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At least 1,153 records · Page 64
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility in Mycobacterium marinum

ABSTRACT Isoprenoids are a diverse class of natural products that are essential in all domains of life. Most bacteria synthesize isoprenoids through either the methylerythritol phosphate (MEP) pathway or the mevalonate (MEV) pathway, while a small subset encodes both pathways, including the pathogen Mycobacterium marinum (Mm). It is unclear whether the MEV pathway is functional in Mm, or why Mm encodes seemingly redundant metabolic pathways. Here, we show that the MEP pathway is essential in Mm, while the MEV pathway is dispensable in culture, with the ΔMEV mutant having no growth defect in axenic culture but a competitive growth defect compared to WT Mm. We found that the MEV pathway does not play a role in ex vivo or in vivo acute infection but does play a role in survival of peroxide stress. Metabolite profiling revealed that modulation of the MEV pathway causes compensatory changes in the concentration of MEP intermediates DOXP and CDP-ME, suggesting that the MEV pathway is functional and that the pathways interact at the metabolic level. Finally, the MEV pathway is upregulated early in the shift down to hypoxia, suggesting that it may provide metabolic flexibility to this bacterium. Interestingly, we found that our complemented strains, which vary in copy number of the polyprenyl synthetase idsB2 , responded differently to peroxide and UV stresses, suggesting a role for this gene as a determinant of downstream prenyl phosphate metabolism. Together, these findings suggest that MEV may serve as an anaplerotic pathway to make isoprenoids under stress conditions. IMPORTANCE Organisms from all domains of life utilize isoprenoids to carry out thousands of critical and auxiliary cellular processes, including signaling, maintaining membrane integrity, stress response, and host-pathogen interactions. The common precursor of all isoprenoids is synthesized via one of two biosynthetic pathways. Importantly, some bacteria encode both pathways, including M. marinum . We found that only one pathway is essential in M. marinum , while the nonessential pathway may confer metabolic flexibility to help the bacterium better adapt to various environmental conditions. We also found that the polyprenyl synthetase IdsB2 plays an important role in driving such phenotypes. Further, we demonstrate metabolic interplay between both functional pathways. These insights represent the first characterization of isoprenoid biosynthesis in dual pathway-encoding mycobacteria.

Qabar, Christine M. [Department of Plant and Micro↗
DOE OSTI2017

RNA-Dependent Cysteine Biosynthesis in Bacteria and Archaea

ABSTRACT The diversity of the genetic code systems used by microbes on earth is yet to be elucidated. It is known that certain methanogenic archaea employ an alternative system for cysteine (Cys) biosynthesis and encoding; tRNA Cys is first acylated with phosphoserine (Sep) by O -phosphoseryl-tRNA synthetase (SepRS) and then converted to Cys-tRNA Cys by Sep-tRNA:Cys-tRNA synthase (SepCysS). In this study, we searched all genomic and metagenomic protein sequence data in the Integrated Microbial Genomes (IMG) system and at the NCBI to reveal new clades of SepRS and SepCysS proteins belonging to diverse archaea in the four major groups (DPANN, Euryarchaeota , TACK, and Asgard) and two groups of bacteria (“ Candidatus Parcubacteria” and Chloroflexi ). Bacterial SepRS and SepCysS charged bacterial tRNA Cys species with cysteine in vitro . Homologs of SepCysE, a scaffold protein facilitating SepRS⋅SepCysS complex assembly in Euryarchaeota class I methanogens, are found in a few groups of TACK and Asgard archaea, whereas the C-terminally truncated homologs exist fused or genetically coupled with diverse SepCysS species. Investigation of the selenocysteine (Sec)- and pyrrolysine (Pyl)-utilizing traits in SepRS-utilizing archaea and bacteria revealed that the archaea carrying full-length SepCysE employ Sec and that SepRS is often found in Pyl-utilizing archaea and Chloroflexi bacteria. We discuss possible contributions of the SepRS-SepCysS system for sulfur assimilation, methanogenesis, and other metabolic processes requiring large amounts of iron-sulfur enzymes or Pyl-containing enzymes. IMPORTANCE Comprehensive analyses of all genomic and metagenomic protein sequence data in public databases revealed the distribution and evolution of an alternative cysteine-encoding system in diverse archaea and bacteria. The finding that the SepRS-SepCysS-SepCysE- and the selenocysteine-encoding systems are shared by the Euryarchaeota class I methanogens, the Crenarchaeota AK8/W8A-19 group, and an Asgard archaeon suggests that ancient archaea may have used both systems. In contrast, bacteria may have obtained the SepRS-SepCysS system from archaea. The SepRS-SepCysS system sometimes coexists with a pyrrolysine-encoding system in both archaea and bacteria. Our results provide additional bioinformatic evidence for the contribution of the SepRS-SepCysS system for sulfur assimilation and diverse metabolisms which require vast amounts of iron-sulfur enzymes and proteins. Among these biological activities, methanogenesis, methylamine metabolism, and organohalide respiration may have local and global effects on earth. Taken together, uncultured bacteria and archaea provide an expanded record of the evolution of the genetic code.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

