ABSTRACT
This study presents the utilization of a novel, highly lipophilic nitric oxide (NO) donor molecule, S-nitroso-1-adamantanethiol (SNAT), for developing an NO-emitting polymer surface aimed at preventing thrombus formation and bacterial infection in extracorporeal circuits (ECCs). S-nitroso-1-adamantanethiol, a tertiary nitrosothiol-bearing adamantane species, was synthesized, characterized, and used to impregnate polyvinyl chloride (PVC) tubing for subsequent in vivo evaluation. The impregnation process with SNAT preserved the original mechanical strength of the PVC. In vitro assessments revealed sustained NO release from the SNAT-impregnated PVC tubing (iSNAT), surpassing or matching endothelial NO release levels for up to 42 days. The initial NO release remained stable even after 1 year of storage at -20°C. The compatibility of iSNAT with various sterilization techniques (OPA Plus, hydrogen peroxide, EtO) was tested. Acute in vivo experiments in a rabbit model demonstrated significantly reduced thrombus formation in iSNAT ECCs compared with controls, indicating the feasibility of iSNAT to mitigate coagulation system activation and potentially eliminate the need for systemic anticoagulation. Moreover, iSNAT showed substantial inhibition of microbial biofilm formation, highlighting its dual functionality. These findings underscore the promising utility of iSNAT for long-term ECC applications, offering a multifaceted approach to enhancing biocompatibility and minimizing complications.
ABSTRACT
Though sterile diet, post-transplantation surgery is a clinical strategy for patient care to prevent the infiltration of gut pathogens, less is known about its effects on the gut microbiome. Here, the gut microbiome dynamics of leukemia patients following a 120-day "sterile-normal" diet strategy posthematopoietic cell transplantation are examined. In contrast to the traditional idea, a sterile diet leads to the lowest gut microbiota diversity (p < 0.05) and short-chain fatty acids, promoted the proliferation of potential pathogens such as Streptococcus (up by 16.93%) and Lactobacillus (up by 40.30%), and 43.32% reduction in nodes and an 85.33% reduction in edges within the microbial interaction's network. Interestingly, a normal diet allows the gut microbiome recovery and significantly promotes the abundance of beneficial bacteria. These results indicate that a sterile diet leads to a collapse of the patient's gut microbiome and promoted the proliferation of potential pathogens. This assay is a starting point for a more sophisticated assessment of the effects of a sterile diet. The work also suggests a basic principle for the re-establishment of microbial equilibrium that supplementation of microbial taxa may be the key to the restoration of the degraded ecosystem.
ABSTRACT
BACKGROUNDS: Infection during pregnancy is a significant public health concern due to the increased risk of adverse birth outcomes. Group B Streptococcus or Streptococcus agalactiae (GBS) stands out as a major bacterial cause of neonatal morbidity and mortality. We aimed to explore the involvement of reactive oxygen species (ROS) and oxidative stress pathways in pro-inflammatory responses within human fetal membrane tissue, the target tissue of acute bacterial chorioamnionitis. METHODS: We reanalyzed transcriptomic data from fetal membrane explants inoculated with GBS to assess the impact of GBS on oxidative stress and ROS genes/pathways. We conducted pathway enrichment analysis of transcriptomic data using the Database for Annotation, Visualization and Integrated Discovery (DAVID), a web-based functional annotation/pathway enrichment tool. Subsequently, we conducted ex vivo experiments to test the hypothesis that antioxidant treatment could inhibit pathogen-stimulated inflammatory responses in fetal membranes. RESULTS: Using DAVID analysis, we found significant enrichment of pathways related to oxidative stress or ROS in GBS-inoculated human fetal membranes, for example, "Response to Oxidative Stress" (FDR = 0.02) and "Positive Regulation of Reactive Oxygen Species Metabolic Process" (FDR = 2.6*10-4 ). There were 31 significantly changed genes associated with these pathways, most of which were upregulated after GBS inoculation. In ex vivo experiments with choriodecidual membrane explants, our study showed that co-treatment with N-acetylcysteine (NAC) effectively suppressed the release of pro-inflammatory cytokines (IL-6, IL-8, TNF-α) and prostaglandin PGE2, compared to GBS-treated explants (p < .05 compared to GBS-treated samples without NAC co-treatment). Furthermore, NAC treatment inhibited the release of cytokines and PGE2 stimulated by lipoteichoic acid (LTA) and lipopolysaccharide (LPS) in whole membrane explants (p < .05 compared to LTA or LPS-treated samples without NAC co-treatment). CONCLUSIONS: Our study sheds light on the potential roles of ROS in governing the innate immune response to GBS infection, offering insights for developing strategies to mitigate GBS-related adverse outcomes.
