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1.
Front Cell Neurosci ; 17: 1169786, 2023.
Article in English | MEDLINE | ID: mdl-37180951

ABSTRACT

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyelination. Extensive remyelination occurred after both the acute and chronic insults, but with less robust glial responses and slower myelin recovery in the chronic phase. Axonal damage was found at the ultrastructural level in the chronically demyelinated corpus callosum and in remyelinated axons in the somatosensory cortex. Unexpectedly, we observed the development of functional motor deficits after chronic remyelination. RNA sequencing of isolated brain regions revealed significantly altered transcripts across the corpus callosum, cortex and hippocampus. Pathway analysis identified selective upregulation of extracellular matrix/collagen pathways and synaptic signaling in the chronically de/remyelinating white matter. Our study demonstrates regional differences of intrinsic reparative mechanisms after a chronic demyelinating insult and suggests a potential link between long-term motor function alterations and continued axonal damage during chronic remyelination. Moreover, the transcriptome dataset of three brain regions and over an extended de/remyelination period provides a valuable platform for a better understanding of the mechanisms of myelin repair as well as the identification of potential targets for effective remyelination and neuroprotection for progressive MS.

2.
Biol Sex Differ ; 14(1): 19, 2023 04 15.
Article in English | MEDLINE | ID: mdl-37060018

ABSTRACT

BACKGROUND: Prenatal alcohol (ethanol) exposure (PAE) results in brain growth restriction, in part, by reprogramming self-renewal and maturation of fetal neural stem cells (NSCs) during neurogenesis. We recently showed that ethanol resulted in enrichment of both proteins and pro-maturation microRNAs in sub-200-nm-sized extracellular vesicles (EVs) secreted by fetal NSCs. Moreover, EVs secreted by ethanol-exposed NSCs exhibited diminished efficacy in controlling NSC metabolism and maturation. Here we tested the hypothesis that ethanol may also influence the packaging of RNAs into EVs from cell-of-origin NSCs. METHODS: Sex-specified fetal murine iso-cortical neuroepithelia from three separate pregnancies were maintained ex vivo, as neurosphere cultures to model the early neurogenic niche. EVs were isolated by ultracentrifugation from NSCs exposed to a dose range of ethanol. RNA from paired EV and cell-of-origin NSC samples was processed for ribosomal RNA-depleted RNA sequencing. Differential expression analysis and exploratory weighted gene co-expression network analysis (WGCNA) identified candidate genes and gene networks that were drivers of alterations to the transcriptome of EVs relative to cells. RESULTS: The RNA content of EVs differed significantly from cell-of-origin NSCs. Biological sex contributed to unique transcriptome variance in EV samples, where > 75% of the most variant transcripts were also sex-variant in EVs but not in cell-of-origin NSCs. WGCNA analysis also identified sex-dependent enrichment of pathways, including dopamine receptor binding and ectoderm formation in female EVs and cell-substrate adhesion in male EVs, with the top significant DEGs from differential analysis of overall individual gene expressions, i.e., Arhgap15, enriched in female EVs, and Cenpa, enriched in male EVs, also serving as WCGNA hub genes of sex-biased EV WGCNA clusters. In addition to the baseline RNA content differences, ethanol exposure resulted in a significant dose-dependent change in transcript expression in both EVs and cell-of-origin NSCs that predominantly altered sex-invariant RNAs. Moreover, at the highest dose, ~ 73% of significantly altered RNAs were enriched in EVs, but depleted in NSCs. CONCLUSIONS: The EV transcriptome is distinctly different from, and more sex-variant than, the transcriptome of cell-of-origin NSCs. Ethanol, a common teratogen, results in dose-dependent sorting of RNA transcripts from NSCs to EVs which may reprogram the EV-mediated endocrine environment during neurogenesis.