CceR and AkgR Regulate Central Carbon and Energy Metabolism in Alphaproteobacteria

Many pathways of carbon and energy metabolism are conserved across the phylogeny, but the networks that regulate their expression or activity often vary considerably among organisms. In this work, we show that two previously uncharacterized transcription factors (TFs) are direct regulators of genes encoding enzymes of central carbon and energy metabolism in the alphaproteobacterium Rhodobacter sphaeroides. The LacI family member CceR (RSP_1663) directly represses genes encoding enzymes in the Entner-Doudoroff pathway, while activating those encoding the F 1 F 0 ATPase and enzymes of the tricarboxylic acid (TCA) cycle and gluconeogenesis, providing a direct transcriptional network connection between carbon and energy metabolism. We identified bases that are important for CceR DNA binding and showed that DNA binding by this TF is inhibited by 6-phosphogluconate. We also showed that the GntR family TF AkgR (RSP_0981) directly activates genes encoding several TCA cycle enzymes, and we identified conditions where its activity is increased. The properties of single and double ΔCceR and ΔAkgR mutants illustrate that these 2 TFs cooperatively regulate carbon and energy metabolism. Comparative genomic analysis indicates that CceR and AkgR orthologs are found in other alphaproteobacteria, where they are predicted to have a conserved function in regulating central carbon metabolism. Our characterization of CceR and AkgR has provided important new insight into the networks that control central carbon and energy metabolism in alphaproteobacteria that can be exploited to modify or engineer new traits in these widespread and versatile bacteria.

Microbiology↗
DOE OSTI2016

Proteome Remodeling in Response to Sulfur Limitation in “ Candidatus Pelagibacter ubique”

“ Ca . Pelagibacter ubique” is a key driver of marine biogeochemistry cycles and a model for understanding how minimal genomes evolved in free-living anucleate organisms. This study explores the unusual sulfur acquisition strategy that has evolved in these cells, which lack assimilatory sulfate reduction and instead rely on reduced sulfur compounds found in oxic marine environments to meet their cellular quotas. Our findings demonstrate that the sulfur acquisition systems are constitutively expressed but the enzymatic steps leading to the essential sulfur-containing amino acid methionine are regulated by a unique array of riboswitches and genes, many of which are encoded in a rapidly evolving genome region. These findings support mounting evidence that streamlined cells have evolved regulatory mechanisms that minimize transcriptional switching and, unexpectedly, localize essential sulfur acquisition genes in a genome region normally associated with adaption to environmental variation.