Subject(s)
Chorioamnionitis , Streptococcal Infections , Teichoic Acids , Pregnancy , Female , Infant, Newborn , Humans , Cytokines/metabolism , Lipopolysaccharides/pharmacology , Antioxidants/pharmacology , Antioxidants/metabolism , Reactive Oxygen Species/metabolism , Acetylcysteine/pharmacology , Acetylcysteine/metabolism , Dinoprostone/metabolism , Prostaglandins/metabolism , Streptococcus agalactiae , Extraembryonic Membranes/metabolismABSTRACT
Quantifying atmospheric loadings of total phosphorus (TP) to freshwater environments is essential to improve understanding of its fate and transport, and to mitigate the effects of excessive levels in freshwater ecosystems. To date, atmospheric deposition of TP in the U.S. is poorly characterized due to the lack of long-term deposition observations. Here, we integrate several historical datasets to develop an estimate of dry and wet deposition to the Great Lakes region. For dry deposition, we use TP concentrations in fine particulate matter (PM2.5) samples from fourteen land-based IMPROVE sites (2013-2020) upwind of the Great Lakes to provide new fine particle phosphorus dry deposition estimates. For wet deposition, we use TP concentrations in wet-only precipitation samples collected at eleven land-based sites (2001-2009) in the Great Lakes region. For both wet and dry deposition, a seasonal cycle is evident with higher concentrations in warmer and wetter months when compared to colder months. Additionally, there is an increasing gradient from north to south in wet deposition, likely driven by both higher precipitation and increased emissions near southern sites. Despite different sampling time periods, these updated observations can provide further constraints on the TP loadings to each of the five Great Lakes. We estimate annual deposition of TP to Lakes Superior, Michigan, Huron, Erie and Ontario at 526, 702, 495, 212, and 185 MTA per year, which is lower than prior estimates for Lakes Superior, Erie and Ontario, comparable for Lake Huron, and about two times greater for Lake Michigan. When considering only the contribution of fine particulate PM to the dry deposition, wet deposition dominated over dry at all lakes except for Lake Huron. However, prior global estimates suggest greater contributions from larger particles (PM10 and PM100), yet observations to validate these estimates over the Great Lakes are not available. Our findings indicate that dry deposition of a range of particle sizes are needed to constrain the total atmospheric deposition of TP over the Great Lakes.
