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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Predictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosa

Antibiotic-resistant bacteria rapidly spread in clinical and natural environments and challenge our modern lifestyle. A major component of defense against antibiotics in Gram-negative bacteria is a drug permeation barrier created by active efflux across the outer membrane. We identified molecular determinants defining the propensity of small peptidomimetic molecules to avoid and inhibit efflux pumps in Pseudomonas aeruginosa, a human pathogen notorious for its antibiotic resistance. Combining experimental and computational protocols, we mapped the fate of the compounds from structure-activity relationships through their dynamic behavior in solution, permeation across both the inner and outer membranes, and interaction with MexB, the major efflux transporter of P. aeruginosa. We identified predictors of efflux avoidance and inhibition and demonstrated their power by using a library of traditional antibiotics and compound series and by generating new inhibitors of MexB. The identified predictors will enable the discovery and optimization of antibacterial agents suitable for treatment of P. aeruginosa infections.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Conjugation-based genome engineering enables rapid prototyping and bioproduction in non-model bacteria

Abstract Non-model bacteria offer unique metabolic capabilities for sustainable bioproduction, yet their limited genetic accessibility hinders systematic strain development. Here we present conjugation-based serine recombinase-assisted genome engineering (cSAGE), a broad-host-range platform that enables predictable, iterative genomic integration in transformation-resistant bacteria. cSAGE combines conjugative DNA delivery, standardized low-copy vectors, orthogonal recombinases, and modular genetic parts to support rapid pathway assembly and cross-host benchmarking. Using purple nonsulfur bacteria as a testbed, we integrate promoter engineering, multi-payload genome modification, and genome-scale metabolic modeling to empirically evaluate host-dependent pathway performance. Applying this workflow, we identify strain-specific differences in photosynthetic conversion of lignin-derived p -coumarate to the thermoplastic precursor p -vinylphenol. By enabling genome engineering and functional comparison across diverse bacteria using a single plasmid system, cSAGE provides a general framework for non-model strain prototyping and biotransformation discovery.

Guzman, Michael S. [Department of Chemical Enginee↗
DOE OSTI2020

Mycobacterium Phage Butters-Encoded Proteins Contribute to Host Defense against Viral Attack [plus supplemental information]

A diverse set of prophage-mediated mechanisms protecting bacterial hosts from infection has been recently uncovered within cluster N mycobacteriophages isolated on the host, Mycobacterium smegmatis mc 2 155. In that context, we unveil a novel defense mechanism in cluster N prophage Butters. By using bioinformatics analyses, phage plating efficiency experiments, microscopy, and immunoprecipitation assays, we show that Butters genes located in the central region of the genome play a key role in the defense against heterotypic viral attack. Our study suggests that a two-component system, articulated by interactions between protein products of genes 30 and 31, confers defense against heterotypic phage infection by PurpleHaze (cluster A/subcluster A3) or Alma (cluster A/subcluster A9) but is insufficient to confer defense against attack by the heterotypic phage Island3 (cluster I/subcluster I1). Therefore, based on heterotypic phage plating efficiencies on the Butters lysogen, additional prophage genes required for defense are implicated and further show specificity of prophage-encoded defense systems. IMPORTANCE: Many sequenced bacterial genomes, including those of pathogenic bacteria, contain prophages. Some prophages encode defense systems that protect their bacterial host against heterotypic viral attack. Understanding the mechanisms undergirding these defense systems is crucial to appreciate the scope of bacterial immunity against viral infections and will be critical for better implementation of phage therapy that would require evasion of these defenses. Furthermore, such knowledge of prophage-encoded defense mechanisms may be useful for developing novel genetic tools for engineering phage-resistant bacteria of industrial importance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The application of synthetic antibacterial minerals to combat topical infections: exploring a mouse model of MRSA infection

Abstract The development of new antibiotics has stalled, and novel strategies are needed as we enter the age of antibiotic resistance. Certain naturally occurring clays have been shown to be effective in killing antibiotic resistant bacteria. However, these natural clays are too variable to be used in clinical settings. Our study shows that synthetic antibacterial minerals exhibit potent antibacterial activity against topical MRSA infections and increase the rate of wound closure relative to controls. The antibacterial minerals maintain a redox cycle between Fe 2+ /Fe 3+ and the surfaces of pyrite minerals, which act as a semiconductor and produce reactive oxygen species (ROS), while smectite minerals act as a cation exchange reservoir. Acidic conditions are maintained throughout the application of the hydrated minerals and can mitigate the alkaline pH conditions observed in chronic non-healing wounds. These results provide evidence for the strategy of ‘iron overload’ to combat antibiotic resistant infections through the maintained release of Fe 2+ and generation of ROS via distinct geochemical reactions that can break the chronic wound damage cycle.