Subject(s)
Extracellular Vesicles , MicroRNAs , Neural Stem Cells , Pregnancy , Female , Male , Animals , Mice , Transcriptome , Sex Characteristics , Ethanol/pharmacology , MicroRNAs/metabolism , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism
3.
Front Cell Infect Microbiol ; 13: 1115350, 2023.
Article in English | MEDLINE | ID: mdl-37113133

ABSTRACT

Lyme disease (LD), the most prevalent tick-borne disease of humans in the Northern Hemisphere, is caused by the spirochetal bacterium of Borreliella burgdorferi (Bb) sensu lato complex. In nature, Bb spirochetes are continuously transmitted between Ixodes ticks and mammalian or avian reservoir hosts. Peromyscus leucopus mice are considered the primary mammalian reservoir of Bb in the United States. Earlier studies demonstrated that experimentally infected P. leucopus mice do not develop disease. In contrast, C3H mice, a widely used laboratory strain of Mus musculus in the LD field, develop severe Lyme arthritis. To date, the exact tolerance mechanism of P. leucopus mice to Bb-induced infection remains unknown. To address this knowledge gap, the present study has compared spleen transcriptomes of P. leucopus and C3H/HeJ mice infected with Bb strain 297 with those of their respective uninfected controls. Overall, the data showed that the spleen transcriptome of Bb-infected P. leucopus mice was much more quiescent compared to that of the infected C3H mice. To date, the current investigation is one of the few that have examined the transcriptome response of natural reservoir hosts to Borreliella infection. Although the experimental design of this study significantly differed from those of two previous investigations, the collective results of the current and published studies have consistently demonstrated very limited transcriptomic responses of different reservoir hosts to the persistent infection of LD pathogens. Importance: The bacterium Borreliella burgdorferi (Bb) causes Lyme disease, which is one of the emerging and highly debilitating human diseases in countries of the Northern Hemisphere. In nature, Bb spirochetes are maintained between hard ticks of Ixodes spp. and mammals or birds. In the United States, the white-footed mouse, Peromyscus leucopus, is one of the main Bb reservoirs. In contrast to humans and laboratory mice (e.g., C3H mice), white-footed mice rarely develop clinical signs (disease) despite being (persistently) infected with Bb. How the white-footed mouse tolerates Bb infection is the question that the present study has attempted to address. Comparisons of genetic responses between Bb-infected and uninfected mice demonstrated that, during a long-term Bb infection, C3H mice reacted much stronger, whereas P. leucopus mice were relatively unresponsive.


Subject(s)
Borrelia burgdorferi , Ixodes , Lyme Disease , Animals , Mice , Humans , Peromyscus/microbiology , Transcriptome , Mice, Inbred C3H , Disease Reservoirs , Lyme Disease/microbiology , Borrelia burgdorferi/genetics , Ixodes/microbiology , Gene Expression Profiling
4.
Microbiol Spectr ; 11(3): e0041523, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37022173

ABSTRACT

Bloodstream infections (BSIs) pose a significant mortality risk for acute myeloid leukemia (AML) patients. It has been previously reported that intestinal domination (>30% relative abundance [RA] attributed to a single taxon) with the infecting taxa often precedes BSI in stem cell transplant patients. Using 16S rRNA amplicon sequencing, we analyzed oral and stool samples from 63 AML patients with BSIs to determine the correlation between the infectious agent and microbiome composition. Whole-genome sequencing and antimicrobial susceptibilities were performed on all BSI isolates. Species-level detection of the infectious agent and presence of antibiotic resistance determinants in the stool (blaCTX-M-15, blaCTX-M-14, cfrA, and vanA) were confirmed via digital droplet PCR (ddPCR). Individuals with Escherichia coli (stool P < 0.001), Pseudomonas aeruginosa (oral P = 0.004, stool P < 0.001), and viridans group streptococci (VGS) (oral P = 0.001) bacteremia had a significantly higher relative abundance of those respective genera than other BSI patients, which appeared to be site specific. Although 78% of patients showed presence of the infectious genera in the stool and/or saliva, only 7 exhibited microbiome domination. ddPCR confirmed species specificity of the 16S data and detected the antibiotic resistance determinants found in the BSI isolates within concurrent stools. Although gastrointestinal (GI) domination by an infecting organism was not present at the time of most BSIs in AML, the pathogens, along with AMR elements, were detectable in the majority of patients. Thus, rapid genetic assessment of oral and stool samples for the presence of potential pathogens and AMR determinants might inform personalized therapeutic approaches in immunocompromised patients with suspected infection. IMPORTANCE A major cause of mortality in hematologic malignancy patients is BSI. Previous studies have demonstrated that bacterial translocation from the GI microbiome is a major source of BSIs and is often preceded by increased levels of the infectious taxa in the GI (>30% abundance by 16S rRNA sequencing). In this study, we sought to better understand how domination and abundance levels of the oral and gut microbiome relate to bacteremia occurrence in acute myeloid leukemia patients. We conclude that analyses of both oral and stool samples can help identify BSI and antimicrobial resistance determinants, thus potentially improving the timing and tailoring of antibiotic treatment strategies for high-risk patients.


