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All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

A multifunctional sesquiterpene synthase integrates with cytochrome P450s to reinforce the terpenoid defense network in maize

Terpenoids, the largest and most structurally diverse class of plant natural products, play essential roles in maize defense and ecological interactions. In this study, we identified and functionally characterized a sesquiterpenoid-based defense pathway in maize centered on α-santalenoic acid, a pathogen-inducible sesquiterpenoid antibiotic. Using a combination of metabolite-based genome-wide association studies (mGWAS), linkage mapping, and heterologous expression assays, we identified ZmTPS9 as a multiproduct terpene synthase that primarily produces α-santalene and β-bisabolene. Sequence analysis and site-directed mutagenesis revealed that threonine at position 413 is critical for enzyme activity, with its deletion resulting in a complete loss of enzyme activity. The sesquiterpene hydrocarbons produced by ZmTPS9 are further oxidized by three cytochrome P450 monooxygenases, ZmCYP71Z16, ZmCYP71Z18, and ZmCYP71Z19, to yield antimicrobial metabolites including α-santalenoic acid, zealexin D1 (ZD1), and zealexin D2 (ZD2). Together, these findings demonstrate a convergent biosynthetic strategy in maize, where multiproduct terpene synthases and promiscuous P450s collaboratively generate a flexible and robust terpenoid defense network.

a-santalenoic acid↗
DOE OSTI2019

Genetic and structural insights into broad neutralization of hepatitis C virus by human V H 1-69 antibodies

An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene family V H 1-69. We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line–reverted versions of V H 1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of the V H 1-69 gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Elucidation of a bacterial pathway for catabolism of the β–β-linked dilignol pinoresinol

Monolignol-derived dimers containing β–β linkages are synthesized by vascular plants and can be released during lignin depolymerization. In this work, we isolated a bacterium, Novosphingobium rhizosphaerae LY, that grows with the β–β lignan (+)-pinoresinol as a sole growth substrate. Sequence analysis suggested that this strain encodes a broad range of pathways for assimilation of aromatic monomers as well as one enzyme implicated in pinoresinol catabolism but lacks other known pathways for aromatic dimer catabolism. We constructed a genome-wide barcoded transposon library and identified genes required for pinoresinol catabolism. Using feeding studies, compound isolation, targeted synthesis, and analysis of purified enzymes, we elucidated the biochemical intermediates and reaction pathway involved in pinoresinol catabolism. We demonstrated that the first enzymatic reaction is the reductive cleavage of a furan ring in (±)-pinoresinol with retention of configuration to yield lariciresinol. We additionally confirmed that the final pathway enzyme, PinU, is related to lignostilbene dioxygenases and oxidatively cleaves a diguaiacylbutadiene intermediate to yield vanillin and coniferaldehyde. Finally, based on the enzyme characterization, we demonstrated that the strain can grow with a second β–β lignan, (–)-syringaresinol, as a sole growth substrate. In combination, these results demonstrate a new biocatalytic route for transforming a widely occurring group of plant phenylpropanoid natural products.

Novosphingobium↗
DOE OSTI2024

Complete genomes of Mucilaginibacter sabulilitoris SNA2 and Mucilaginibacter sp. cycad4: microbes with the potential for plant growth promotion

Mucilaginibacter species have been isolated from various environments, often in association with plants. Here, we report the complete genomes of Mucilaginibacter sabulilitoris SNA2 and Mucilaginibacter sp. cycad4. The former is the first available for that species, and based on 16S sequence analysis, the latter strain is likely a new species.

