Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Antimicrobial”

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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1997

Development of an Antimicrobial Susceptibility Testing Method Suitable for Performing During Space Flight

Very little is known regarding the affects of the microgravity environment of space flight upon the action of antimicrobial agents on bacterial pathogens. This study was undertaken to develop a simple method for conducting antibacterial susceptibility tests during a Space Shuttle mission. Specially prepared susceptibility test research cards (bioMerieux Vitek, Hazelwood, MO) were designed to include 6-11 serial two-fold dilutions of 14 antimicrobial agents, including penicillins, cephalosporins, a Beta-lactamase inhibitor, vancomycin, erythromycin, tetracycline, gentamicin, ciprofloxacin, and trimethoprim/sulfamethoxazole. Minimal inhibitory concentrations (MICS) of the drugs were determined by visual reading of color endpoints in the Vitek research cards made possible by incorporation of a colorimetric growth indicator (alamarBlue(Trademark), Accumed International, Westlake, OH). This study has demonstrated reproducible susceptibility results when testing isolates of Staphylococcus aurezis, Group A Streptococcus, Enterococcusfaecalis, Escherichia coli (beta-lactamase positive and negative strains), Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomoiias aeruginosa. In some instances, the MICs were comparable to those determined using a standard broth microdilution method, while in some cases the unique test media and format yielded slightly different values, that were themselves reproducible. The proposed in-flight experiment will include inoculation of the Vitek cards on the ground prior to launch of the Space Shuttle, storage of inoculated cards at refrigeration temperature aboard the Space Shuttle until experiment initiation, then incubation of the cards for 18-48 h prior to visual interpretation of MICs by the mission's astronauts. Ground-based studies have shown reproducible MICs following storage of inoculated cards for 7 days at 4-8 C to accommodate the mission's time schedule and the astronauts' activities. For comparison, ground-based control (normal gravity) MIC values will be generated by simultaneous inoculation and incubation of a second set of test cards in a laboratory at the launch site. This procedure can provide a safe and compact experiment that should yield new information on the affects of microgravity on the biological activities of various classes of antibiotics.

Jorgensen, James H.↗
NASA NTRS2014

Condensing Heat Exchanger with Hydrophilic Antimicrobial Coating

A multi-layer antimicrobial hydrophilic coating is applied to a substrate of anodized aluminum, although other materials may form the substrate. A silver layer is sputtered onto a thoroughly clean anodized surface of the aluminum to about 400 nm thickness. A layer of crosslinked, silicon-based macromolecular structure about 10 nm thickness overlies the silver layer, and the outermost surface of the layer of crosslinked, silicon-based macromolecular structure is hydroxide terminated to produce a hydrophilic surface with a water drop contact angle of less than 10.degree.. The coated substrate may be one of multiple fins in a condensing heat exchanger for use in the microgravity of space, which has narrow channels defined between angled fins such that the surface tension of condensed water moves water by capillary flow to a central location where it is pumped to storage. The antimicrobial coating prevents obstruction of the capillary passages.

Thomas, Christopher M.↗
DOE OSTI2022

Histidine-Mediated Ion Specific Effects Enable Salt Tolerance of a Pore-Forming Marine Antimicrobial Peptide

Antimicrobial peptides (AMPs) preferentially permeate prokaryotic membranes via electrostatic binding and membrane remodeling. Such action is drastically suppressed by high salt due to increased electrostatic screening, thus it is puzzling how marine AMPs can possibly work. We examine as a model system, piscidin-1, a histidine-rich marine AMP, and show that ion-histidine interactions play unanticipated roles in membrane remodeling at high salt: Histidines can simultaneously hydrogen-bond to a phosphate and coordinate with an alkali metal ion to neutralize phosphate charge, thereby facilitating multidentate bonds to lipid headgroups in order to generate saddle-splay curvature, a prerequisite to pore formation. A comparison among Na + , K + , and Cs + indicates that histidine-mediated salt tolerance is ion specific. Here we conclude that histidine plays a unique role in enabling protein/peptide-membrane interactions that occur in marine or other high-salt environment.

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

π‐Extended Donor–Acceptor Porphyrins and Metalloporphyrins for Antimicrobial Photodynamic Inactivation

Abstract Free base, zinc and palladium π‐extended porphyrins containing fused naphthalenediamide units were employed as photosensitizers in antimicrobial photodynamic therapy (aPDT). Their efficacy, assessed by photophysical and in vitro photobiological studies on Gram‐positive bacteria, was found to depend on metal coordination, showing a dramatic enhancement of photosensitizing activity for the palladium complex.

