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Background The newly defined superphylum Patescibacteria such as Parcubacteria (OD1) and Microgenomates (OP11) has been found to be prevalent in groundwater, sediment, lake, and other aquifer environments. Recently increasing attention has been paid to this diverse superphylum including > 20 candidate phyla (a large part of the candidate phylum radiation, CPR) because it refreshed our view of the tree of life. However, adaptive traits contributing to its prevalence are still not well known. Results Here, we investigated the genomic features and metabolic pathways of Patescibacteria in groundwater through genome-resolved metagenomics analysis of > 600 Gbp sequence data. We observed that, while the members of Patescibacteria have reduced genomes (~ 1 Mbp) exclusively, functions essential to growth and reproduction such as genetic information processing were retained. Surprisingly, they have sharply reduced redundant and nonessential functions, including specific metabolic activities and stress response systems. The Patescibacteria have ultra-small cells and simplified membrane structures, including flagellar assembly, transporters, and two-component systems. Despite the lack of CRISPR viral defense, the bacteria may evade predation through deletion of common membrane phage receptors and other alternative strategies, which may explain the low representation of prophage proteins in their genomes and lack of CRISPR. By establishing the linkages between bacterial features and the groundwater environmental conditions, our results provide important insights into the functions and evolution of this CPR group. Conclusions We found that Patescibacteria has streamlined many functions while acquiring advantages such as avoiding phage invasion, to adapt to the groundwater environment. The unique features of small genome size, ultra-small cell size, and lacking CRISPR of this large lineage are bringing new understandings on life of Bacteria. Our results provide important insights into the mechanisms for adaptation of the superphylum in the groundwater environments, and demonstrate a case where less is more, and small is mighty. 1EX9Jugkb3j7HLsLG9gAj8 Video abstract.

Thawing Arctic permafrost can induce hydrologic change and alter redox conditions, shifting the balance of soil organic matter (SOM) decomposition. There remains uncertainty about how soil saturation and redox transitions impact dissolved and gas phase carbon fluxes, and efforts to link hydrobiogeochemical processes to ecosystem-scale models are limited. This study evaluates SOM decomposition of Arctic tundra soils using column experiments, water chemistry measurements, microbial community analysis, and a PFLOTRAN reactive transport model. Soil columns from a thermokarst channel (TC) and an upland tundra (UC) were exposed to cycles of saturation and drainage, which controlled carbon emissions. During saturation, an outflow of dissolved organic carbon from the UC soil correlated with elevated reduced iron and decreased pH; during drainage, UC carbon dioxide fluxes were 70% higher than TC fluxes. Intermittent methane release was observed for TC, consistent with higher methanogen abundance. Slower drainage in the TC soil correlated with more subtle biogeochemical changes. PFLOTRAN simulations captured experimental trends in soil carbon fluxes, oxygen concentrations, and water contents. The model was then used to evaluate additional soil water drainage rates. This study emphasizes the importance of considering hydrologic change when evaluating and simulating SOM decomposition in dynamic Arctic tundra environments.

The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1–2wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome- and immunoregulation-based strategies for prevention of stress-related pathologies.

A virus-derived serpin, Serp-1, has proven efficacy in treating inflammatory and coagulation disorders in preclinical and clinical studies. Serp-1 evolved over millions of years to block host immune responses, targeting serine proteases in immune and coagulation pathways. Treatment with PEGylated Serp-1 (PEGSerp-1) protein reduced lung injury in both lupus lung hemorrhage and SARS-CoV-2 models. Here, PEGSerp-1 effects on immune-coagulopathic responses is examined in a mouse colitis model. Inflammatory bowel disease (IBD) is associated with life-threatening complications with severe inflammation, bleeding, vasculitis, cancer and toxic megacolon. Ser ine p rotease cascades activate coagulation and complement pathways throughout the human body and are regulated by in hibitors, termed serpins , that can reduce gut inflammation. Prophylactic PEGSerp-1 significantly improved survival in severe 5% Dextran sodium sulfate (DSS) colitis, reducing inflammation and crypt damage. Colon damage and inflammation were also reduced after either acute colitis induced by 5% DSS or repeat 2% DSS induced colitis. PEGSerp-1 reduced inflammatory M1 macrophage invasion, urokinase-type plasminogen activator receptor (uPAR), fibrinogen and complement on immunohistochemical analysis. PEGSerp-1 reduced uPAR expression in human macrophage, but not colon cells. Here we report analysis of PEGSerp-1 as a tissue and macrophage targeting therapeutic for colitis, reducing immune and coagulation induced damage in the colon.

Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis of DNA from natural microbial communities can be used to accurately identify environmental contaminants, including uranium and nitrate at a nuclear waste site. In addition to contamination, sequence data from the 16S rRNA gene alone can quantitatively predict a rich catalogue of 26 geochemical features collected from 93 wells with highly differing geochemistry characteristics. We extend this approach to identify sites contaminated with hydrocarbons from the Deepwater Horizon oil spill, finding that altered bacterial communities encode a memory of prior contamination, even after the contaminants themselves have been fully degraded. We show that the bacterial strains that are most useful for detecting oil and uranium are known to interact with these substrates, indicating that this statistical approach uncovers ecologically meaningful interactions consistent with previous experimental observations. Future efforts should focus on evaluating the geographical generalizability of these associations. Taken as a whole, these results indicate that ubiquitous, natural bacterial communities can be used as in situ environmental sensors that respond to and capture perturbations caused by human impacts. These in situ biosensors rely on environmental selection rather than directed engineering, and so this approach could be rapidly deployed and scaled as sequencing technology continues to become faster, simpler, and less expensive. IMPORTANCE Here we show that DNA from natural bacterial communities can be used as a quantitative biosensor to accurately distinguish unpolluted sites from those contaminated with uranium, nitrate, or oil. These results indicate that bacterial communities can be used as environmental sensors that respond to and capture perturbations caused by human impacts. Here we show that DNA from natural bacterial communities can be used as a quantitative biosensor to accurately distinguish unpolluted sites from those contaminated with uranium, nitrate, or oil. These results indicate that bacterial communities can be used as environmental sensors that respond to and capture perturbations caused by human impacts.

PurposeIn contaminated streams, understanding the role of streambank and streambed source contributions is essential to developing robust remedial solutions. However, identifying relationships can be difficult because of the lack of identifying signatures in source and receptor pools. East Fork Poplar Creek (EFPC) in Oak Ridge, TN, USA received historical industrial releases of mercury that contaminated streambank soils and sediments. Here, we determined relationships between the contaminated streambank soils and sand-sized streambed sediments.Materials and methodsField surveys revealed the spatial trends of the concentrations of inorganic total mercury (Hg) and methyl mercury (MeHg), Hg lability as inferred by sequential extraction, particle size distribution, and total organic carbon. Statistical tests were applied to determine relationships between streambank soil and streambed sediment properties.Results and discussionConcentrations of Hg in streambank soils in the upper reaches averaged 206 mg kg−1 (all as dry weight) (n = 457), and 13 mg kg−1 in lower reaches (n = 321), while sand-sized streambed sediments were approximately 16 mg kg−1 (n = 57). Two areas of much higher Hg and MeHg concentrations in streambank soils were identified and related to localized higher Hg concentrations in the streambed sediments; however, most of the streambank soils have similar Hg concentrations to the streambed sediments. The molar ratio of Hg to organic carbon, correlation between MeHg and Hg, and particle size distributions suggested similarity between the streambank soils and the fine sand-sized fraction (125–250 μm) collected from the streambed sediments. Mercury in the fine sand-sized streambed sediments, however, was more labile than Hg in the streambank soils, suggesting an in-stream environment that altered the geochemistry of sediment-bound Hg.ConclusionsThis study revealed major source areas of Hg in streambank soils, identified possible depositional locations in streambed sediments, and highlighted potential differences in the stability of Hg bound to streambank soils and sediments. This work will guide future remedial decision making in EFPC and will aid other researchers in identifying source–sink linkages in contaminated fluvial systems.