Mucilaginibacter↗
DOE OSTI2022

Temporal variation in skin microbiota of cohabitating amphibians

Temporal changes and transmission patterns in host-associated microbial communities have important implications for host health. The diversity of amphibian skin microbial communities is associated with disease outcome in amphibians exposed to the fungal pathogen Batrachochytrium dendrobatidis (Bd). To successfully develop conservation strategies against Bd, we need a comprehensive understanding of how skin microbes are maintained and transmitted over time within populations. Here we used 16S rRNA sequence analysis to compare Epipedobates anthonyi frogs housed with one conspecific to frogs housed singly at four time points over the course of 1 year. We found that both α and β diversity of frog skin bacterial communities changed significantly over the course of the experiment. Specifically, we found that bacterial communities of cohabitating frogs became more similar over time. We also observed that some bacterial taxa were differentially abundant between frogs housed singly and frogs housed with a conspecific. These results suggest that conspecific contact may play a role in mediating amphibian skin microbial diversity and that turnover of skin microbial communities can occur across time. Our findings provide rationale for future studies exploring horizontal transmission as a potential mechanism of host-associated microbial maintenance in amphibians.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β–mediated AML progression

Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The proinflammatory cytokine interleukin-1β (IL-1β) is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that IL-1β–upregulated ASF1B (antisilencing function-1B), a histone chaperone, in AML progenitors compared with healthy progenitors. ASF1B, along with its paralogous protein ASF1A, recruits H3-H4 histones onto the replication fork during S-phase, a process regulated by Tousled-like kinase 1 and 2 (TLKs). Although ASF1s and TLKs are known to be overexpressed in multiple solid tumors and associated with poor prognosis, their functional roles in hematopoiesis and inflammation-driven leukemia remain unexplored. In this study, we identify that ASF1s and TLKs are overexpressed in multiple genetic subtypes of AML. We demonstrate that depletion of ASF1s significantly reduces leukemic cell growth in both in vitro and in vivo models using human cells. Using a murine model, we show that overexpression of ASF1B accelerates leukemia progression. Moreover, Asf1b or Tlk2 deletion delayed leukemia progression, whereas these proteins are dispensable for normal hematopoiesis. Through proteomics and phosphoproteomics analyses, we uncover that the TLK-ASF1 pathway promotes leukemogenesis by affecting the cell cycle and DNA damage pathways. Collectively, our findings identify the TLK1-ASF1 pathway as a novel mediator of inflammatory signaling and a promising therapeutic target for AML treatment across diverse genetic subtypes. Finally, selective inhibition of this pathway offers potential opportunities to intervene effectively, address intratumoral heterogeneity, and ultimately improve clinical outcomes in AML.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Antimicrobial resistance and genomic characterization of Salmonella Dublin isolates in cattle from the United States

Salmonella enterica subspecies enterica serotype Dublin is a host-adapted serotype in cattle, associated with enteritis and systemic disease. The primary clinical manifestation of Salmonella Dublin infection in cattle, especially calves, is respiratory disease. While rare in humans, it can cause severe illness, including bacteremia, with hospitalization and death. In the United States, S . Dublin has become one of the most multidrug-resistant serotypes. The objective of this study was to characterize S . Dublin isolates from sick cattle by analyzing phenotypic and genotypic antimicrobial resistance (AMR) profiles, the presence of plasmids, and phylogenetic relationships. S . Dublin isolates (n = 140) were selected from submissions to the NVSL for Salmonella serotyping (2014–2017) from 21 states. Isolates were tested for susceptibility against 14 class-representative antimicrobial drugs. Resistance profiles were determined using the ABRicate with Resfinder and NCBI databases, AMRFinder and PointFinder. Plasmids were detected using ABRicate with PlasmidFinder. Phylogeny was determined using vSNP. We found 98% of the isolates were resistant to more than 4 antimicrobials. Only 1 isolate was pan-susceptible and had no predicted AMR genes. All S . Dublin isolates were susceptible to azithromycin and meropenem. They showed 96% resistance to sulfonamides, 97% to tetracyclines, 95% to aminoglycosides and 85% to beta-lactams. The most common AMR genes were: sulf2 and tetA (98.6%), aph(6)-Id (97.9%), aph(3’’)-Ib, (97.1%), floR (94.3%), and blaCMY-2 (85.7%). All quinolone resistant isolates presented mutations in gyr A. Ten plasmid types were identified among all isolates with IncA/C2, IncX1, and IncFII(S) being the most frequent. The S . Dublin isolates show low genomic genetic diversity. This study provided antimicrobial susceptibility and genomic insight into S . Dublin clinical isolates from cattle in the U.S. Further sequence analysis integrating food and human origin S . Dublin isolates may provide valuable insight on increased virulence observed in humans.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Evaluation of co-circulating pathogens and microbiome from COVID-19 infections