58 GEOSCIENCES↗
DOE OSTI2025

Gramicidin and chlorhexidine encapsulated in bicontinuous microemulsions: Antimicrobial activity performance and their impact on self‐assembly

The utility of bicontinuous microemulsions (BMEs) as carriers of the antimicrobial peptide (AMP) gramicidin D and antiseptic chlorhexidine was investigated for possible topical delivery to chronic wounds. The two water-insoluble solutes dissolved in pre-formed one-phase BMEs of Water/Polysorbate 80/Limonene/Ethanol/Glycerol and Water/Aerosol-OT (AOT)/Polysorbate 85/Isopropyl Myristate and an AOT/Polysorbate 85 Winsor-III system, achieving gramicidin and chlorhexidine concentrations of 1.0 wt% and 0.5% individually and 0.5% and 0.3% in mixtures at 22°C, respectively. Small-angle neutron scattering measurements demonstrated that both solutes decreased surfactant interfacial activity and increased interfacial fluidity for the Polysorbate 80 system. For the AOT/Polysorbate 85 systems, ellipsoidal aggregates consisting of gramicidin and likely adsorbed surfactant and oil formed, while chlorhexidine enhanced the surface activity of surfactants. According to bioassays performed on artificial skin, the incorporation of melittin, gramicidin, and chlorhexidine in general enhanced the bioactivity of Polysorbate 80 BMEs for 24 h treatment against relevant antibiotic-resistant bacteria found on skin relative to controls. Yet, BME treatments were less effective than aqueous melittin control, in contrast to well diffusion bioassays performed previously. The results reflect the strong impact of AMPs and antiseptics on BME structure and dynamics and the complexity of formulating BMEs for optimal antimicrobial activity.

antimicrobial peptides↗
DOE OSTI2021

Understanding the Photochemical Properties of Polythiophene Polyelectrolyte Soft Aggregates with Sodium Dodecyl Sulfate for Antimicrobial Activity

The threat of antibiotic-resistant bacteria is an ever-increasing problem in public health. In this report, we examine the photochemical properties with a proof-of-principle biocidal assay for a novel series of regio-regular imidazolium derivative poly-(3-hexylthiophene)/sodium dodecyl sulfate (P3HT-Im/SDS) materials from ultrafast sub-ps dynamics to μs generation of reactive oxygen species (ROS) and 30 min biocidal reactivity with Escherichia coli (E. coli). This broad series encompassing pure P3HT-Im to cationic, neutral, and anionic P3HT-Im/SDS materials are all interrogated by a variety of techniques to characterize the physical material structure, electronic structure, and antimicrobial activity. Our results show that SDS complexation with P3HT-Im results in aggregate materials with reduced ROS generation and light-induced anti-microbial activity. However, our characterization reveals that the presence of non-aggregated or lightly SDS-covered polymer segments is still capable of ROS generation. Full encapsulation of the P3HT-Im polymer completely deactivates the light killing pathway. High SDS concentrations, near and above critical micelle concentration, further deactivate all anti-microbial activity (light and dark) even though the P3HT-Im regains its electronic properties to generate ROS.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Halogenation as a tool to tune antimicrobial activity of peptoids

Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N-substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library of 36 peptoids containing fluorine, chlorine, bromine and iodine atoms, which vary by length and level of halogen substitution in position 4 of the phenyl rings. As we observed a clear correlation between halogenation of an inactive model peptoid and its increased antimicrobial activity, we designed chlorinated and brominated analogues of a known peptoid and its shorter counterpart. Short brominated analogues displayed up to 32-fold increase of the activity against S. aureus and 16- to 64-fold against E. coli and P. aeruginosa alongside reduced cytotoxicity. The biological effect of halogens seems to be linked to the relative hydrophobicity and self-assembly properties of the compounds. By small angle X-ray scattering (SAXS) we have demontrated how the self-assembled structures are dependent on the size of the halogen, degree of substitution and length of the peptoid, and correlated these features to their activity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Th IV –Desferrioxamine: characterization of a fluorescent bacterial probe