ABSTRACT
BACKGROUND: Evidence is needed on the presence of SARS-CoV-2 in various types of environmental samples and on the estimated transmission risks in non-healthcare settings on campus. OBJECTIVES: The objective of this research was to collect data on SARS-CoV-2 viral load and to examine potential infection risks of people exposed to the virus in publicly accessible non-healthcare environments on a university campus. METHODS: Air and surface samples were collected using wetted wall cyclone bioaerosol samplers and swab kits, respectively, in a longitudinal environmental surveillance program from August 2020 until April 2021 on the University of Michigan Ann Arbor campus. Quantitative rRT-PCR with primers and probes targeting gene N1 were used for SARS-CoV-2 RNA quantification. The RNA concentrations were used to estimate the probability of infection by quantitative microbial risk assessment modeling and Monte-Carlo simulation. RESULTS: In total, 256 air samples and 517 surface samples were collected during the study period, among which positive rates were 1.6% and 1.4%, respectively. Point-biserial correlation showed that the total case number on campus was significantly higher in weeks with positive environmental samples than in non-positive weeks (p = 0.001). The estimated probability of infection was about 1 per 100 exposures to SARS-CoV-2-laden aerosols through inhalation and as high as 1 per 100,000 exposures from contacting contaminated surfaces in simulated scenarios. SIGNIFICANCE: Viral shedding was demonstrated by the detection of viral RNA in multiple air and surface samples on a university campus. The low overall positivity rate indicated that the risk of exposure to SARS-CoV-2 at monitored locations was low. Risk modeling results suggest that inhalation is the predominant route of exposure compared to surface contact, which emphasizes the importance of protecting individuals from airborne transmission of SARS-CoV-2 and potentially other respiratory infectious diseases. IMPACT: Given the reoccurring epidemics caused by highly infectious respiratory viruses in recent years, our manuscript reinforces the importance of monitoring environmental transmission by the simultaneous sampling and integration of multiple environmental surveillance matrices for modeling and risk assessment.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Motor Vehicles , RNA, Viral/analysis , Respiratory Aerosols and Droplets , UniversitiesABSTRACT
Airborne bacteria may absorb the substance from the atmospheric particles and play a role in biogeochemical cycling. However, these studies focused on a few culturable bacteria and the samples were usually collected from one site. The metabolic potential of a majority of airborne bacteria on a regional scale and their driving factors remain unknown. In this study, we collected particulates with aerodynamic diameter ≤2.5 µm (PM2.5) from 8 cities that represent different regions across China and analyzed the samples via high-throughput sequencing of 16S rRNA genes, quantitative polymerase chain reaction (qPCR) analysis, and functional database prediction. Based on the FAPROTAX database, 326 (80.69%), 191 (47.28%) and 45 (11.14%) bacterial genera are possible to conduct the pathways of carbon, nitrogen, and sulfur cycles, respectively. The pathway analysis indicated that airborne bacteria may lead to the decrease in organic carbon while the increase in ammonium and sulfate in PM2.5 samples, all of which are the important components of PM2.5. Among the 19 environmental factors studied including air pollutants, meteorological factors, and geographical conditions, PM2.5 concentration manifested the strongest correlations with the functional genes for the transformation of ammonium and sulfate. Moreover, the PM2.5 concentration rather than the sampling site will drive the distribution of functional genera. Thus, a bi-directional relationship between PM2.5 and bacterial metabolism is suggested. Our findings shed light on the potential bacterial pathway for the biogeochemical cycling in the atmosphere and the important role of PM2.5, offering a new perspective for atmospheric ecology and pollution control.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , Atmosphere , Carbon , China , Environmental Monitoring , Nitrogen , Particulate Matter/analysis , RNA, Ribosomal, 16S/genetics , Seasons , SulfurABSTRACT
The first and limiting step of nitrification is catalyzed by ammonia-oxidizing archaea (AOA) and bacteria (AOB). Recently, complete ammonia oxidizers (comammox Nitrospira) have been discovered to perform complete nitrification in one cell, yet their role in soil nitrification is still unclear. This study investigated the abundance and contribution of aerobic ammonia oxidizers in typical soil habitats, and assessed the role of comammox Nitrospira in ammonia-oxidizing communities. The results showed that comammox Nitrospira were dominant in 70% of the samples and their abundance displayed a significant positive correlation with nitrification potential. The median amoA gene transcription level of comammox Nitrospira exceeded that of AOA and AOB in in-situ soils. The abundance of comammox Nitrospira was negatively correlated with soil pH, dominating in 84% of soil samples with pH < 6.17. The results challenge the role of AOA and AOB in soils, highlighting the importance of comammox Nitrospira in soil nitrification, especially in acid soils. This work supports better understanding and regulation of the soil nitrogen cycle.