Co-infections or secondary infections with SARS-CoV-2 have the potential to affect disease severity and morbidity. Additionally, the potential influence of the nasal microbiome on COVID-19 illness is not well understood. In this study, we analyzed 203 residual samples, originally submitted for SARS-CoV-2 testing, for the presence of viral, bacterial, and fungal pathogens and non-pathogens using a comprehensive microarray technology, the Lawrence Livermore Microbial Detection Array (LLMDA). Eighty-seven percent of the samples were nasopharyngeal samples, and 23% of the samples were oral, nasal and oral pharyngeal swabs. We conducted bioinformatics analyses to examine differences in microbial populations of these samples, as a proxy for the nasal and oral microbiome, from SARS-CoV-2 positive and negative specimens. We found 91% concordance with the LLMDA relative to a diagnostic RT-qPCR assay for detection of SARS-CoV-2. Sixteen percent of all the samples (32/203) revealed the presence of an opportunistic bacterial or frank viral pathogen with the potential to cause co-infections. The two most detected bacteria, Streptococcus pyogenes and Streptococcus pneumoniae , were present in both SARS-CoV-2 positive and negative samples. Human metapneumovirus was the most prevalent viral pathogen in the SARS-CoV-2 negative samples. Sequence analysis of 16S rRNA was also conducted to evaluate bacterial diversity and confirm LLMDA results.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

MAVS mediates a protective immune response in the brain to Rift Valley fever virus

Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiated robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo , Mavs -/- mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified defects in type I interferon and interferon responsive gene expression within microglia in Mavs -/- mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Depth-resolved sagebrush root metabolomics, rhizosphere microbial communities, and geochemistry at the East River Watershed

This data set consists of results from soil nutrient profile, untargeted metabolomics, mass spec imaging, and amplicon sequencing. Data for soil nutrient profile includes common cations (Ca, Mg, Na, and K etc.) extracted from 3 digesting steps – ammonia acetate (for exchangeable cations), nitric acid (for acid dissolved fraction), and hydrofluoric acid/perchloric acid (HF/HClO4) for whole soil digestion. It also includes concentration of organic carbon, inorganic nitrogen (ammonia and nitrate) and phosphorus (Bray-1 P and nitric acid extract), and total nitrogen and phosphorus. Data for untargeted metabolomics includes metabolomic profile for root exudate/tissues and soil extracts from depths at surface soil to saprolite, that were measured using gas chromatography – mass spectrometry (GC-MS), and liquid chromatography – tandem mass spectrometry (LC-MS/MS). Data for mass spec imaging includes spatial distribution of metabolites that were detected and annotated with Fourier transformation ion cyclotron resonance mass spectrometer (FTICR-MS). Data for amplicon sequencing includes the base paired 16S and ITS ribosomal RNA sequences from Miseq Illumina sequencing. All samples were collected from 2 sampling campaign October 2022 and June 2023. Collectively, these datasets enable a mechanistic evaluation of how nutrient acquisition, especially nitrogen and phosphorus, differs between shallow roots operating in soil and deep roots functioning within the fractured bedrock zone. All files are provided as comma-separated values (CSV) fies (.csv) and (GZIP) file (.gz). The compressed .gz FASTQ files can be read directly in R using the dada2 package as part of the amplicon sequence analysis workflow. This work was supported by the Watershed Function Science Focus Area at Lawrence Berkeley National Laboratory funded by the US Department of Energy, Office of Science, Biological and Environmental Research under Contract No. DE-AC02-05CH11231. This research was performed on a project award 60563 (https://dx.doi.org/10.46936/expl.proj.2022.60563/60008727) from the Environmental Molecular Sciences Laboratory, a DOE Office of Science User Facility sponsored by the Biological and Environmental Research program under Contract No. DE-AC05-76RL01830.