Diversifying our ability to guard against emerging pathogenic threats is essential for keeping pace with global health challenges, including those presented by drug-resistant bacteria. Some modern diagnostic and therapeutic innovations to address this challenge focus on targeting methods that exploit bacterial nutrient sequestration pathways, such as the desferrioxamine (DFO) siderophore used by Staphylococcus aureus (S. aureus) to sequester Fe III . Building on recent studies that have shown DFO to be a versatile vehicle for chemical delivery, we show proof-of-principle that the Fe III sequestration pathway can be used to deliver a potential radiotherapeutic. Our approach replaces the FeIII nutrient sequestered by H 4 DFO + with Th IV and made use of a common fluorophore, FITC, which we covalently bonded to DFO to provide a combinatorial probe for simultaneous chelation paired with imaging and spectroscopy, H 3 DFO_FITC. Combining insight provided from FITC-based imaging with characterization by NMR spectroscopy, we demonstrated that the fluorescent DFO_FITC conjugate retained the Th IV chelation properties of native H4DFO+. Fluorescence microscopy with both [Th(DFO_FITC)] and [Fe(DFO_FITC)] complexes showed similar uptake by S. aureus and increased intercellular accumulation as compared to the FITC and unchelated H 3 DFO_FITC controls. Collectively, these results demonstrate the potential for the newly developed H 3 DFO_FITC conjugate to be used as a targeting vector and bacterial imaging probe for S. aureus. The results presented within provide a framework to expand H 4 DFO + and H 3 DFO_FITC to relevant radiotherapeutics (like 227Th).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Horizontal Gene Transfer and CRISPR Targeting Drive Phage-Bacterial Host Interactions and Coevolution in “Pink Berry” Marine Microbial Aggregates

Phages, which are viruses that infect bacteria, are important components of all microbial systems, in which they drive the turnover of organic matter by lysing host cells, facilitate horizontal gene transfer (HGT), and coevolve with their bacterial hosts. Bacteria resist phage infection, which is often costly or lethal, through a diversity of mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Survey of Thirteen Novel Pseudomonas putida Bacteriophages

Bacteriophages have been widely investigated as a promising treatment of food, medical equipment, and humans colonized by antibiotic-resistant bacteria. Phages pose particular interest in combating those bacteria which form biofilms, such as the medically important human pathogen Pseudomonas aeruginosa and several plant pathogens, including P. syringae . In an undergraduate lab course, P. putida was used as the host to isolate novel anti-pseudomonal bacteriophages. Environmental samples of soil and water were collected, and purified phage isolates were obtained. After Illumina sequencing, genomes of these phages were assembled de novo and annotated. Assembled genomes were compared with known genomes in the literature and GenBank to identify taxonomic relations and to refine their functional annotations. The thirteen phages described are sipho-, myo-, and podoviruses in several families of Caudoviricetes , spanning several novel genera, with genomes ranging from 40,000 to 96,000 bp. One phage (DDSR119) is unique and is the first reported P. putida siphovirus. The remaining 12 can be clustered into four distinct groups. Six are highly related to each other and to previously described Autotranscriptaviridae phages: Waldo5, PlaquesPlease, and Laces98 all belong to the Waldovirus genus, whereas Stalingrad, Bosely, and Stamos belong to the Troedvirus genus. Zuri was previously classified as the founding member of a new genus Zurivirus within the family Schitoviridae . Ebordelon and Holyagarpour each represent different species within Zurivirus , whereas Meara is a more distantly related member of the Schitoviridae . Dolphis and Jeremy are similar enough to form a genus but have only a few distant relatives among sequenced phages and are notable for being temperate. We identified the lysis cassettes in all 13 phages, compared tail spike structures, and found auxiliary metabolic genes in several. Studies like these, which isolate and characterize infectious virions, enable the identification of novel proteins and molecular systems and also provide the raw materials for further study, evaluation, and manipulation of phage proteins and their hosts.