Smith, Daniel P.↗
DOE OSTI2025

Floodplain nitrifiers harbor the genetic potential for utilizing a wide range of organic nitrogen compounds

Organic compounds such as urea and cyanate can serve as nitrogen (N) sources for nitrifying microorganisms, including ammonia-oxidizing archaea (AOA) and bacteria (AOB), complete ammonia-oxidizing (comammox) bacteria, and nitrite-oxidizing bacteria (NOB). Here we investigated metagenome-assembled genomes (MAGs) for all four nitrifier guilds generated from hydrologically variable floodplain sediments of the Wind River Basin (WRB; Riverton, WY, USA) for their genetic potential to utilize organic N compounds. A vast majority of WRB nitrifier MAGs harbored urease (ure) and at least one urea transporter ( utp, urt, dur3 ). AOA were the most abundant and phylogenetically diverse nitrifiers in WRB floodplain sediments. Several AOA MAGs encoded cyanase ( cynS ), nitrilase ( nit1 ), omega-amidase ( nit2 ), nitrile hydratase ( nthA ), and genes related to purine degradation, including biuret hydrolase ( biuH ), oxamic transcarbamylase ( allFGH ), and catabolic carbamate kinase ( allK ). AOA often encoded an uncharacterized amidohydrolase collocated with biuH , rather than allophanate hydrolase ( atzF ). A small number of AOA encoded atzF , functioning in an unknown pathway. AOB and comammox were of relatively low abundance and taxonomic diversity and were present only at certain depths in WRB; however, they encoded triuret/biuret degradation genes ( trtA, biuH , and atzH ), and in comammox, these genes were also collocated with allFGHK . The genetic potential of ammonia oxidizers in the WRB floodplain suggests that organic N may support nitrification in this system. The proposed pathways for utilizing purine degradation products other than urea potentially expand the known metabolic capabilities of AOA, AOB, and comammox bacteria and reveal the possibility for cryptic N cycling between microbial community members.

floodplain↗
DOE OSTI2019

Energy Conservation in Distributed Interference as a Guarantee for Detecting a Detector Blinding Attack in Quantum Cryptography

An avalanche single-photon detector blinding attack is one of the methods for quantum hacking of quantum key distribution (QKD) systems. The attack was experimentally demonstrated for both phase- and polarization-encoded QKD systems. During this attack, an eavesdropper knows the entire key, does not produce errors and саnnot be detected. However, the phase encoding has neglected some significant features of the photocount statistics in the receiving party. It is shown in the paper at the level of fundamental principles that this attack changes the photocount statistics and leads to the detection of an eavesdropper. Expressions for the secret key length are obtained for this attack. This does not require any changes in the design and control electronics of the phase-encoded QKD system, and only changes in processing the results of registration of quantum states are sufficient. At the same time, the secret key vulnerability and compromise in polarization-encoded QKD systems is an existing fact rather than a potential menace.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Genome analysis of Daldinia eschscholtzii strains UM 1400 and UM 1020, wood-decaying fungi isolated from human hosts

Background: Daldinia eschscholtzii is a wood-inhabiting fungus that causes wood decay under certain conditions. It has a broad host range and produces a large repertoire of potentially bioactive compounds. However, there is no extensive genome analysis on this fungal species. Results: Two fungal isolates (UM 1400 and UM 1020) from human specimens were identified as Daldinia eschscholtzii by morphological features and ITS-based phylogenetic analysis. Both genomes were similar in size with 10,822 predicted genes in UM 1400 (35.8 Mb) and 11,120 predicted genes in UM 1020 (35.5 Mb). A total of 751 gene families were shared among both UM isolates, including gene families associated with fungus-host interactions. In the CAZyme comparative analysis, both genomes were found to contain arrays of CAZyme related to plant cell wall degradation. Genes encoding secreted peptidases were found in the genomes, which encode for the peptidases involved in the degradation of structural proteins in plant cell wall. In addition, arrays of secondary metabolite backbone genes were identified in both genomes, indicating of their potential to produce bioactive secondary metabolites. Both genomes also contained an abundance of gene encoding signaling components, with three proposed MAPK cascades involved in cell wall integrity, osmoregulation, and mating/filamentation. Besides genomic evidence for degrading capability, both isolates also harbored an array of genes encoding stress response proteins that are potentially significant for adaptation to living in the hostile environments. In conclusion: Our genomic studies provide further information for the biological understanding of the D. eschscholtzii and suggest that these wood-decaying fungi are also equipped for adaptation to adverse environments in the human host.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Enzymes involved in the anaerobic degradation of phenol by the sulfate-reducing bacterium Desulfatiglans anilini