Subject(s)
Nitrification , Soil , Ammonia , Archaea/genetics , Bacteria/genetics , Oxidation-Reduction , Phylogeny , Soil MicrobiologyABSTRACT
Background: Helicobacter pylori prevalence and gastric cancer rates are remarkably high in Peru. Effective antimicrobial regimens are essential for successful H. pylori eradication. We aimed at assessing antimicrobial resistance rates to first- and second-line therapeutic agents in H. pylori strains detected in gastric biopsy samples. Materials and Methods: Gastric biopsy samples (antrum and corpus) were collected from therapy-naive patients (n = 154). H. pylori presence in the samples was confirmed by histopathology. Genotypic resistance to clarithromycin and quinolones was determined by real-time PCR. Results: Histology results were 100% concordant with PCR results (97/154; 63% H. pylori-positive in both). In 6% (6/97) of the patients, we found discordant results of H. pylori infection in antrum and corpus samples from the same patient. Resistance rates to clarithromycin and quinolone were 34% (33/97) and 68% (56/82), respectively. Antimicrobial resistance to both antimicrobials was 30% (25/82). Conclusion: Antimicrobial resistance rates of H. pylori to clarithromycin and quinolones are very high in Lima, Peru. Many first- and second-line, empiric eradication regimens may not be recommended for Peruvian patients.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Helicobacter pylori/drug effects , Stomach/microbiology , Adult , Aged , Biopsy , DNA Gyrase/genetics , Drug Resistance, Multiple, Bacterial , Female , Genotype , Helicobacter pylori/genetics , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Peru , Real-Time Polymerase Chain ReactionABSTRACT
High amounts of deposited nitrogen (N) dramatically influence the stability and functions of alpine ecosystems by changing soil microbial community functions, but the mechanism is still unclear. To investigate the impacts of increased N deposition on microbial community functions, a 2-year multilevel N addition (0, 10, 20, 40, 80 and 160 kg N ha-1 year-1) field experiment was set up in an alpine steppe on the Tibetan Plateau. Soil microbial functional genes (GeoChip 4.6), together with soil enzyme activity, soil organic compounds and environmental variables, were used to explore the response of microbial community functions to N additions. The results showed that the N addition rate of 40 kg N ha-1 year-1 was the critical value for soil microbial functional genes in this alpine steppe. A small amount of added N (≤40 kg N ha-1 year-1) had no significant effects on the abundance of microbial functional genes, while high amounts of added N (>40 kg N ha-1 year-1) significantly increased the abundance of soil organic carbon degradation genes. Additionally, the abundance of microbial functional genes associated with NH4+, including ammonification, N fixation and assimilatory nitrate reduction pathways, was significantly increased under high N additions. Further, high N additions also increased soil organic phosphorus utilization, which was indicated by the increase in the abundance of phytase genes and alkaline phosphatase activity. Plant richness, soil NO2-/NH4+ and WSOC/WSON were significantly correlated with the abundance of microbial functional genes, which drove the changes in microbial community functions under N additions. These findings help us to predict that increased N deposition in the future may alter soil microbial functional structure, which will lead to changes in microbially-mediated biogeochemical dynamics in alpine steppes on the Tibetan Plateau and will have extraordinary impacts on microbial C, N and P cycles.