Subject(s)
Bacteremia , Gastrointestinal Microbiome , Leukemia, Myeloid, Acute , Microbiota , Humans , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Bacteremia/microbiology , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
5.
Hypertension ; 80(1): 138-146, 2023 01.
Article in English | MEDLINE | ID: mdl-36330812

ABSTRACT

BACKGROUND: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease. METHODS: The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, using NCBI automated protocols. We also generated orthogonal single molecule transcript sequence reads (Iso-Seq) from 8 tissues and used them to validate the coding assembly, to annotate the assembly with RNA transcripts representing unique full length transcript isoforms for each gene and to determine whether divergences between RefSeq sequences and the assembly were attributable to assembly errors or polymorphisms. RESULTS: The assembly analysis indicates that this assembly is comparable in contiguity and completeness to the current rat reference assembly, while the use of HiFi sequencing yields an assembly that is more correct at the single base level. Synteny analysis was performed to uncover the extent of synteny and the presence and distribution of chromosomal rearrangements between the reference and this assembly. CONCLUSION: The resulting genome assembly is reference quality and captures significant structural variation.


Subject(s)
Stroke , Humans , Rats , Animals , Rats, Inbred SHR , Stroke/genetics
6.
Microbiol Spectr ; 10(4): e0248421, 2022 08 31.
Article in English | MEDLINE | ID: mdl-35913176

ABSTRACT

Coxiella burnetii requires a type IVB secretion system (T4SS) to promote intracellular replication and virulence. We hypothesized that Coxiella employs its T4SS to secrete effectors that enable stealthy colonization of immune cells. To address this, we used RNA sequencing to compare the transcriptional response of murine bone marrow-derived macrophages (BMDM) infected with those of wild-type Coxiella and a T4SS-null mutant at 8 and 24 h postinfection. We found a T4SS-independent upregulation of proinflammatory transcripts which was consistent with a proinflammatory polarization phenotype. Despite this, infected BMDM failed to completely polarize, as evidenced by modest surface expression of CD38 and CD11c, nitrate production, and reduced proinflammatory cytokine and chemokine secretion compared to positive controls. As these BMDM permitted replication of C. burnetii, we employed them to identify T4SS effectors that are essential in the specific cellular context of a primary macrophage. We found five Himar1 transposon mutants in T4SS effectors that had a replication defect in BMDM but not J774A.1 cells. The mutants were also attenuated in a SCID mouse model of infection. Among these candidate virulence factors, we found that CBU1639 contributed to the inhibition of macrophage proinflammatory responses to Coxiella infection. These data demonstrate that while T4SS is dispensable for the stealthy invasion of primary macrophages, Coxiella has evolved multiple T4SS effectors that specifically target macrophage function to proliferate within that specific cellular context. IMPORTANCE Coxiella burnetii, the causative agent of Q fever, preferentially infects macrophages of the respiratory tract when causing human disease. This work describes how primary macrophages respond to C. burnetii at the earliest stages of infection, before bacterial replication. We found that while infected macrophages increase expression of proinflammatory genes after bacterial entry, they fail to activate the accompanying antibacterial functions that might ultimately control the infection. This disconnect between initial response and downstream function was not mediated by the bacterium's type IVB secretion system, suggesting that Coxiella has other virulence factors that dampen host responses early in the infection process. Nevertheless, we were able to identify several type IVB secreted effectors that were specifically required for survival in macrophages and mice. This work is the first to identify type IVB secretion effectors that are specifically required for infection and replication within primary macrophages.


