Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “pathogenicity”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

A Subunit of ESCRT-III, MoIst1, Is Involved in Fungal Development, Pathogenicity, and Autophagy in Magnaporthe oryzae

The culprit of rice blast, Magnaporthe oryzae , is a filamentous fungus that seriously affects the yield and quality of rice worldwide. MoIst1, a subunit of ESCRT-III, is involved in identified ubiquitinated proteins and transports them into the intraluminal vesicles of multivesicular bodies (MVBs) for degradation in lysosomes. Here, we identify and characterize MoIst1 in M. oryzae . Disruption of MoIst1 leads to a significant decrease in sporulation and formation of appressoria, defects in response to oxidative stress, cell wall stress, hyperosmotic stress, and reduced pathogenicity. Deletion of MoIst1 also caused the decreased Pmk1 phosphorylation levels, appressorium formation, the delayed translocation and degradation of lipid droplets and glycogen, resulting in a decreased appressorium turgor. In addition, deletion of MoIst1 leads to an abnormal autophagy. In summary, our results indicate that MoIst1 is involved in sporulation, appressorium development, plant penetration, pathogenicity, and autophagy in M. oryzae .

Sun, Lixiao↗
DOE OSTI2024

In Vitro Antimicrobial Activity of Volatile Compounds from the Lichen Pseudevernia furfuracea (L.) Zopf. Against Multidrug-Resistant Bacteria and Fish Pathogens

Lichens are symbiotic organisms with unique secondary metabolism. Various metabolites from lichens have shown antimicrobial activity. Nevertheless, very few studies have investigated the antimicrobial potential of the volatile compounds they produce. This study investigates the chemical composition and antimicrobial properties of volatile compounds from Pseudevernia furfuracea collected in two regions of Morocco. Hydrodistillation was used to obtain volatile compounds from samples collected in the High Atlas and Middle Atlas. Gas chromatography–mass spectrometry (GC-MS) analysis identified phenolic cyclic compounds as the primary constituents, with atraric acid and chloroatranol being the most abundant. Additionally, eight compounds were detected in lichens for the first time. The antimicrobial activity of these compounds was assessed using disc diffusion and broth microdilution methods. Both samples demonstrated significant antimicrobial effects against multidrug-resistant human bacteria, reference microorganisms, fish pathogens, and Candida albicans, with minimum inhibitory concentrations (MICs) ranging from 1000 µg/mL to 31.25 µg/mL. This study provides the first report on the volatile compounds from Pseudevernia furfuracea and their antimicrobial effects, particularly against fish pathogens, suggesting their potential as novel antimicrobial agents for human and veterinary use. Further research is warranted to explore these findings in more detail.

Essadki, Yasser (ORCID:0009000648460075)↗
DOE OSTI2025

Diversity in the Common Fold: Structural Insights into Class D β-Lactamases from Gram-Negative Pathogens

Class D β-lactamases (DBLs) represent a major threat to antibiotic efficacy by hydrolyzing β-lactam drugs, including last-resort carbapenems, thereby driving antimicrobial resistance in Gram-negative bacteria. The enzymes share a structurally conserved two-domain α/β architecture with seven active-site motifs and three flexible extended loops (the P-loop, Ω-loop, and newly designated B-loop) that surround the active site. While each of these loops is known to influence enzyme function, their coordinated roles have not been fully elucidated. To investigate the significance of their interplay, we compared the sequences and crystal structures of 40 DBLs from clinically relevant Gram-negative pathogens and performed molecular dynamics simulations on selected representatives. Combined structural and dynamical analyses revealed a strong correlation between B-loop architecture and carbapenemase activity in the pathogens Klebsiella and Acinetobacter, particularly regarding loop length and spatial organization. These findings emphasize the B-loop’s critical contribution, in concert with the P- and Ω-loops, in tuning active site versatility, substrate recognition, catalytic activity, and structural stability. A deeper understanding of how these motifs and loops govern DBL function may inform the development of novel antibiotics and inhibitors targeting this class of enzymes.

antibiotic resistance↗
DOE OSTI2021

A Novel Glutathione S-Transferase Gtt2 Class (VpGSTT2) Is Found in the Genome of the AHPND/EMS Vibrio parahaemolyticus Shrimp Pathogen