Pseudomonas putida↗
DOE OSTI2022

Silver Nanoparticles Functionalized Nanosilica Grown over Graphene Oxide for Enhancing Antibacterial Effect

The continuous growth of multidrug-resistant bacteria due to the overuse of antibiotics and antibacterial agents poses a threat to human health. Silver nanoparticles, silica-based materials, and graphene-based materials have become potential antibacterial candidates. In this study, we developed an effective method of enhancing the antibacterial property of graphene oxide (GO) by growing nanosilica (NS) of approximately 50 nm on the graphene oxide (GO) surface. The structures and compositions of the materials were characterized through powdered X-ray diffraction (P-XRD), transmission electron microscopy (TEM), scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS), ultraviolet–visible spectroscopy (UV–VIS), dynamic light scattering (DLS), Raman spectroscopy (RM), Fourier-transform infrared spectroscopy (FTIR), Brunauer–Emmet–Teller (BET) surface area, and pore size determination. The silver nanoparticles (AgNPs) with an average diameter of 26 nm were functionalized on the nanosilica (NS) surface. The composite contained approximately 3% of silver nanoparticles. The silver nanoparticles on nanosilica supported over graphene oxide (GO/NS/AgNPs) exhibited a 7-log reduction of Escherichia coli and a 5.2-log reduction of Bacillus subtilis within one hour of exposure. Both GO/NS and GO/NS/AgNPs exhibited substantial antimicrobial effects against E. coli and B. subtilis.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Effect of Endosymbiotic Bacteria on Fungal Resistance Toward Heavy Metals

Most studies on metal removal or tolerance by fungi or bacteria focus on single isolates, without taking into consideration that some fungi in nature may be colonized by endobacteria. To address this knowledge gap, we investigated the tolerance and removal of diverse metals with two fungal species: Linnemannia elongata containing Burkholderia-related endobacteria and Benniella erionia containing Mollicute-related endobacteria. Isogenic lines of both species were generated with antibiotic treatments to remove their respective endobacteria. Experiments involved comparing the isogenic lines and wild type fungi in relation to the minimum inhibitory concentration for the metals, the fungal ability to remove these different metals via atomic adsorption spectroscopy, and the interaction of the metals with specific functional groups of the fungi and fungi-bacteria to determine the role of the bacteria via attenuated total reflection fourier transformed infrared (ATR-FTIR). Finally, we determined the influence of different metal concentrations, associated with moderate and high fungal growth inhibition, on the presence of the endobacteria inside the fungal mycelium via quantitative real-time PCR. Results showed that the presence of the endosymbiont increased B. erionia resistance to Mn 2+ and increased the removal of Fe 2+ compared to isogenic lines. The absence of the endosymbiont in L. elongata increased the fungal resistance toward Fe 2+ and improved the removal of Fe 2+ . Furthermore, when the bacterial endosymbiont was present in L. elongata , a decrease in the fungal resistance to Ca 2+ , Fe 2+ , and Cr 6+ was noticeable. In the ATR-FTIR analysis, we determined that C-H and C = O were the major functional groups affected by the presence of Cu 2+ , Mn 2+ , and Fe 2+ for L. elongata and in the presence of Cu 2+ and Ca 2+ for B. eronia . It is noteworthy that the highest concentration of Pb 2+ led to the loss of endobacteria in both L. elongata and B. eronia , while the other metals generally increased the concentration of endosymbionts inside the fungal mycelium. From these results, we concluded that bacterial endosymbionts of fungi can play a fundamental role in fungal resistance to metals. This study provides the first step toward a greater understanding of symbiotic interactions between bacteria and fungi in relation to metal tolerance and remediation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

The effects of mixed-species root zones on the resistance of soil bacteria and fungi to long-term experimental and natural reductions in soil moisture

Mixed forest stands tend to be more resistant to drought than species-specific stands partially due to complementarity in root ecology and physiology. For this work, we asked whether complementary differences in the drought resistance of soil microbiomes might contribute to this phenomenon. We experimented on the effects of reduced soil moisture on bacterial and fungal community composition in species-specific (single species) and mixed-species root zones of Norway spruce and European beech forests in a 5-year-old throughfall-exclusion experiment and across seasonal (spring-summer-fall) and latitudinal moisture gradients. Bacteria were most responsive to changes in soil moisture, especially members of Rhizobiales, while fungi were largely unaffected, including ectomycorrhizal fungi (EMF). Community resistance was higher in spruce relative to beech root zones, corresponding with the proportions of drought-favored (more in spruce) and drought-sensitive bacterial taxa (more in beech). The spruce soil microbiome also exhibited greater resistance to seasonal changes between spring (wettest) and fall (driest). Mixed-species root zones contained a hybrid of beech- and spruce-associated microbiomes. Several bacterial populations exhibited either enhanced resistance or greater susceptibility to drought in mixed root zones. Overall, patterns in the relative abundances of soil bacteria closely tracked moisture in seasonal and latitudinal precipitation gradients and were more predictive of soil water content than other environmental variables. We conclude that complementary differences in the drought resistance of soil microbiomes can occur and the likeliest form of complementarity in mixed-root zones coincides with the enrichment of drought-tolerant bacteria associated with spruce and the sustenance of EMF by beech.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