EARTH SCIENCE > AGRICULTURE > SOILS > CARBON↗
DOE OSTI2019

Investigating the role of innate immunity in viral encephalitis caused by Rift Valley fever virus

Rift Valley Fever Virus (RVFV) is a category A biodefense pathogen due to its potential for intentional spread by aerosols and the lack of a licensed vaccine or antiviral therapeutic. Although the brain is a major target of viral replication and tissue damage following aerosol infection, little is known about innate immune responses to RVFV in the brain. We are investigating the responses of resident innate immune cells of the brain (microglia and astrocytes) during RVFV infection, in order to identify how these cells are capable of controlling RVFV replication. Microglia mount a robust response to RVFV that is dependent upon mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. Mice genetically modified to have nonfunctional MAVS (MAVS "knock out" or KO mice) have significantly higher viral loads in the brain following intranasal infection, but surprisingly, many markers of immune activity were similarly upregulated in the brains of MAVS KO and wild type (WT, or “normal”) mice. This is in contrast to the in vitro response, where microglia and astrocytes derived from MAVS KO mice were unresponsive to RVFV infection. RNA-sequencing analysis of infected brain tissue revealed that key antiviral genes are not activated in the MAVS KO animals. These results are an important step towards understanding the molecular pathways responsible for controlling RVFV infection in the brain and lay the groundwork for the development of targeted therapies for the prevention of RVFV encephalitis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

NEAMS Workbench MOOSE Integration Update

The Nuclear Energy Advanced Modeling and Simulation (NEAMS) Workbench is a graphical user interface (GUI) that provides a common analysis environment for the accelerated use of the NEAMS toolkit. To improve design and analysis of current and future nuclear energy systems, the NEAMS Workbench provides an integrated development environment for model creation, review, execution, output review, and visualization for integrated tools. In addition to a GUI, the NEAMS Workbench provides the Workbench Analysis Sequence Processor, an open-source tool set that facilitates input-content assistance for supported domain-specific input languages and user-friendly syntaxes. These supported syntaxes enable accelerated development and deployment of enhanced user inputs and workflows. The Multiphysics Object-Oriented Simulation Environment (MOOSE) has been supported in the NEAMS Workbench since 2016 and receives continuous updates. Efforts to improve MOOSE-based tool integration in the NEAMS Workbench are ongoing. This document details the current and planned enhancements of the NEAMS Workbench and the MOOSE framework to improve integration and usability of MOOSE-based applications within the NEAMS Workbench.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2024

Linking Spatiotemporal Biological Data to Predict Harmful Algal Blooms

Cyanobacterial Harmful Algal Blooms (cHABs) have significant impacts on an affected region’s economy, ecology, and human health. The blooms can release toxins that kill fish and poison water for people and animals. The global adverse effects of cHABs are exacerbated by the consequences of climate change and increased pollution. Though the phenomena are well documented, scientists’ efforts to mitigate the damage are hampered by insufficient predictive models and incomplete granular knowledge of cHAB community structure. With a goal of leveraging bioinformatics and machine learning tools to better understand and predict cHABs, we are first exploring water sample data sets. Using nearly four thousand samples from the National Center for Biotechnology Information Sequence Read Archive (NCBI-SRA) across 16 years with latitude and longitude embedded in the metadata, we mapped the location of the samples onto a Lake Erie shape file. We combined information about location, date, and community taxa in the NCBI samples to discover factors that determine cHAB features. The data are separated into three distinct zones, with the majority pooled at the southwest end of the lake and occurring in 2017. The samples are rich in biological data; our next steps are to carry out whole genome sequence analysis and use the community profiles as part of our predictive machine learning model.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