Background: The sulfate-reducing bacterium Desulfatiglans anilini can grow with phenol as sole source of carbon and energy under strictly anaerobic, sulfate-reducing conditions. In the nitrate-reducing bacterium Thauera aromatica, the enzymes involved in phenol degradation have been well elucidated, whereas the anaerobic phenol degradation pathway by D. anilini was not studied in detail yet. Results: The pathway of anaerobic phenol degradation by the sulfate-reducing bacterium Desulfatiglans anilini was studied by identification of genes coding for phenylphosphate synthase (encoded by pps genes) and phenylphosphate carboxylase (encoded by ppc genes) in the genome of D. anilini, by analysis of the transcription and translation of pps-ppc genes, and by measurement of phenylphosphate synthase activity in cell-free extracts of phenol-grown cells. The majority of genes involved in phenol degradation were found to be organized in one gene cluster. The gene cluster contained genes ppsα (phenylphosphate synthase alpha subunit), ppsβ (phenylphosphate synthase beta subunit), ppcβ (phenylphosphate carboxylase beta subunit), as well as 4- hydroxybenzoyl-CoA ligase and 4-hydroxylbenzoyl-CoA reductase-encoding genes. The genes ppsγ (phenylphosphate synthase gamma subunit), ppcα (phenylphosphate carboxylase alpha subunit) and ppcδ (phenylphosphate carboxylase delta subunit) were located elsewhere in the genome of D. anilini, and no obvious homologue of ppcγ (phenylphosphate carboxylase gamma subunit) was found in the genome. Induction of genes pps and ppc during growth on phenol was confirmed by reverse transcription polymerase chain reaction. Total proteome analysis revealed that the abundance of enzymes encoded by the gene cluster under study was much higher in phenol-grown cells than that in benzoate-grown cells. In in-vitro enzyme assays with cell-free extracts of phenol-grown cells, phenylphosphate was formed from phenol in the presence of ATP, Mg2+, Mn2+, K+ as co-factors. Conclusions: The genes coding for enzymes involved in the anaerobic phenol degradation pathway were identified in the sulfate-reducing bacterium D. anilini. The results indicate that the first steps of anaerobic phenol degradation in D. anilini are phosphorylation of phenol to phenylphosphate by phenylphosphate synthase and carboxylation of phenylphosphate by phenylphosphate carboxylase.

Phenylphosphate carboxylase↗
DOE OSTI2010

Fourier analysis for hydrostatic pressure sensing in a polarization-maintaining photonic crystal fiber

.We measured the hydrostatic pressure dependence of the birefringence and birefringent dispersion of a Sagnac interferometric sensor incorporating a length of highly birefringent photonic crystal fiber using Fourier analysis. Sensitivity of both the phase and chirp spectra to hydrostatic pressure is demonstrated. Using this analysis, phase-based measurements showed a good linearity with an effective sensitivity of 9.45nm/MPa and an accuracy of {+-}7.8kPa using wavelength-encoded data and an effective sensitivity of -55.7cm{sup -1}/MPa and an accuracy of {+-}4.4kPa using wavenumber-encoded data. Chirp-based measurements, though nonlinear in response, showed an improvement in accuracy at certain pressure ranges with an accuracy of {+-}5.5kPa for the full range of measured pressures using wavelength-encoded data and dropping to within {+-}2.5kPa in the range of 0.17 to 0.4MPa using wavenumber-encoded data. Improvements of the accuracy demonstrated the usefulness of implementing chirp-based analysis for sensing purposes.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2014