Subsurface microbial communities mediate the transformation and fate of redox sensitive materials including organic matter, metals and radionuclides. Few studies have explored how changing geochemical conditions influence the composition of groundwater microbial communities over time. We temporally monitored alterations in abiotic forces on microbial community structure using 1L in-field bioreactors receiving background and contaminated groundwater at the Oak Ridge Reservation, TN. Planktonic and biofilm microbial communities were initialized with background water for 4 days to establish communities in triplicate control reactors and triplicate test reactors and then fed filtered water for 14 days. On day 18, three reactors were switched to receive filtered groundwater from a contaminated well, enriched in total dissolved solids relative to the background site, particularly chloride, nitrate, uranium, and sulfate. Biological and geochemical data were collected throughout the experiment, including planktonic and biofilm DNA for 16S rRNA amplicon sequencing, cell counts, total protein, anions, cations, trace metals, organic acids, bicarbonate, pH, Eh, DO, and conductivity. We observed significant shifts in both planktonic and biofilm microbial communities receiving contaminated water. This included a loss of rare taxa, especially amongst members of the Bacteroidetes, Acidobacteria, Chloroflexi, and Betaproteobacteria, but enrichment in the Fe- and nitrate- reducing Ferribacterium and parasitic Bdellovibrio. These shifted communities were more similar to the contaminated well community, suggesting that geochemical forces substantially influence microbial community diversity and structure. These influences can only be captured through such comprehensive temporal studies, which also enable more robust and accurate predictive models to be developed.

As a global environmental pollutant, mercury (Hg) threatens our water resources and presents a substantial risk to human health. The rate and extent of immobilization of Hg 2+ (hereafter, Hg) on engineered sorbents (Thiol-SAMMS®, pine biochar, SediMite™, Organoclay™ PM-199, and quartz sand as a control) was evaluated using flow-through column experiments. The effectiveness of the sorbents was based on (1) the percentage of Hg removed in relation to the total amount of Hg passing the sorbent column, and (2) the rate of Hg uptake compared to the nonreactive tracer bromide (Br − ). All sorbents removed Hg to a certain extent, but none of the sorbents removed all the Hg introduced to the columns. Thiol-SAMMS showed the highest mean percentage of Hg removed (87% ± 2.9%), followed by Organoclay PM-199 (71% ± 0.4%), pine biochar (57% ± 22.3%), SediMite (61% ± 0.8%), and the control quartz sand (11% ± 5.6%). Thiol-SAMMS was the only sorbent to exhibit retardation of Hg in comparison to the conservative tracer Br − . For the remaining sorbents, Br − along with low concentrations of Hg were eluted within the first 3 pore volumes, indicating limited retardation of Hg. Overall, removal of Hg by sorbents was substantial, suggesting that sorbents might be suitable for deployment in contaminated environments. High concentrations of DOM leaching from the soil columns likely influenced the speciation of Hg and inhibited sorption to the sorbents. Incomplete removal of Hg by any sorbent suggests that additional optimization is needed to increase efficiency.

Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or “fine tune” the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.

It has been known for over half a century that mixing an antigen with its cognate antibody in an immune complex (IC) can enhance antigen immunogenicity. However, many ICs produce inconsistent immune responses, and the use of ICs in the development new vaccines has been limited despite the otherwise widespread success of antibody-based therapeutics. To address this problem, we designed a self-binding recombinant immune complex (RIC) vaccine which mimics the larger ICs generated during natural infection. In this study, we created two novel vaccine candidates: 1) a traditional IC targeting herpes simplex virus 2 (HSV-2) by mixing glycoprotein D (gD) with a neutralizing antibody (gD-IC); and 2) an RIC consisting of gD fused to an immunoglobulin heavy chain and then tagged with its own binding site, allowing self-binding (gD-RIC). We characterized the complex size and immune receptor binding characteristics in vitro for each preparation. Then, the in vivo immunogenicity and virus neutralization of each vaccine were compared in mice. gD-RIC formed larger complexes which enhanced C1q receptor binding 25-fold compared to gD-IC. After immunization of mice, gD-RIC elicited up to 1,000-fold higher gD-specific antibody titers compared to traditional IC, reaching endpoint titers of 1:500,000 after two doses without adjuvant. The RIC construct also elicited stronger virus-specific neutralization against HSV-2, as well as stronger cross-neutralization against HSV-1, although the proportion of neutralizing antibodies to total antibodies was somewhat reduced in the RIC group. This work demonstrates that the RIC system overcomes many of the pitfalls of traditional IC, providing potent immune responses against HSV-2 gD. Based on these findings, further improvements to the RIC system are discussed. RIC have now been shown to be capable of inducing potent immune responses to a variety of viral antigens, underscoring their broad potential as a vaccine platform.