How to Evaluate Non-Growing Cells—Current Strategies for Determining Antimicrobial Resistance of VBNC Bacteria

Thanks to the achievements in sanitation, hygiene practices, and antibiotics, we have considerably improved in our ongoing battle against pathogenic bacteria. However, with our increasing knowledge about the complex bacterial lifestyles and cycles and their plethora of defense mechanisms, it is clear that the fight is far from over. One of these resistance mechanisms that has received increasing attention is the ability to enter a dormancy state termed viable but non-culturable (VBNC). Bacteria that enter the VBNC state, either through unfavorable environmental conditions or through potentially lethal stress, lose their ability to grow on standard enrichment media, but show a drastically increased tolerance against antimicrobials including antibiotics. The inability to utilize traditional culture-based methods represents a considerable experimental hurdle to investigate their increased antimicrobial resistance and impedes the development and evaluation of effective treatments or interventions against bacteria in the VBNC state. Although experimental approaches were developed to detect and quantify VBNCs, only a few have been utilized for antimicrobial resistance screening and this review aims to provide an overview of possible methodological approaches.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Co-occurrence of antibiotic, biocide, and heavy metal resistance genes in bacteria from metal and radionuclide contaminated soils at the Savannah River Site

Contaminants such as heavy metals may contribute to the dissemination of antimicrobial resistance (AMR)by enriching resistance gene determinants via co-selection mechanisms. In the present study, a survey was performed on soils collected from four areas at the Savannah River Site (SRS), South Carolina, USA, with varying contaminant profiles: relatively pristine(Upper Three Runs), heavy metals (Ash Basins), radionuclides (Pond B) and heavy metal and radionuclides (Tim’s Branch). Using 16S rRNA gene amplicon sequencing, we explored the structure and diversity of soil bacterial communities. Sites with legacies of metal and/or radionuclide contamination displayed significantly lower bacterial diversity compared to the reference site. Metagenomic analysis indicated that multidrug and vancomycin antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) including those associated with copper, arsenic, iron, nickel and zinc were prominent in all soils including the reference site. However, significant differences were found in the relative abundance and diversity of certain ARGs and MRGs in soils with metal/radionuclide contaminated soils compared to the reference site. Co-occurrence patterns revealed significant ARG/MRG subtypes in predominant soil taxa including Acidobacteriaceae, Bradyrhizobium, Mycobacterium, Streptomyces, Verrumicrobium, Actinomadura and Solirubacterales. Overall, the study emphasizes the potential risk of human activities on the dissemination of AMR in the environment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Towards modeling phage therapy

Patients infected with life-threatening multi-drug resistant (MDR) bacteria have been treated with cocktails of bacteriophages. This is a complicated form of personalized medicine as the phages given to a patient have to be selected beforehand on the basis of their lytic capacity of the infecting bacteria. Because bacteria rapidly become resistant, the evolution of resistance to a diverse cocktail of phages is a complicated dynamical process, during which competing bacterial strains replace one another by accumulating several resistance mechanisms, each of which may involve a fitness cost. As a consequence, it is typically not known why a particular phage therapy succeeded or failed, and how one can optimize the composition of the cocktails to maximize the rate of success. To improve upon this, we extend an existing in vivo -calibrated mouse model into a novel mathematical model for the human situation, and include multiple phages infecting multiple bacterial strains, differing in their resistance to each of the phages. We adjust several parameter estimates of the bacterial model to the human situation, and use the model to describe a successful case of phage therapy involving several cocktails, each containing several phages. In the model, treatment success crucially depended on pretreatment resistance levels, and on the diversity and the timing of the cocktails. Once an appropriate cocktail is found, it is less important to further optimize the infection rates of the phages. Resistant bacterial strains expand rapidly when sensitive strains decline, and the higher the infectivity of the phages, the faster resistant strains expand. Because resistance evolves rapidly, it is best to provide a diverse set of phages right from the start of therapy, i.e., to hit hard and early, and create a high genetic barrier to bacterial resistance.

59 BASIC BIOLOGICAL SCIENCES↗