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

A global metagenomic map of urban microbiomes and antimicrobial resistance

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Rational design of antimicrobial peptides targeting Gram-negative bacteria

Membrane-targeting host antimicrobial peptides (AMPs) can kill or inhibit the growth of Gram-negative bacteria. However, the evolution of resistance among microbes poses a substantial barrier to the long-term utility of the host AMPs. Combining experiment and molecular dynamics simulations, we demonstrate that terminal carboxyl capping enhances both membrane insertion and antibacterial activity of an AMP called P1. Furthermore, we show that a bacterial strain with evolved resistance to this peptide becomes susceptible to P1 variants with either backbone capping or lysine-to-arginine substitutions. Our results suggest that cocktails of closely related AMPs may be useful in overcoming evolved resistance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Antimicrobial Peptides Can Facilitate Whole Blood Safety from Bacteria: A Proof of Concept

With continuous improvements to blood donor deferrals and the availability of sensitive tests for donation screening for infectious agents, bacterial contamination of whole blood (WB) and blood components stored for transfusion is a rare event. Nonetheless, it still occurs and remains a transfusion-associated risk in terms of septic transfusion reactions (STRs) and transfusion-transmitted bacterial infections with morbidity and mortality outcomes. One of the risk mitigation strategies for bacterial contamination is to implement treatment with currently available proactive pathogen reduction technologies (PRTs) for these transfusion products. Here, as a proof of concept, we tested two recently developed unique cationic antimicrobial peptides (AMPs; D-CONGA and D-CONGA-Q7) for WB safety from bacterial contamination. In this study, WB was inoculated with Escherichia coli and Staphylococcus epidermidis and treated with the two peptides to evaluate their bactericidal efficacy. The results demonstrated that D-CONGA and D-CONGA-Q7 exhibit potent inhibitory activity against the bacteria with a minimal inhibitory concentration (MIC) range of 4–8 and 1–8 μM, respectively, depending on the bacterial species tested. Time-kill kinetics further confirmed that the peptides exhibit bactericidal efficacy at 8 μM by achieving a 5-log 10 reduction (99.999%) of the bacterial load in WB with a time-dependent killing profile. Furthermore, even at 20 μM, the AMPs did not negatively impact hemolysis or hemostatic properties. We have further demonstrated using a cationic exchange resin that the cationic AMPs can be separated and removed from WB after the peptide treatments. During 35-day WB storage at 2–8 °C, 4 μM D-CONGA-Q7 one-time treatment prevented S. epidermidis growth and preserved WB quality and integrity. Overall, the results described here provide the first proof of concept that certain AMPs, such as D-CONGA and D-CONGA-Q7, can facilitate WB safety from bacteria during storage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Aeromonas in South Asia: genomic insights into an environmental pathogen and reservoir of antimicrobial resistance

Aeromonads are an ecologically versatile group of bacteria that cause infections in aquatic animals and are recognised as emerging human pathogens. Despite this, our understanding of Aeromonas diversity, especially the relationship between clinical and environmental strains, remains limited. Here, we present a genomic analysis of the Aeromonas genus, comprising 1853 genomes, and a detailed comparison of clinical and environmental strains from South Asia, including 996 newly sequenced genomes from Bangladesh and India. Phylogenetic analyses revealed that Aeromonas is a highly diverse genus, with no distinct clade separating clinical and environmental isolates. We identified 28 Aeromonas species and 905 novel sequence types, comprising 72.5% of the genomes. Notably, we show a high incidence of antimicrobial resistance (AMR) genes across all isolates, including against front and last-line antibiotics. Finally, we highlight frequent misidentification of Aeromonas as Vibrio cholerae, which is relevant to cholera-endemic regions where both genera co-exist and are associated with diarrhoeal disease. Our study underscores Aeromonas as an important environmental AMR reservoir and emerging multi-species pathogen capable of spilling over into human populations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Parabacteroides distasonis : intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health

Parabacteroides distasonis is the type strain for the genus Parabacteroides, a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as Bacteroides distasonis, the strain was re-classified to form the new genus Parabacteroides in 2006. Currently, the genus consists of 15 species, 10 of which are listed as 'validly named' (P. acidifaciens, P. chartae, P. chinchillae, P. chongii, P. distasonis, P. faecis, P. goldsteinii, P. gordonii, P. johnsonii, and P. merdae) and 5 'not validly named' (P. bouchesdurhonensis, P. massiliensis, P. pacaensis, P. provencensis, and P. timonensis) by the List of Prokaryotic names with Standing in Nomenclature. The Parabacteroides genus has been associated with reports of both beneficial and pathogenic effects in human health. Herein, we review the literature on the history, ecology, diseases, antimicrobial resistance, and genetics of this bacterium, illustrating the effects of P. distasonis on human and animal health.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Ghrelin Modulates Differential Expression of Genes Relevant to Immune Activities and Antimicrobial Peptides in Primary Head Kidney Cells of Rainbow Trout ( Oncorhynchus mykiss )