Subject(s)
Carbon , Nitrogen , Carbon/analysis , Grassland , Nitrogen/analysis , Soil , Soil Microbiology , TibetABSTRACT
Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) has reached epidemic proportions with no pharmacological therapy approved. Lower circulating glycine is consistently reported in patients with NAFLD, but the causes for reduced glycine, its role as a causative factor, and its therapeutic potential remain unclear. We performed transcriptomics in livers from humans and mice with NAFLD and found suppression of glycine biosynthetic genes, primarily alanine-glyoxylate aminotransferase 1 (AGXT1). Genetic (Agxt1 -/- mice) and dietary approaches to limit glycine availability resulted in exacerbated diet-induced hyperlipidemia and steatohepatitis, with suppressed mitochondrial/peroxisomal fatty acid ß-oxidation (FAO) and enhanced inflammation as the underlying pathways. We explored glycine-based compounds with dual lipid/glucose-lowering properties as potential therapies for NAFLD and identified a tripeptide (Gly-Gly-L-Leu, DT-109) that improved body composition and lowered circulating glucose, lipids, transaminases, proinflammatory cytokines, and steatohepatitis in mice with established NASH induced by a high-fat, cholesterol, and fructose diet. We applied metagenomics, transcriptomics, and metabolomics to explore the underlying mechanisms. The bacterial genus Clostridium sensu stricto was markedly increased in mice with NASH and decreased after DT-109 treatment. DT-109 induced hepatic FAO pathways, lowered lipotoxicity, and stimulated de novo glutathione synthesis. In turn, inflammatory infiltration and hepatic fibrosis were attenuated via suppression of NF-κB target genes and TGFß/SMAD signaling. Unlike its effects on the gut microbiome, DT-109 stimulated FAO and glutathione synthesis independent of NASH. In conclusion, impaired glycine metabolism may play a causative role in NAFLD. Glycine-based treatment attenuates experimental NAFLD by stimulating hepatic FAO and glutathione synthesis, thus warranting clinical evaluation.
Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Animals , Diet, High-Fat , Fatty Acids , Glutathione , Glycine , Humans , Liver , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapyABSTRACT
The use of tunneled dialysis catheters (TDCs) for patients in need of hemodialysis treatments (HDs) causes a significant number of bloodstream infections (BSIs), with very few viable preventative/treatment methods. Use of antibiotics is relatively ineffective due to the development of multidrug-resistant bacterial strains and the inability to penetrate bacterial biofilms. Nitric oxide (NO) is an endogenous gas molecule that has broad-spectrum antimicrobial/antibiofilm activity. In this study, the potential of creating a NO-releasing insert device that is attached onto the hub region cap of TDCs and locally releases NO within the TDC hub is evaluated for its antimicrobial/antibiofilm effectiveness. The NO-releasing insert contains the natural NO donor S-nitrosoglutathione (GSNO), along with zinc oxide (ZnO) nanoparticles to accelerate NO release from the GSNO, within a short silicone tube that is sealed at both ends and attached to the catheter cap. An in vitro 3-d-long antimicrobial study using catheter hubs yielded >6.6 log reductions of both Pseudomonas aeruginosa and Staphylococcus aureus for the NO-releasing insert device compared to controls. Two 14-d-long sheep studies demonstrated that the NO-releasing insert devices are exceptionally potent at preventing bacteria/biofilm growth on the inner lumen walls of TDCs compared to controls that have no preventative treatment devices as well as implanted TDCs that have commercially available chlorhexidine-treated insert devices placed within the hub regions.
Subject(s)
Anti-Bacterial Agents/pharmacology , Catheters, Indwelling/adverse effects , Disinfectants/pharmacology , Nitric Oxide/pharmacology , Renal Dialysis/adverse effects , Sepsis/drug therapy , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Disinfectants/chemical synthesis , Disinfectants/chemistry , Disinfection , Humans , Microbial Sensitivity Tests , Nitric Oxide/chemical synthesis , Nitric Oxide/chemistry , Pseudomonas aeruginosa/drug effects , Sepsis/microbiology , Staphylococcus aureus/drug effectsABSTRACT
Denitrifying anaerobic methane oxidizing (DAMO) bacteria are newly discovered microorganisms that use methane as the electron donor to reduce nitrite into dinitrogen. They have potential value on nitrogen removal from wastewater. However, the oxygen exposure in engineering is considered one of the bottlenecks for DAMO engineering application. In this work, we cultured DAMO bacteria under oxic and anoxic conditions in a gas-lift sequencing batch reactor (GLSBR) to explore DAMO bacterial response to oxygen stress. Under oxic conditions (7.5-8 mg O2/L), the extension of hydraulic retention time (HRT) from 2 days to 4 days increased DAMO bacterial abundance by 3.8 times. Under anoxic conditions (0.2-0.5 mg O2/L), DAMO bacterial abundance increased by 30.1 times and were kept over 2.0 × 1011 copies g-1 wet sludge. During the enrichment, microbial aggregates were formed and DAMO bacteria tended to be distributed inside the aggregates. Notably, aerobic methanotrophs existed in the whole process, capable of consuming oxygen and providing a suitable environment for DAMO bacterial growth. Finally, DAMO bacteria were enriched and the relative abundance was 16.16%. This work provides new insights into DAMO bacterial enrichment and their application in wastewater treatment.