Subject(s)
Coxiella burnetii , Q Fever , Animals , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Coxiella burnetii/genetics , Host-Pathogen Interactions/physiology , Humans , Macrophages/microbiology , Mice , Mice, SCID , Q Fever/metabolism , Q Fever/microbiology , Virulence Factors/genetics , Virulence Factors/metabolism
7.
Physiol Genomics ; 54(7): 251-260, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35543507

ABSTRACT

Rat genomic tools have been slower to emerge than for those of humans and mice and have remained less thorough and comprehensive. The arrival of a new and improved rat reference genome, mRatBN7.2, in late 2020 is a welcome event. This assembly, like predecessor rat reference assemblies, is derived from an inbred Brown Norway rat. In this "user" survey we hope to provide other users of this assembly some insight into its characteristics and some assessment of its improvements as well as a few caveats that arise from the unique aspects of this assembly. mRatBN7.2 was generated by the Wellcome Sanger Institute as part of the large Vertebrate Genomes Project. This rat assembly has now joined human, mouse, chicken, and zebrafish in the National Center for Biotechnology Information (NCBI)'s Genome Reference Consortium, which provides ongoing curation of the assembly. Here we examine the technical procedures by which the assembly was created and assess how this assembly constitutes an improvement over its predecessor. We also indicate the technical limitations affecting the assembly, providing illustrations of how these limitations arise and the impact that results for this reference assembly.


Subject(s)
Genome , Zebrafish , Animals , Genome/genetics , Genomics/methods , Mice , Rats
8.
Transl Res ; 246: 102-114, 2022 08.
Article in English | MEDLINE | ID: mdl-35351623

ABSTRACT

Electronic cigarette (e-cig) use has increased over the past decade, and exposure to e-cig aerosols during pregnancy raises concern for maternal and fetal health. The developing fetal lung is known to be sensitive to prenatal tobacco product exposure. Utilizing a 3-pronged approach, we examined the effects of prenatal e-cig aerosols with, and without nicotine on respiratory development in a murine model. RNAseq analysis of fetal lungs revealed extensive dysregulation in gene expression. Morphologic assessment of distal airspaces in neonatal lungs display an emphysematic phenotype. Respiratory mechanics of neonates display signs of increased respiratory workload, with increased resistance and decreased compliance. These data are novel and provide evidence that prenatal e-cig exposure may result in altered lung function or development of disease.


Subject(s)
Electronic Nicotine Delivery Systems , Vaping , Aerosols , Animals , Female , Fetus , Mice , Nicotine , Pregnancy , Vaping/adverse effects
9.
Am J Trop Med Hyg ; 105(5): 1227-1229, 2021 09 20.
Article in English | MEDLINE | ID: mdl-34544043

ABSTRACT

To better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant lineage distribution in a college campus population, we carried out viral genome surveillance over a 7-week period from January to March 2021. Among the sequences were three novel viral variants: BV-1 with a B.1.1.7/20I genetic background and an additional spike mutation Q493R, associated with a mild but longer-than-usual COVID-19 case in a college-age person, BV-2 with a T478K mutation on a 20B genetic background, and BV-3, an apparent recombinant lineage. This work highlights the potential of an undervaccinated younger population as a reservoir for the spread and generation of novel variants. This also demonstrates the value of whole genome sequencing as a routine disease surveillance tool.


Subject(s)
COVID-19/virology , Disease Reservoirs/virology , Mutation , SARS-CoV-2/genetics , Students/statistics & numerical data , Universities , Adult , COVID-19/etiology , Genome, Viral , Humans , Neutralization Tests , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Young Adult
10.
mSphere ; 6(4): e0019620, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34346711