TRACE Input Modernization

This work presents a Tom’s Obvious Minimal Language (TOML)-based representation of input for the US Nuclear Regulatory Commission’s TRAC/RELAP Advanced Computational Engine (TRACE) thermal hydraulics code. Implemented using the Workbench Analysis Sequence Processor (WASP), the approach maps traditional TRACE input structures to a hierarchical format composed of named parameters, typed values, and native data collections. The resulting representation preserves TRACE’s existing modeling capabilities while providing a modern, structured interface for model development and management. WASP further extends TOML through a file import directive that supports modular model composition and reusable input organization. In addition, WASP provides extended array data entry convenience with various data repeat and interpolation capabilities. Examples of the new TOML syntax are provided for major TRACE input categories, including hydraulic components, heat structures, control systems, and trip logic. The TOML representation establishes a foundation for improved validation, tooling, automation, and model maintainability while remaining compatible with existing TRACE workflows. To facilitate migration to the TOML-based input format, the TRACE executable now supports conversion of native TRACE input into an intermediate JSON representation. A Python utility subsequently transforms the JSON data into an equivalent TOML model. Lastly, the TRACE executable now supports execution using TOML-formatted input.

Lefebvre, Robert A. [Oak Ridge National Laboratory↗
DOE OSTI2025

RhizoGrid Indexed Sorghum Rhizosphere Multi-Omics

PerCon SFA project data dentification of spatially resolved biomarkers of drought in Sorghum bicolor rhizosphere molecular-microbe interactions using a novel root cartography "RhizoGrid" system for sampling plants under drought and control conditions across 10 equally sized root zone environments (4 quadrants each). Each quadrant was sampled and processed for 16S amplicon, metabolomics, and X-ray computed tomography (XCT). Data download includes experimental metadata and results files for 16S rRNA sequence analysis of microbial community assembly (processed data files), liquid chromatography mass spectrometry (LC-MS) metabolomics analysis of microbial community root exudates (processed data files), X-ray computed tomography (XCT) spatial gradient analysis (raw and processed data files) of microbial community composition, and related computational modeling outputs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Multiplexed Knockouts in the Model Diatom Phaeodactylum by Episomal Delivery of a Selectable Cas9

Marine diatoms are eukaryotic microalgae that play significant ecological and biogeochemical roles in oceans. They also have significant potential as organismal platforms for exploitation to address biotechnological and industrial goals. In order to address both modes of research, sophisticated molecular and genetic tools are required. We presented here new and improved methodologies for introducing CRISPRCas9 to the model diatom Phaeodactylum tricornutum cells and a streamlined protocol for genotyping mutant cell lines with previously unknown phenotypes. First, bacterialconjugation was optimized for the delivery of Cas9 by transcriptionally fusing Cas9 to a selectable marker by the 2A peptide. An episome cloning strategy using both negative and positive selection was developed to streamline CRISPR-episome assembly. Next, cell line picking and genotyping strategies, that utilize manual sequencing curation, TIDE sequencing analysis, and a T7 endonuclease assay, were developed to shorten the time required to generate mutants. Following this new experimental pipeline, both singlegene and two-gene knockout cell lines were generated at mutagenesis efficiencies of 48% and 25%, respectively. Lastly, a protocol for precise gene insertions via CRISPRCas9 targeting was developed using particle-bombardment transformation methods. Overall, the novel Cas9 episome design and improved genotyping methods presented here allow for quick and easy genotyping and isolation of Phaeodactylum mutant cell lines (less than 3 weeks) without relying on a known phenotype to screen for mutants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Detection of Candida DNA in peritoneal fluids by PCR assay optimizing the diagnosis and treatment for intra-abdominal candidiasis in high-risk ICU patients: A prospective cohort study