Subject(s)
Methylococcaceae , Anaerobiosis , Bioreactors , Denitrification , Methane , Nitrites , Oxidation-Reduction , OxygenABSTRACT
As the most abundant microbes in the atmosphere, airborne bacteria are closely involved in affecting human health, regional climate and ecological balance. The mobility of airborne microorganisms makes it necessary to study the community dynamic in short cycle. Nevertheless, it remains obscure how the airborne bacteria especially the pathogenic bacteria vary on the small time scale of day and night. To investigate the nycterohemeral discrepancy of airborne total bacteria and pathogenic bacteria, PM2.5 samples were collected in Hangzhou between day and night. Microbial taxonomic information was obtained through 16S rRNA gene sequencing and "human pathogens database" screening. Further analyses based on Multiple Regression Matrices (MRM) approach and Concentration Weighted Trajectory (CWT) model were conducted to elucidate the effect of local environmental factors and long-range transport. The community composition of total bacteria tended to be similar in the daytime while pathogenic bacteria turned out to be homogeneous in the nighttime. To be vigilant, the diversity of airborne pathogenic bacteria echoed the frequency of anthropogenic activities with the pathogen inhalation rate roughly at 428 copies/h and 235 copies/h respectively in daytime and nighttime. The nycterohemeral discrepancy of total bacteria was principally driven by the filtering of environmental factors, i.e., CO and NO2, indicating that anthropogenic activities brought about the homogeneity. Airborne pathogenic bacteria coupled with the strong resistances of environmental filtering stood out from their non-pathogenic counterpart, which enabled the long-range transport. Indeed, the nycterohemeral discrepancy of pathogenic bacteria was shaped by the transport of air masses. This research filled the gaps in temporal variance of airborne microorganisms on the small time scale of day and night, providing crucial foundation for precisely predicting ecological and health effects of bioaerosols.
Subject(s)
Air Microbiology , Particulate Matter , Bacteria/genetics , Environmental Monitoring , Humans , Particulate Matter/analysis , RNA, Ribosomal, 16S/geneticsABSTRACT
Haze pollution is inseparable from the transformation of air pollutants especially the ammonium and sulfate. Chemical and physical processes play important roles in this transformation. However, the role of microbial processes has rarely been studied. In this report, we applied the cultivation-independent metagenomic approach to study airborne microorganisms, investigating the potential microbial-catalyzed transformation of ammonium and sulfate in PM2.5 samples. Functional genes predict that airborne microorganisms have the potential to catalyze ammonium formation but not ammonium oxidation since no ammoxidation genes were identified. We also found that the frequency of sulfate-forming genes was 1.56 times of those for sulfate-reducing genes. It was speculated that microbial metabolisms in the atmosphere could contribute to the accumulation of ammonium and sulfate. With the increase of PM2.5 concentration, the frequency of functional genes and the relative abundance of genera which involved in nitrogen and sulfur metabolisms increased. That suggested air pollution was conducive to the microbial-mediated formation of ammonium and sulfate. Overall, our results provided evidence for the possible role of microbial processes in the air pollutant transformation and brought a new perspective for studying the formation of secondary air pollutants.