A taxonomy of bacterial microcompartment loci constructed by a novel scoring method

Bacterial microcompartments (BMCs) are proteinaceous organelles involved in both autotrophic and heterotrophic metabolism. All BMCs share homologous shell proteins but differ in their complement of enzymes; these are typically encoded adjacent to shell protein genes in genetic loci, or operons. To enable the identification and prediction of functional (sub)types of BMCs, we developed LoClass, an algorithm that finds putative BMC loci and inventories, weights, and compares their constituent pfam domains to construct a locus similarity network and predict locus (sub)types. In addition to using LoClass to analyze sequences in the Non-redundant Protein Database, we compared predicted BMC loci found in seven candidate bacterial phyla (six from single-cell genomic studies) to the LoClass taxonomy. Together, these analyses resulted in the identification of 23 different types of BMCs encoded in 30 distinct locus (sub)types found in 23 bacterial phyla. These include the two carboxysome types and a divergent set of metabolosomes, BMCs that share a common catalytic core and process distinct substrates via specific signature enzymes. Furthermore, many Candidate BMCs were found that lack one or more core metabolosome components, including one that is predicted to represent an entirely new paradigm for BMC-associated metabolism, joining the carboxysome and metabolosome. By placing these results in a phylogenetic context, we provide a framework for understanding the horizontal transfer of these loci, a starting point for studies aimed at understanding the evolution of BMCs. This comprehensive taxonomy of BMC loci, based on their constituent protein domains, foregrounds the functional diversity of BMCs and provides a reference for interpreting the role of BMC gene clusters encoded in isolate, single cell, and metagenomic data. Many loci encode ancillary functions such as transporters or genes for cofactor assembly; this expanded vocabulary of BMC-related functions should be useful for design of genetic modules for introducing BMCs in bioengineering applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Comparative Genome Structure, Secondary Metabolite, and Effector Coding Capacity across Cochliobolus Pathogens

The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25 higher than those between inbred lines and 50 lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Novel Plasmids and Resistance Phenotypes in Yersinia pestis : Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance

Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Involvement of a Bacterial Microcompartment in the Metabolism of Fucose and Rhamnose by Clostridium phytofermentans

Clostridium phytofermentans, an anaerobic soil bacterium, can directly convert plant biomass into biofuels. The genome of C. phytofermentans contains three loci with genes encoding shell proteins of bacterial microcompartments (BMC), organelles composed entirely of proteins. One of the BMC loci has homology to a BMC-encoding locus implicated in the conversion of fucose to propanol and propionate in a human gut commensal, Roseburia inulinivorans. We hypothesized that it had a similar role in C. phytofermentans. When C. phytofermentans was grown on fucose, the major products identified were ethanol, propanol and propionate. Transmission electron microscopy of fucose- and rhamnose-grown cultures revealed polyhedral structures, presumably BMCs. Microarray analysis indicated that during growth on fucose, operons coding for the BMC locus, fucose dissimilatory enzymes, and an ATP-binding cassette transporter became the dominant transcripts. These data are consistent with fucose fermentation producing a 1,2-propanediol intermediate that is further metabolized in the microcompartment encoded in the BMC locus. Growth on another deoxyhexose sugar, rhamnose, resulted in the expression of the same BMC locus and similar fermentation products. However, a different set of dissimilatory enzymes and transport system genes were induced. Quite surprisingly, growth on fucose or rhamnose also led to the expression of a diverse array of complex plant polysaccharide-degrading enzymes. Based on physiological, genomic, and microarray analyses, we propose a model for the fermentation of fucose and rhamnose in C. phytofermentans that includes enzymes encoded in the same BMC locus. Comparative genomic analysis suggests that this BMC may be present in other clostridial species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Human Sensorimotor Cortex Control of Directly Measured Vocal Tract Movements during Vowel Production