Background Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in critically ill patients. This study aimed to investigate whether the polymerase chain reaction (PCR) assay for detecting Candida DNA in peritoneal fluids (PF) is useful in diagnosing and management of IAC in high-risk patients in intensive care unit (ICU). Methods A prospective single-center cohort study of surgical patients at high risk for IAC was conducted in the ICU. PF was collected from the abdominal drainage tubes (within 24 h) or by percutaneous puncture. Direct PF smear microscopy, PF culture, blood culture, and serum (1–3)-β-D-glucan were performed in all patients. For Candida PCR assay, the ITS1/ITS4 primers that targeted the ITS1-5.8 s-ITS2 regions were used for PCR, and sequencing analysis was used to identify the pathogen at the species level. IAC was defined according to the 2013 European consensus criteria. Results Among 83 patients at high risk for IAC, the IAC criteria were present in 17 (20.5%). The sensitivity and specificity of the Candida PCR assay were 64.7 and 89.4%, respectively, and the area under the receiver operating characteristic curve was 0.77 (95% CI: 0.63–0.91). In this cohort, the positive predictive value and negative predictive value were 90.8% (95% CI: 80.3–96.2%) and 61.1% (95% CI: 36.1–81.7%), respectively. Diagnostic consistency was moderate (kappa 0.529, p < 0.001) according to the 2013 European consensus criteria. Conclusion Detection of Candida DNA in PF using PCR can be considered an adjunct to existing routine diagnostic tools which may optimize the diagnosis and antifungal treatment of IAC in high-risk patients in the ICU.

Xie, Min↗
DOE OSTI2024

Genomic and phenotypic characterization of multidrug-resistant Salmonella enterica serovar Reading isolates involved in a turkey-associated foodborne outbreak

Salmonella is a global bacterial foodborne pathogen associated with a variety of contaminated food products. Poultry products are a common source of Salmonella -associated foodborne illness, and an estimated 7% of human illnesses in the United States are attributed to turkey products. From November 2017 to March 2019, the Centers for Disease Control and Prevention reported a turkey-associated outbreak of multidrug-resistant (MDR; resistant to ≥3 antimicrobial classes) Salmonella enterica serovar Reading ( S . Reading) linked to 358 human infections in 42 US states and Canada. Since S . Reading was seldom linked to human illness prior to this outbreak, the current study compared genomic sequences of S . Reading isolates prior to the outbreak (pre-outbreak) to isolates identified during the outbreak period, focusing on genes that were different between the two groups but common within a group. Following whole-genome sequence analysis of five pre-outbreak and five outbreak-associated turkey/turkey product isolates of S . Reading, 37 genes located within two distinct chromosomal regions were identified only in the pre-outbreak isolates: (1) an ~5 kb region containing four protein-coding genes including uidA which encodes beta-glucuronidase, pgdA encoding peptidoglycan deacetylase, and two hypothetical proteins and (2) an ~28 kb region comprised of 32 phage-like genes and the xerC gene, which encodes tyrosine recombinase (frequently associated with phage genes). The five outbreak isolates also had a deletional event within the cirA gene, introducing a translational frame shift and premature stop codon. The cirA gene encodes a protein with dual receptor functions: a siderophore receptor for transport of dihydroxybenzoylserine as well as a colicin Ia/b receptor. Significant differences for the identified genetic variations were also detected in 75 S . Reading human isolates. Of the 41 S . Reading isolates collected before or in 2017, 81 and 90% of the isolates contained the uidA and pgdA genes, respectively, but only 24% of the isolates collected after 2017 harbored the uidA and pgdA genes. The truncation event within the cirA gene was also significantly higher in isolates collected after 2017 (74%) compared to before or in 2017 (5%). Phenotypic analysis of the S . Reading isolates for colicin and cefiderocol sensitivities (CirA) and β-methyl-D-glucuronic acid utilization (UidA and accessory proteins) supported the genomic data. Overall, a similar genome reduction pattern was generally observed in both the turkey and human isolates of S . Reading during the outbreak period, and the genetic differences were present in genes that could potentially promote pathogen dissemination due to variation in Salmonella colonization, fitness, and/or virulence.

59 BASIC BIOLOGICAL SCIENCES↗