Ghrelin is a peptide hormone/cytokine that regulates metabolic processes and plays essential roles in the immune system. To evaluate the immunomodulatory actions of ghrelin isoforms in rainbow trout (RT), an in vitro model was utilized with primary cells isolated from fish head kidney (HKD). These RT-HKD cells were treated with synthetic rainbow trout ghrelin and its truncated isoform, desVRQ-ghrelin, over time (0, 2, 4, and 24 h). Reverse transcriptase-coupled qPCR was used to measure the differential expression patterns of genes relevant to various immune processes and genes of antimicrobial peptides. Ghrelin isoform treatments resulted in functional perturbations that displayed overlapping and divergent patterns of gene expression. The differing actions between the two ghrelin isoforms on various assessed genes, and at differing time points, suggested that the two analogs may activate unique pathways, thereby eliciting distinct responses in fish immunity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Histidine‐Mediated Ion Specific Effects Enable Salt Tolerance of a Pore‐Forming Marine Antimicrobial Peptide

Abstract Antimicrobial peptides (AMPs) preferentially permeate prokaryotic membranes via electrostatic binding and membrane remodeling. Such action is drastically suppressed by high salt due to increased electrostatic screening, thus it is puzzling how marine AMPs can possibly work. We examine as a model system, piscidin‐1, a histidine‐rich marine AMP, and show that ion‐histidine interactions play unanticipated roles in membrane remodeling at high salt: Histidines can simultaneously hydrogen‐bond to a phosphate and coordinate with an alkali metal ion to neutralize phosphate charge, thereby facilitating multidentate bonds to lipid headgroups in order to generate saddle‐splay curvature, a prerequisite to pore formation. A comparison among Na + , K + , and Cs + indicates that histidine‐mediated salt tolerance is ion specific. We conclude that histidine plays a unique role in enabling protein/peptide‐membrane interactions that occur in marine or other high‐salt environment.

Xian, Wujing↗
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 OSTI2024

Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects

Abstract Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough—all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs’ C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence.

Huang, Weiping (ORCID:0000000273063550)↗
DOE OSTI2025

X-ray fluorescence standing wave study of the interaction of the antimicrobial peptide indolicidin with a supported model membrane

Indolicidin, a cationic antimicrobial peptide, interacts with lipid bilayers through electrostatic and hydrophobic interactions, disrupting microbial membranes. We investigated the depth-dependent localization of gold-nanoparticle-labeled indolicidin in a supported model membrane using X-ray fluorescence standing wave (SWXF) analysis. Liposomes composed of DMPC and DMPG were incubated with indolicidin labeled at its C-terminus with a 1.8 nm gold nanoparticle, then deposited onto a Si/Mo multilayer substrate via vesicle bursting. SWXF measurements revealed that at low peptide incubation concentrations (2–5 μM), gold-nanoparticle-labeled indolicidin remains primarily associated with the bilayer's outer leaflet. At higher concentrations (10 μM), the peptide penetrates deeper into the bilayer, with the labeled C-terminal region either localizing near the membrane's hydrophobic core or inducing membrane breakup. In conclusion, these findings suggest a concentration-dependent insertion mechanism.

Basnet, Gobind [Northern Illinois Univ., DeKalb, I↗
DOE OSTI2022

Antimicrobial resistance of enteric pathogens in the Military Health System, 2009 – 2019

Abstract Background Acute diarrhea (AD) can have significant impacts on military troop readiness. Medical providers must understand current trends of enteropathogen antimicrobial resistance (AMR) in service members (SMs) to inform proper, timely treatment options. However, little is known of enteric pathogen profiles across the Military Health System (MHS). The primary objectives of this study were to identify gaps in enteric pathogen surveillance within the MHS, describe the epidemiology of AMR in enteric pathogens, and identify trends across the MHS both within the Continental United States (CONUS) and outside of the Continental United States (OCONUS). Methods Health Level 7 (HL7)-formatted laboratory data were queried for all specimens where Salmonella , Shigella , and Campylobacter species, as well as Shiga toxin-producing Escherichia coli ( E. coli ) (STEC) were isolated and certified between 1 January 2009 - 31 December 2019. Antibiotic susceptibility testing (AST) results were queried and summarized where available. Descriptive statistics were calculated for each organism by specimen source, year, and susceptibility testing availability. Results Among a total of 13,852 enteric bacterial isolates, 11,877 (86%) were submitted from CONUS locations. Out of 1479 Shigella spp. and 6755 Salmonella spp. isolates, 1221 (83%) and 5019 (74%), respectively, reported any susceptibility results through the MHS. Overall, only 15% of STEC and 4% of Campylobacter spp. specimens had AST results available. Comparing AST reporting at CONUS versus OCONUS locations, AST was reported for 1175 (83%) and 46 (78%) of Shigella isolates at CONUS and OCONUS locations, respectively, and for 4591 (76%) and 428 (63%) of Salmonella isolates at CONUS and OCONUS locations, respectively. Conclusions This study revealed inconsistent enteropathogen AST conducted across the MHS, with differing trends between CONUS and OCONUS locations. Additional work is needed to assess pathogen-specific gaps in testing and reporting to develop optimal surveillance that supports the health of the force.

Ashbaugh, Hayley↗
DOE OSTI2023

An accurate and interpretable model for antimicrobial resistance in pathogenic Escherichia coli from livestock and companion animal species

Understanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causing Escherichia coli isolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F 1 score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.

Chung, Henri C.↗