Glutathione S-transferases are a family of detoxifying enzymes that catalyze the conjugation of reduced glutathione (GSH) with different xenobiotic compounds using either Ser, Tyr, or Cys as a primary catalytic residue. We identified a novel GST in the genome of the shrimp pathogen V. parahaemolyticus FIM- S1708+, a bacterial strain associated with Acute Hepatopancreatic Necrosis Disease (AHPND)/Early Mortality Syndrome (EMS) in cultured shrimp. This new GST class was named Gtt2. It has an atypical catalytic mechanism in which a water molecule instead of Ser, Tyr, or Cys activates the sulfhydryl group of GSH. The biochemical properties of Gtt2 from Vibrio parahaemolyticus (VpGSTT2) were characterized using kinetic and crystallographic methods. Recombinant VpGSTT2 was enzymatically active using GSH and CDNB as substrates, with a specific activity of 5.7 units/mg. Low affinity for substrates was demonstrated using both Michaelis–Menten kinetics and isothermal titration calorimetry. The crystal structure showed a canonical two-domain structure comprising a glutathione binding G-domain and a hydrophobic ligand H domain. A water molecule was hydrogen-bonded to residues Thr9 and Ser 11, as reported for the yeast Gtt2, suggesting a primary role in the reaction. Molecular docking showed that GSH could bind at the G-site in the vicinity of Ser11. G-site mutationsT9A and S11A were analyzed. S11A retained 30% activity, while T9A/S11A showed no detectable activity. VpGSTT2 was the first bacterial Gtt2 characterized, in which residues Ser11 and Thr9 coordinated a water molecule as part of a catalytic mechanism that was characteristic of yeast GTT2. The GTT2 family has been shown to provide protection against metal toxicity; in some cases, excess heavy metals appear in shrimp ponds presenting AHPND/EMS. Further studies may address whether GTT2 in V. parahaemolyticus pathogenic strains may provide a competitive advantage as a novel detoxification mechanism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Pathogenic and Apathogenic Strains of Lymphocytic Choriomeningitis Virus Have Distinct Entry and Innate Immune Activation Pathways

Lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV) share many genetic and biological features including subtle differences between pathogenic and apathogenic strains. Despite remarkable genetic similarity, the viscerotropic WE strain of LCMV causes a fatal LASV fever-like hepatitis in non-human primates (NHPs) while the mouse-adapted Armstrong (ARM) strain of LCMV is deeply attenuated in NHPs and can vaccinate against LCMV-WE challenge. Here, we demonstrate that internalization of WE is more sensitive to the depletion of membrane cholesterol than ARM infection while ARM infection is more reliant on endosomal acidification. LCMV-ARM induces robust NF-κB and interferon response factor (IRF) activation while LCMV-WE seems to avoid early innate sensing and failed to induce strong NF-κB and IRF responses in dual-reporter monocyte and epithelial cells. Toll-like receptor 2 (TLR-2) signaling appears to play a critical role in NF-κB activation and the silencing of TLR-2 shuts down IL-6 production in ARM but not in WE-infected cells. Pathogenic LCMV-WE infection is poorly recognized in early endosomes and failed to induce TLR-2/Mal-dependent pro-inflammatory cytokines. Following infection, Interleukin-1 receptor-associated kinase 1 (IRAK-1) expression is diminished in LCMV-ARM- but not LCMV-WE-infected cells, which indicates it is likely involved in the LCMV-ARM NF-κB activation. By confocal microscopy, ARM and WE strains have similar intracellular trafficking although LCMV-ARM infection appears to coincide with greater co-localization of early endosome marker EEA1 with TLR-2. Both strains co-localize with Rab-7, a late endosome marker, but the interaction with LCMV-WE seems to be more prolonged. These findings suggest that LCMV-ARM’s intracellular trafficking pathway may facilitate interaction with innate immune sensors, which promotes the induction of effective innate and adaptive immune responses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host–pathogen conflict

DNA viruses in the family Poxviridae encode poxin enzymes that degrade the immune second messenger 2'3'-cGAMP to inhibit cGAS-STING immunity in mammalian cells. The closest homologs of poxin exist in the genomes of insect viruses suggesting a key mechanism of cGAS-STING evasion may have evolved outside of mammalian biology. Here we use a biochemical and structural approach to discover a broad family of 369 poxins encoded in diverse viral and animal genomes and define a prominent role for 2'3'-cGAMP cleavage in metazoan host-pathogen conflict. Structures of insect poxins reveal unexpected homology to flavivirus proteases and enable identification of functional self-cleaving poxins in RNA-virus polyproteins. Our data suggest widespread 2'3'-cGAMP signaling in insect antiviral immunity and explain how a family of cGAS-STING evasion enzymes evolved from viral proteases through gain of secondary nuclease activity. Poxin acquisition by poxviruses demonstrates the importance of environmental connections in shaping evolution of mammalian pathogens.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1990

Survival of pathogenic bacteria under nutrient starvation conditions

The survival of opportunistic pathogenic microorganisms in water, under nutrient-limiting conditions, has been investigated in order to ascertain whether human pathogens can survive within a water-distribution system of the kind proposed for the NASA Space Station. Cultures of a strain of pseudomonas aeruginosa and two strains of staphylococcus aureus were incubated at 10, 25, or 37 C, and samples at 1 day, 1 week, 1 month, and six weeks. While neither of the staphylococcus strains tested were detected after 1 week of starvation, the pseudomonas strain can survive in deionized water at all three temperatures.