ABSTRACT

While Staphylococcus aureus is associated with significant morbidity and mortality in equids (horses, donkeys, and mules), few studies have performed whole-genome sequencing to fully categorize large collections of equine isolates. Such sequencing allows for a comprehensive analysis of the genetic lineage and relationships of isolates, as well as the virulence genes present in each, which can be important for understanding the epidemiology of strains and their range of infections. Seventy-two clinical Staphylococcus aureus isolates from equids were collected at the Texas A&M University Veterinary Medical Teaching Hospital between 2007 and 2017. Whole-genome sequencing was performed to characterize the isolates according to sequence typing, biofilm association, antimicrobial resistance, and toxin gene carriage. Of the 72 isolates, 19% were methicillin resistant, of which the majority belonged to clonal complex 8. Eighteen distinct sequence types (STs) were represented, with the most common being ST1, ST133, ST8, and ST97. Most isolates had weak or negative overall biofilm production. Toxin and antimicrobial resistance gene carriage was varied; of note, this study revealed that a large proportion of North American equine isolates carry the leucocidin PQ toxin (66% of isolates). One isolate (17-021) carried genes imparting lincosamide and high-level mupirocin resistance, a combination not previously reported in equine-derived S. aureus isolates. IMPORTANCE This is one of the first studies to perform whole-genome sequencing (WGS) of a large collection of Staphylococcus aureus isolates, both methicillin resistant and susceptible, collected from horses. A large proportion of the isolates carry leucocidin PQ (LukPQ), making this one of the first reports of such carriage in the United States. The presence of lincosamide and high-level mupirocin resistance in a methicillin-susceptible S. aureus (MSSA) isolate highlights the importance of MSSA as a reservoir of important antimicrobial resistance genes. As microbial resistance genes on mobile genetic elements can pass between S. aureus strains and livestock-associated strains can be transferred to humans, these findings have important public health implications.


Subject(s)
Anti-Bacterial Agents/pharmacology , Carrier State/veterinary , Drug Resistance, Multiple, Bacterial/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/veterinary , Whole Genome Sequencing/methods , Animals , Biofilms , Carrier State/microbiology , Female , Genes, Bacterial/genetics , Genome, Bacterial , Horses , Male , Microbial Sensitivity Tests , Staphylococcal Infections/microbiology , Texas , Virulence/genetics , Virulence Factors/genetics
11.
J Virol ; 95(19): e0239120, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34287047

ABSTRACT

The majority of previously described Staphylococcus aureus bacteriophages belong to three major groups, namely, P68-like podophages, Twort-like or K-like myophages, and a more diverse group of temperate siphophages. Here, we present the following three novel S. aureus "jumbo" phages: MarsHill, Madawaska, and Machias. These phages were isolated from swine production environments in the United States and represent a novel clade of S. aureus myophage. The average genome size for these phages is ∼269 kb with each genome encoding ∼263 predicted protein-coding genes. Phage genome organization and content are similar to those of known jumbo phages of Bacillus sp., including AR9 and vB_BpuM-BpSp. All three phages possess genes encoding complete virion and nonvirion RNA polymerases, multiple homing endonucleases, and a retron-like reverse transcriptase. Like AR9, all of these phages are presumed to have uracil-substituted DNA which interferes with DNA sequencing. These phages are also able to transduce host plasmids, which is significant as these phages were found circulating in swine production environments and can also infect human S. aureus isolates. IMPORTANCE This study describes the comparative genomics of the following three novel S. aureus jumbo phages: MarsHill, Madawaska, and Machias. These three S. aureus myophages represent an emerging class of S. aureus phage. These genomes contain abundant introns which show a pattern consistent with repeated acquisition rather than vertical inheritance, suggesting intron acquisition and loss are active processes in the evolution of these phages. These phages have presumably hypermodified DNA which inhibits sequencing by several different common platforms. Therefore, these phages also represent potential genomic diversity that has been missed due to the limitations of standard sequencing techniques. In particular, such hypermodified genomes may be missed by metagenomic studies due to their resistance to standard sequencing techniques. Phage MarsHill was found to be able to transduce host DNA at levels comparable to that found for other transducing S. aureus phages, making it a potential vector for horizontal gene transfer in the environment.


