This knowledge gap is particularly critical as urbanization drives increasing neuroendocrine compound loads in wastewater influents in metropolitan areas. Through parallel treatments of L-NE (1x10{square}{square} to 1x10{square}{square} M), dextrose, and H{square}O{square} in municipal and agricultural wastewater communities, we uncovered sophisticated metabolic and regulatory mechanisms that challenge the conventional understanding of microbial substrate utilization. Despite containing 10-fold less carbon, L-NE treatments achieved superior growth (10{square} CFU mL{square}{superscript 1}) while maintaining Pseudomonadaceae-dominated communities. Targeted metaproteomics revealed coordinated upregulation of oxidative stress genes (oxyR, soxRS) and antioxidant enzymes, while proteome-constrained metabolic modeling demonstrated distinct pathway modulation in central carbon and nitrogen metabolism. Notably, when compared to dextrose-supplemented controls representing typical carbon substrate utilization, L-NE treatments showed similar taxonomic profiles without preferential enrichment of known pathogenic families. However, L-NE significantly enhanced autoinducer gene (luxS, qseC) expression, suggesting increased virulence potential through community-level metabolic reprogramming. These findings reveal L-NE as a potent modulator of microbial community dynamics in engineered ecosystems, with important implications for treatment process stability and downstream environmental impacts. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/482069v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1d80968org.highwire.dtl.DTLVardef@51cb63org.highwire.dtl.DTLVardef@b37org.highwire.dtl.DTLVardef@e07503_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOTOC FigureC_FLOATNO C_FIG

microbiology↗

An allosteric hot-spot in the tandem-SH2 domain of ZAP-70 regulates T-cell signaling

T-cell receptor (TCR) signaling is initiated by recruiting ZAP-70 to the cytosolic part of TCR. ZAP-70, a non-receptor tyrosine kinase, is composed of an N-terminal tandem SH2 (tSH2) domain connected to the C-terminal kinase domain. The ZAP-70 is recruited to the membrane through binding of tSH2 domain and the doubly-phosphorylated ITAM motifs of CD3 chains in the TCR complex. Our results show that the tSH2 domain undergoes a biphasic structural transition while binding to the doubly-phosphorylated ITAM-{zeta}1 peptide. The C-terminal SH2 domain binds first to the phosphotyrosine residue of ITAM peptide to form an encounter complex leading to subsequent binding of second phosphotyrosine residue to the N-SH2 domain. We decipher a network of non-covalent interactions that allosterically couple the two SH2 domains during binding to doubly-phosphorylated ITAMs. Mutation in the allosteric network residues, for example, W165C, uncouples the formation of encounter complex to the subsequent ITAM binding thus explaining the altered recruitment of ZAP-70 to the plasma membrane causing autoimmune arthritis in mice. The proposed mechanism of allosteric coupling is unique to ZAP-70, which is fundamentally different from Syk, a close homolog of ZAP-70 expressed in B-cells. SignificanceT-cell and B-cell signaling is initiated by the same family of non-receptor tyrosine kinases, ZAP-70 and Syk, respectively. ZAP-70 and Syk share homologous sequence and similar structural architecture, yet the two kinases differ in their mode of ligand recognition. ZAP-70 binds cooperatively to its ligand, whereas Syk binds uncooperatively. Spontaneous mutation (W165C) in the regulatory module of ZAP-70 impairs T-cell signaling causes autoimmune arthritis in SKG mice, the mechanism of which is unknown. We showed that ZAP-70 regulatory module undergoes a biphasic structural transition while binding to its ligand, which is fundamentally different from Syk. We presented a molecular mechanism of cooperativity in ZAP-70 regulatory module that explains altered ligand binding by ZAP-70 mutant found in SKG mice.

biochemistry↗