Boyle, Michael↗
NASA NTRS1993

Bloodborne Pathogens Program

The final rule on the Occupational Exposure to Bloodborne Pathogens was published in the Federal Register on Dec. 6, 1991. This Standard, 29 CFR Part 1910.130, is expected to prevent 8,900 hepatitis B infections and nearly 200 deaths a year in healthcare workers in the U.S. The Occupational Medicine and Environmental Health Services at KSC has been planning to implement this standard for several years. Various aspects of this standard and its Bloodborne Pathogens Program at KSC are discussed.

Blasdell, Sharon↗
NASA NTRS1993

OSHA Bloodborne Pathogens Standards Exposure Control Plan

The Hummer Associates Exposure Control Plan is designed to reduce significant occupational exposure to bloodborne pathogens and infectious materials for Hummer Associates health care personnel. Under universal precautions, all patients and all body fluids are considered potentially infectious for bloodborne pathogens. Medical personnel need not be at increased risk if universal precautions are correctly understood and followed. This program covers all employees who could reasonably anticipate contact with blood or other potentially infectious materials during the performance of their job responsibilities. Although HIV and hepatitis B are mentioned most often, this program applies to all bloodborne diseases. The two main components needed to implement this program are universal precautions and engineering/work practice controls. This program covers all employees who may have occupational exposure to blood or other potentially infectious materials. Other aspects of this program are discussed.

Luhrs, Caro Elise↗
NASA NTRS2001

Growth in microgravity increases susceptibility of soybean to a fungal pathogen

The influence of microgravity on the susceptibility of soybean roots to Phytophthora sojae was studied during the Space Shuttle Mission STS-87. Seedlings of soybean cultivar Williams 82 grown in spaceflight or at unit gravity were untreated or inoculated with the soybean root rot pathogen P. sojae. At 3, 6 and 7 d after launch while still in microgravity, seedlings were photographed and then fixed for subsequent microscopic analysis. Post-landing analysis of the seedlings revealed that at harvest day 7 the length of untreated roots did not differ between flight and ground samples. However, the flight-grown roots infected with P. sojae showed more disease symptoms (percentage of brown and macerated areas) and the root tissues were more extensively colonized relative to the ground controls exposed to the fungus. Ethylene levels were higher in spaceflight when compared to ground samples. These data suggest that soybean seedlings grown in microgravity are more susceptible to colonization by a fungal pathogen relative to ground controls.

manned↗
NASA NTRS2004

Evidence of pathogenic microbes in the International Space Station drinking water: reason for concern?

Molecular analyses were carried out on four preflight and six postflight International Space Station (ISS)-associated potable water samples at various stages of purification, storage, and transport, to ascertain their associated microbial diversities and overall microbial burdens. Following DNA extraction, PCR amplification, and molecular cloning procedures, rDNA sequences closely related to pathogenic species of Acidovorax, Afipia, Brevundimonas, Propionibacterium, Serratia, and others were recovered in varying abundance. Retrieval of sequences arising from the iodine (biocide)-reducing Delftia acidovorans in postflight waters is also of concern. Total microbial burdens of ISS potable waters were derived from data generated by an ATP-based enumeration procedure, with results ranging from 0 to 4.9 x 10(4) cells/ml. Regardless of innate biases in sample collection and analysis, such circumstantial evidence for the presence of viable, intact pathogenic cells should not be taken lightly. Implementation of new cultivation approaches and/or viability-based assays are requisite to confirm such an occurrence.

STS-113 Shuttle Project↗
NASA NTRS2006

Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection.