Subject(s)
Genome, Viral , Myoviridae/genetics , Staphylococcus Phages/genetics , Staphylococcus aureus/virology , Animals , DNA, Viral/genetics , DNA-Directed RNA Polymerases/genetics , Genomics , Introns , Myoviridae/isolation & purification , Myoviridae/physiology , Myoviridae/ultrastructure , Sequence Analysis, DNA , Staphylococcus Phages/isolation & purification , Staphylococcus Phages/physiology , Staphylococcus Phages/ultrastructure , Swine , Transduction, Genetic , Viral Proteins/genetics
12.
PLoS One ; 16(6): e0252804, 2021.
Article in English | MEDLINE | ID: mdl-34125848

ABSTRACT

Streptococcus equi subsp. equi (SEE) is a host-restricted bacterium that causes the common infectious upper respiratory disease known as strangles in horses. Perpetuation of SEE infection appears attributable to inapparent carrier horses because it neither persists long-term in the environment nor infects other host mammals or vectors, and infection results in short-lived immunity. Whether pathogen factors enable SEE to remain in horses without causing clinical signs remains poorly understood. Thus, our objective was to use next-generation sequencing technologies to characterize the genome, methylome, and transcriptome of isolates of SEE from horses with acute clinical strangles and inapparent carrier horses-including isolates recovered from individual horses sampled repeatedly-to assess pathogen-associated changes that might reflect specific adaptions of SEE to the host that contribute to inapparent carriage. The accessory genome elements and methylome of SEE isolates from Sweden and Pennsylvania revealed no significant or consistent differences between acute clinical and inapparent carrier isolates of SEE. RNA sequencing of SEE isolates from Pennsylvania demonstrated no genes that were differentially expressed between acute clinical and inapparent carrier isolates of SEE. The absence of specific, consistent changes in the accessory genomes, methylomes, and transcriptomes of acute clinical and inapparent carrier isolates of SEE indicates that adaptations of SEE to the host are unlikely to explain the carrier state of SEE. Efforts to understand the carrier state of SEE should instead focus on host factors.


Subject(s)
Carrier State/diagnosis , Epigenome/genetics , Genome/genetics , Horse Diseases/diagnosis , Streptococcus/genetics , Transcriptome/genetics , Animals , Carrier State/microbiology , DNA, Bacterial/analysis , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Diagnosis, Differential , Disease Outbreaks , Horse Diseases/epidemiology , Horse Diseases/microbiology , Horses , Pennsylvania/epidemiology , RNA, Bacterial/analysis , RNA, Bacterial/genetics , RNA, Bacterial/isolation & purification , RNA-Seq/methods , Species Specificity , Streptococcus/classification , Streptococcus/physiology , Sweden/epidemiology , Whole Genome Sequencing/methods
13.
iScience ; 24(5): 102439, 2021 May 21.
Article in English | MEDLINE | ID: mdl-33997709

ABSTRACT

Prenatal alcohol exposure (PAE) results in cerebral cortical dysgenesis. Single-cell RNA sequencing was performed on murine fetal cerebral cortical cells from six timed pregnancies, to decipher persistent cell- and sex-specific effects of an episode of PAE during early neurogenesis. We found, in an analysis of 38 distinct neural subpopulations across 8 lineage subtypes, that PAE altered neural maturation and cell cycle and disrupted gene co-expression networks. Whereas most differentially regulated genes were inhibited, particularly in females, PAE also induced sex-independent neural expression of fetal hemoglobin, a presumptive epigenetic stress adaptation. PAE inhibited Bcl11a, Htt, Ctnnb1, and other upstream regulators of differentially expressed genes and inhibited several autism-linked genes, suggesting that neurodevelopmental disorders share underlying mechanisms. PAE females exhibited neural loss of X-inactivation, with correlated activation of autosomal genes and evidence for spliceosome dysfunction. Thus, episodic PAE persistently alters the developing neural transcriptome, contributing to sex- and cell-type-specific teratology.

14.
Microorganisms ; 9(3)2021 Mar 16.
Article in English | MEDLINE | ID: mdl-33809423

ABSTRACT

In 2013, the U.S. Department of Agriculture Food Safety and Inspection Service (USDA-FSIS) began transitioning to whole genome sequencing (WGS) for foodborne disease outbreak- and recall-associated isolate identification of select bacterial species. While WGS offers greater precision, certain hurdles must be overcome before widespread application within the food industry is plausible. Challenges include diversity of sequencing platform outputs and lack of standardized bioinformatics workflows for data analyses. We sequenced DNA from USDA-FSIS approved, non-pathogenic E. coli surrogates and a derivative group of rifampicin-resistant mutants (rifR) via both Oxford Nanopore MinION and Illumina MiSeq platforms to generate and annotate complete genomes. Genome sequences from each clone were assembled separately so long-read, short-read, and combined sequence assemblies could be directly compared. The combined sequence data approach provides more accurate completed genomes. The genomes from these isolates were verified to lack functional key E. coli elements commonly associated with pathogenesis. Genetic alterations known to confer rifR were also identified. As the food industry adopts WGS within its food safety programs, these data provide completed genomes for commonly used surrogate strains, with a direct comparison of sequence platforms and assembly strategies relevant to research/testing workflows applicable for both processors and regulators.