During speech production, we make vocal tract movements with remarkable precision and speed. Our understanding of how the human brain achieves such proficient control is limited, in part due to the challenge of simultaneously acquiring high-resolution neural recordings and detailed vocal tract measurements. To overcome this challenge, we combined ultrasound and video monitoring of the supralaryngeal articulators (lips, jaw, and tongue) with electrocorticographic recordings from the cortical surface of 4 subjects (3 female, 1 male) to investigate how neural activity in the ventral sensory-motor cortex (vSMC) relates to measured articulator movement kinematics (position, speed, velocity, acceleration) during the production of English vowels. We found that high-gamma activity at many individual vSMC electrodes strongly encoded the kinematics of one or more articulators, but less so for vowel formants and vowel identity. Neural population decoding methods further revealed the structure of kinematic features that distinguish vowels. Encoding of articulator kinematics was sparsely distributed across time and primarily occurred during the time of vowel onset and offset. In contrast, encoding was low during the steady-state portion of the vowel, despite sustained neural activity at some electrodes. Significant representations were found for all kinematic parameters, but speed was the most robust. These findings enabled by direct vocal tract monitoring demonstrate novel insights into the representation of articulatory kinematic parameters encoded in the vSMC during speech production.

47 OTHER INSTRUMENTATION↗
DOE OSTI2017

Hidden Chloroplast Functions Revealed Through Deep Genomic Analysis

Photosynthesis is a highly complex and orchestrated process that is tuned to plant development and the environment. This project has focused on the gene regulatory mechanisms underlying the elaboration of the photosynthetic apparatus. Particular emphasis has been placed on the regulation of genes encoded in the chloroplast compartment, where photosynthesis takes place. These genes specify both major core proteins of the photosynthetic complexes, as well as proteins that have structural or regulatory properties. The project initially identified structures and sequences in the mRNAs encoding these proteins, that allowed them to be properly regulated during plant development, as well as regulatory proteins that interact with these sequences and structures. It was shown that much of the regulation of chloroplast genes was exerted at the RNA level, rather than at the level of gene transcription. Then, insights were obtained into the enzyme functions that are required to express these RNAs correctly. A series of ribonucleases was studied, with each one having particular specificities and roles in RNA maturation and decay. In the latter part of the project, new genomics tools were employed to study gene regulation in a data-intensive and exploratory manner. Through this work, a new class of “non-coding” and mainly antisense RNAs was identified in chloroplasts, and some of these appear to in fact encode novel proteins that may have unstudied roles in photosynthesis. Overall, the project has taken a trajectory from gene-by-gene analysis to a holistic study of chloroplast coding capacity, including opening the door to identifying new chloroplast-encoded photosynthetic functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

LLNL FESP Theory Highlights: October 2024

I. Novikau, I. Y. Dodin, E. A. Startsev, I. Joseph, Quantum algorithms for simulating dissipative linear and nonlinear dynamics of plasmas. Invited talk at the 66th Annual Meeting of the APS Division of Plasma Physics, Atlanta, Georgia. Novikau I., Dodin I.Y., Startsev E.A., Encoding of linear kinetic plasma problems in quantum circuits via data compression, Journal of Plasma Physics. 2024;90(4):805900401, doi:10.1017/S0022377824000795. We propose an algorithm for encoding linear kinetic plasma problems in quantum circuits. The focus is on modelling electrostatic linear waves in a one-dimensional Maxwellian electron plasma. The waves are described by the linearized Vlasov–Ampère system with a spatially localized external current that drives plasma oscillations. This system is formulated as a boundary-value problem and cast in the form of a linear vector equation to be solved by using the quantum signal processing algorithm. The latter requires encoding of a matrix in a quantum circuit as a sub-block of a unitary matrix. We propose how to encode in a circuit in a compressed form and discuss how the resulting circuit scales with the problem size and the desired precision.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2010