Subject(s)
Air Pollutants/analysis , Ammonium Compounds , China , Environmental Monitoring , Particulate Matter/analysis , Seasons , Sulfates/analysisABSTRACT
Host Defense Peptides (HDPs) have gained considerable interest due to the omnipresent threat of bacterial infection as a serious public health concern. However, development of HDPs is impeded by several drawbacks, such as poor selectivity, susceptibility to proteolytic degradation, low-to-moderate activity and requiring complex syntheses. Herein we report a class of lipo-linear α/urea-γ-AApeptides with a hybrid backbone and low molecular weight. The heterogeneous backbone not only enhances chemodiversity, but also shows effective antimicrobial activity against Gram-positive bacteria and is capable of disrupting bacterial membranes and killing bacteria rapidly. Given their low molecular weight and ease of access via facile synthesis, they could be practical antibiotic agents.
Subject(s)
Amides/pharmacology , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Bacterial Infections/drug therapy , Gram-Positive Bacteria/drug effects , Lipopeptides/chemistry , Peptides/chemistry , Urea/chemistry , Amides/chemistry , Amino Acid Sequence , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Cell Membrane Permeability , Drug Evaluation, Preclinical , Gram-Negative Bacteria/drug effects , Humans , Lipopeptides/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Molecular Weight , Peptides/pharmacology , Peptidomimetics/chemistry , Peptidomimetics/pharmacology , Solid-Phase Synthesis Techniques , Structure-Activity RelationshipABSTRACT
Currently, most antimicrobial topical treatments utilize antibiotics to prevent or treat infection at a wound site. However, with the ongoing evolution of multi-drug resistant bacterial strains, there is a high demand for alternative antimicrobial treatments. Nitric oxide (NO) is an endogenous gas molecule with potent antimicrobial activity, which is effective against a wide variety of bacterial strains. In this study, the potential for creating NO releasing creams containing the naturally occurring NO carrier, S-nitrosoglutathione (GSNO), are characterized and evaluated. GSNO is shown to have prolonged stability (>300 days) when mixed and stored within Vaseline at 24⯰C. Further, enhanced proliferation of NO from GSNO using zinc oxide nanoparticles (ZnO) is demonstrated. Triggering NO release from the GSNO/Vaseline mixture using a commercial zinc oxide-containing cream exhibits first-order NO release kinetics with the highest %NO release over the first 6â¯h. Significant killing effects against S. aureus, S. epidermidis, and P. aeruginosa are demonstrated for the GSNO/Vaseline/ZnO cream mixtures in a proportional manner dependent upon the concentration of GSNO in the final mixture.
Subject(s)
Anti-Bacterial Agents/pharmacology , Nitric Oxide/metabolism , S-Nitrosoglutathione/pharmacology , Zinc Oxide/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Microbial Sensitivity Tests , Nitric Oxide/chemistry , Pseudomonas aeruginosa/drug effects , S-Nitrosoglutathione/chemistry , S-Nitrosoglutathione/metabolism , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , Zinc Oxide/chemistry , Zinc Oxide/metabolismABSTRACT
Nitric oxide (NO) releasing polymers have been widely applied as biomaterials for a variety of biomedical implants and devices. However, the chemical leaching of NO donors and their byproduct species is almost always observed during the application of polymers doped with NO donors, unless the donor is covalently linked to the polymer. Herein, we report the first NO releasing poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) fluorinated copolymer prepared by incorporating a fluorinated S-nitrosothiol as the NO donor. Under physiological conditions, the resulting polymeric films can release NO for 16â¯days. Importantly, due to both fluorine-fluorine and electrostatic charge interactions between the fluorinated NO donor and the PVDF-HFP copolymer, the total chemical leaching of the fluorinated NO donor and its disulfide product after 9â¯day was only 0.6% (mol%) of the initial amount of NO donor loaded into the film. These new NO release PVDF-HFP films exhibit antimicrobial and anti-biofilm activities against both Gram positive S. aureus and Gram negative P. aeruginosa strains. The NO-releasing PVDF-HFP polymer can also be coated on Teflon tubing to release NO under physiological conditions for extended time periods. This NO-releasing PVDF-HFP copolymer with greatly reduced chemical leaching could help enhance the biocompatibility and antimicrobial activity of various biomedical devices. STATEMENT OF SIGNIFICANCE: Fluoropolymers have been widely used in creating various biomedical implants and devices. However, nitric oxide (NO) release fluoropolymers have not been well studied to date. Additionally, in the application of biomaterials doped with NO donors, a significant amount of NO donors and their byproducts almost always leach into aqueous environment. We now report an NO releasing poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) fluoropolymer by incorporating a new fluorinated S-nitrosothiol. The NO release can last for 16â¯days under physiological conditions. The total chemical leaching was determined to be only 0.6â¯mol% of the initial S-nitrosothiol loaded. As expected, significant antimicrobial/anti-biofilm activities of the NO release PVDF-HFP film were observed against Gram positive S. aureus and Gram negative P. aeruginosa bacterial strains.