Nickerson, Cheryl A.↗
NASA NTRS2016

Spaceflight and Simulated Microgravity Increases Virulence of the Known Bacterial Pathogen S. Marcescens

After spaceflight, the number of immune cells is reduced in humans. In other research models, including Drosophila, not only is there a reduction in the number of plasmatocytes, but expression of immune-related genes is also changed after spaceflight. These observations suggest that the immune system is compromised after exposure to microgravity. It has also been reported that there is a change in virulence of some bacterial pathogens after spaceflight. We recently observed that samples of gram-negative S. marcescens retrieved from spaceflight is more virulent than ground controls, as determined by reduced survival and increased bacterial growth in the host. We were able to repeat this finding of increased virulence after exposure to simulated microgravity using the rotating wall vessel, a ground based analog to microgravity. With the ground and spaceflight samples, we looked at involvement of the Toll and Imd pathways in the Drosophila host in fighting infection by ground and spaceflight samples. We observed that Imd-pathway mutants were more susceptible to infection by the ground bacterial samples, which aligns with the known role of this pathway in fighting infections by gram-negative bacteria. When the Imd-pathway mutants were infected with the spaceflight sample, however, they exhibited the same susceptibility as seen with the ground control bacteria. Interestingly, all mutant flies show the same susceptibility to the spaceflight bacterial sample as do wild type flies. This suggests that neither humoral immunity pathway is effectively able to counter the increased pathogenicity of the space-flown S. marcescens bacteria.

immunity↗
NASA NTRS2016

Draft Genome Sequences of Biosafety Level 2 Opportunistic Pathogens Isolated From the Environmental Surfaces of the International Space Station

The draft genome sequences of 20 biosafety level 2 (BSL-2) opportunistic pathogens isolated from the environmental surfaces of the International Space Station (ISS) were presented. These genomic sequences will help in understanding the influence of microgravity on the pathogenicity and virulence of these strains when compared with Earth strains.

Aleksandra Checinska Sielaff↗
DOE OSTI2020

Functionalized surfaces for the destruction of pathogens and organics

The disclosure is directed to a surface having a binding component applied thereto for the adsorption or capture of pathogens and organic molecules or materials. The surface may be a component of a porous or nonporous substrate. The binding component may also bind a photocatalyst to the surface for photocatalytic destruction of the captured pathogens and organic molecules or materials.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Granulibacter bethesdensis, a Pathogen from Patients with Chronic Granulomatous Disease, Produces a Penta-Acylated Hypostimulatory Glycero-D-talo-oct-2-ulosonic Acid–Lipid A Glycolipid (Ko-Lipid A)

Granulibacter bethesdensis can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact G. bethesdensis (Gb) is hypostimulatory compared to Escherichia coli, i.e., cytokine production in human blood requires 10–100 times more G. bethesdensis CFU/mL than E. coli. To better understand the pathogenicity of G. bethesdensis, we isolated its lipopolysaccharide (GbLPS) and characterized its lipid A. Unlike with typical Enterobacteriaceae, the release of presumptive Gb lipid A from its LPS required a strong acid. NMR and mass spectrometry demonstrated that the carbohydrate portion of the isolated glycolipid consists of α-Manp-(1→4)-β-GlcpN3N-(1→6)-α-GlcpN-(1⇿1)-α-GlcpA tetra-saccharide substituted with five acyl chains: the amide-linked N-3′ 14:0(3-OH), N-2′ 16:0(3-O16:0), and N-2 18:0(3-OH) and the ester-linked O-3 14:0(3-OH) and 16:0. The identification of glycero-d-talo-oct-2-ulosonic acid (Ko) as the first constituent of the core region of the LPS that is covalently attached to GlcpN3N of the lipid backbone may account for the acid resistance of GbLPS. In addition, the presence of Ko and only five acyl chains may explain the >10-fold lower proinflammatory potency of GbKo–lipidA compared to E. coli lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the G.bethesdensis Ko–lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

A Case Study on Pathogen Transport, Deposition, Evaporation and Transmission: Linking High-Fidelity Computational Fluid Dynamics Simulations to Probability of Infection

A high-fidelity, low-Mach computational fluid dynamics simulation tool that includes evaporating droplets and variable-density turbulent flow coupling is well-suited to ascertain transmission probability and supports risk mitigation methods development for airborne infectious diseases such as COVID-19. A multi-physics large-eddy simulation-based paradigm is used to explore droplet and aerosol pathogen transport from a synthetic cough emanating from a kneeling humanoid. For an outdoor configuration that mimics the recent open-space social distance strategy of San Francisco, maximum primary droplet deposition distances are shown to approach 8.1 m in a moderate wind configuration with the aerosol plume transported in excess of 15 m. In quiescent conditions, the aerosol plume extends to approximately 4 m before the emanating pulsed jet becomes neutrally buoyant. A dose–response model, which is based on previous SARS coronavirus (SARS-CoV) data, is exercised on the high-fidelity aerosol transport database to establish relative risk at eighteen virtual receptor probe locations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina

The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host–pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype–phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.

59 BASIC BIOLOGICAL SCIENCES↗