Comparative Metagenomics of Freshwater Microbial Communities

Previous analyses of a microbial metagenome from uranium and nitric-acid contaminated groundwater (FW106) showed significant environmental effects resulting from the rapid introduction of multiple contaminants. Effects include a massive loss of species and strain biodiversity, accumulation of toxin resistant genes in the metagenome and lateral transfer of toxin resistance genes between community members. To better understand these results in an ecological context, a second metagenome from a pristine groundwater system located along the same geological strike was sequenced and analyzed (FW301). It is hypothesized that FW301 approximates the ancestral FW106 community based on phylogenetic profiles and common geological parameters; however, even if is not the case, the datasets still permit comparisons between healthy and stressed groundwater ecosystems. Complex carbohydrate metabolism has been almost entirely lost in the stressed ecosystem. In contrast, the pristine system encodes a wide diversity of complex carbohydrate metabolism systems, suggesting that carbon turnover is very rapid and less leaky in the healthy groundwater system. FW301 encodes many (~;;160+) carbon monoxide dehydrogenase genes while FW106 encodes none. This result suggests that the community is frequently exposed to oxygen from aerated rainwater percolating into the subsurface, with a resulting high rate of carbon metabolism and CO production. When oxygen levels fall, the CO then serves as a major carbon source for the community. FW301 appears to be capable of CO2 fixation via the reductive carboxylase (reverse TCA) cycle and possibly acetogenesis, activities; these activities are lacking in the heterotrophic FW106 system which relies exclusively on respiration of nitrate and/or oxygen for energy production. FW301 encodes a complete set of B12 biosynthesis pathway at high abundance suggesting the use of sodium gradients for energy production in the healthy groundwater community. Overall comparative analysis suggests that the introduction of contaminants is accompanied by a decrease in biodiversity, loss of nutrient cycling, less metabolic diversity, increased respiration and dominance by r-strategists. These results are consistent with trends predicted for stressed ecosystems.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Evidence for Highly Variable, Region-Specific Patterns of T-Cell Epitope Mutations Accumulating in Mycobacterium tuberculosis Strains

Vaccines that confer protection through induction of adaptive T-cell immunity rely on understanding T-cell epitope (TCE) evolution induced by immune escape. This is poorly understood in tuberculosis (TB), an ancient, chronic disease, where CD4 T-cell immunity is of recognized importance. We probed 905 functionally validated, curated human CD4 T cell epitopes in 79 Mycobacterium tuberculosis (Mtb) whole genomes from India. This screen resulted in identifying 64 mutated epitopes in these strains initially using a computational pipeline and subsequently verified by single nucleotide polymorphism (SNP) analysis. SNP based phylogeny revealed the 79 Mtb strains to cluster to East African Indian (EAI), Central Asian Strain (CAS), and Beijing (BEI) lineages. Eighty-nine percent of the mutated T-cell epitopes (mTCEs) identified in the 79 Mtb strains from India has not previously been reported. These mTCEs were encoded by genes with high nucleotide diversity scores including seven mTCEs encoded by six antigens in the top 10% of rapidly divergent Mtb genes encoded by these strains. Using a T cell functional assay readout, we demonstrate 62% of mTCEs tested to significantly alter CD4 T-cell IFNγ and/or IL2 secretion with associated changes in predicted HLA-DR binding affinity: the gain of function mutations displayed higher predicted HLA-DR binding affinity and conversely mutations resulting in loss of function displayed lower predicted HLA-DR binding affinity. Most mutated antigens belonged to the cell wall/cell processes, and, intermediary metabolism and respiration families though all known Mtb proteins encoded mutations. Analysis of the mTCEs in an SNP database of 5,310 global Mtb strains identified 82% mTCEs to be significantly more prevalent in Mtb strains isolated from India, including 36 mTCEs identified exclusively in strains from India. These epitopes had a significantly higher predicted binding affinity to HLA-DR alleles that were highly prevalent in India compared to HLA-DR alleles rare in India, highlighting HLA-DR maybe an important driver of these mutations. This first evidence of region-specific TCE mutations potentially employed by Mtb to escape host immunity has important implications for TB vaccine design.

59 BASIC BIOLOGICAL SCIENCES↗