15.
Microbiol Resour Announc ; 9(32)2020 Aug 06.
Article in English | MEDLINE | ID: mdl-32763933

ABSTRACT

The genomes of three clinical isolates of Salmonella enterica subsp. houtenae were sequenced using an Illumina MiSeq instrument. These isolates came from the urine and cerebrospinal fluid of a dog treated for hind-limb paresis with immunosuppressive drugs. S. enterica subsp. houtenae has also been implicated in brain infections in humans.

16.
Microbiol Resour Announc ; 9(32)2020 Aug 06.
Article in English | MEDLINE | ID: mdl-32763944

ABSTRACT

This is a draft genome of an orf virus (ORFV) vaccine strain assembled via long- and short-read hybrid assembly. ORFV is a zoonotic pathogen that affects sheep and goats. The genome of the virus contained in the vaccine was found to have high similarity (98%) to those of other published strains.

17.
Microbiol Resour Announc ; 9(26)2020 Jun 25.
Article in English | MEDLINE | ID: mdl-32586861

ABSTRACT

This is the draft genome of an Erysipelothrix rhusiopathiae strain isolated from the blood of a canine. Initial 16S ribosomal DNA amplification identified the isolate as belonging to the Erysipelothrix genus but could not elucidate the species due to previous misidentification of E. rhusiopathiae and E. tonsillarum The species identification was confirmed by whole-genome sequencing.

18.
Microbiol Resour Announc ; 9(20)2020 May 14.
Article in English | MEDLINE | ID: mdl-32409543

ABSTRACT

This is a report of two Bacillus safensis genomes sequenced from separate cultures isolated from the uterus of a 16-year-old Westphalian mare that aborted a dead fetus. This strain represents the first case of a B. safensis-associated equine abortion and the first case of infection caused by this bacterium.

19.
Vet Microbiol ; 243: 108638, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32273017

ABSTRACT

Strangles, caused by Streptococcus equi subspecies equi (S. equi) is an infectious disease of horses with worldwide distribution, but there are limited data available regarding strain variation using whole genome sequencing among and within outbreaks in the United States (US), and how US isolates compare with S. equi isolated globally. To address this knowledge-gap, we compared the whole genomes of 54 S. equi isolates from Texas and Kentucky and those of 230 publicly available sequences of S. equi isolates collected from other countries. Our results show that despite minimal variation among isolates within an outbreak some mutations do occur among individual outbreak isolates. Some S. equi strains from the US are closely related to S. equi isolates from other countries, likely reflecting international dissemination of isolates. Collectively, these data improve our understanding of phenotypic and genotypic variation of isolates within an outbreak, and the international distribution of S. equi. We also identify a novel variant of the S. equi M-protein, and observed cases of strangles that were caused by the modified-live vaccine but that were not recognized as vaccine-associated at the time of clinical sample submission.


Subject(s)
Disease Outbreaks/veterinary , Horse Diseases/microbiology , Streptococcal Infections/veterinary , Streptococcus/genetics , Whole Genome Sequencing , Animals , Bacterial Proteins/genetics , Genetic Variation , Genotype , Horses/microbiology , Internationality , Kentucky/epidemiology , Mutation , Phylogeny , Sequence Analysis, DNA , Texas/epidemiology
20.
Microbiol Resour Announc ; 9(13)2020 Mar 26.
Article in English | MEDLINE | ID: mdl-32217678

ABSTRACT

This is an announcement for the genome sequence of a clinical isolate of Salmonella enterica subsp. arizonae isolated from the urine and prostate of a 6-year-old male Labrador retriever. This is one of the few reports of a Salmonella enterica subsp. arizonae isolate cultured from canine urine.

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