Subject(s)
Anti-Bacterial Agents/chemistry , Biofilms/growth & development , Membranes, Artificial , Nitric Oxide Donors/chemistry , Nitric Oxide/chemistry , Pseudomonas aeruginosa/physiology , Staphylococcus aureus/physiology , Vinyl Compounds/chemistryABSTRACT
The intertidal zone is an important buffer and a nitrogen sink between land and sea. Ammonia oxidation is the rate-limiting step of nitrification, conducted by ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). However, it remains a debatable issue regarding dominant ammonia oxidizers in this region, and environmental factors driving their spatiotemporal niche differentiation have yet to be identified. In this study, intertidal and subtidal zones of Zhoushan Islands were selected for seasonal sampling. Ammonia-oxidizing activity, quantitative PCR, and 454 high-throughput sequencing were performed to study the nitrification potential, abundance, and community structure of ammonia-oxidizing archaea and bacteria. AOA and AOB amoA abundance (107-108amoA gene copies/g dry weight sediment) varied spatiotemporally independently of environmental factors. AOA surpassed AOB in most samples, driven by sediment temperature, moisture, and total nitrogen. The diversity of both AOA and AOB differed spatiotemporally. The Nitrosopumilus and Nitrosospira clusters accounted for an absolutely dominant percentage of AOA (> 99%) and AOB (> 99%) respectively, indicating a negligible contribution of other clusters to ammonia oxidation. However, there was no significant correlation between nitrification potential and the abundance of AOA or AOB. Overall, the present study showed that AOA dominated over AOB spatiotemporally in the intertidal zone of Zhoushan Islands due to fluctuations in environmental factors, and the Nitrosopumilus and Nitrosospira clusters ecologically succeeded in the intertidal zone of Zhoushan Islands.
Subject(s)
Archaea/isolation & purification , Betaproteobacteria/isolation & purification , Geologic Sediments/microbiology , Ammonia/metabolism , Archaea/classification , Archaea/genetics , Archaea/metabolism , Betaproteobacteria/classification , Betaproteobacteria/genetics , Betaproteobacteria/metabolism , China , Ecosystem , Islands , Nitrification , Oxidation-Reduction , PhylogenyABSTRACT
Microorganisms are ubiquitous in the atmosphere, where they can disperse for a long distance. However, it remains poorly understood how these airborne microorganisms vary and which factors influence the microbial distribution in different anthropogenic activity regions. To explore the regional differences of bacteria and fungi in airborne particles, PM2.5 and PM10 samples were collected in the urban and rural areas of Hangzhou. The bacterial and fungal communities in the urban atmosphere was more similar to each other than those in the rural atmosphere. Analyses conducted by the concentration weighted trajectory model demonstrated that the local environment contributed more to the similarity of airborne bacteria and fungi compared with the atmospheric transport. The concentrations of local air pollutants (PM2.5, PM10, NO2, SO2 and CO) were positively correlated with the similarity of the bacterial and fungal communities. Additionally, the concentrations of these air pollutants in the urban site were about 1.5 times than those in the rural site. This implicated that anthropogenic activity, which is the essential cause of air pollutants, influenced the similarity of airborne bacteria and fungi in the urban area. This work ascertains the outdoor bacterial and fungal distribution in the urban and the rural atmosphere and provides a prospective model for studying the contributing factors of airborne bacteria and fungi.