Contribution of the Oral and Gastrointestinal Microbiomes to Bloodstream Infections in Leukemia Patients

Bloodstream infections (BSIs) pose a significant mortality risk for acute myeloid leukemia (AML) patients. It has been previously reported that intestinal domination (\u3e30% 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

The Assembled Genome of the Stroke-Prone Spontaneously Hypertensive Rat

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

Characterization of agr Groups of Staphylococcus pseudintermedius Isolates from Dogs in Texas

Staphylococcus pseudintermedius is an important disease-causing bacterium in dogs and is recognized as a growing threat to human health. Due to increasing multidrug resistance, discovery of alternative methods for treatment of these infections is vital. Interference with one target for alternative treatment, the quorum sensing system agr, has demonstrated clinical improvement of infections in S. aureus animal models. In this study, we sequenced and characterized 160 clinical S. pseudintermedius isolates and their agr systems in order to increase understanding of the epidemiology of the agr group and clarify its associations with types of infection and antimicrobial resistance. We found that isolates with agr type II were significantly less common than other agr types in diseased dogs. This provides valuable information to veterinary clinical microbiologists and clinicians, especially as less research has been performed on infection associations of agr and its therapeutic potential in S. pseudintermedius than in S. aureus.Staphylococcus pseudintermedius is an important canine pathogen implicated in an increasing number of human infections. Along with rising levels of methicillin and multidrug resistance, staphylococcal biofilms are a complicating factor for treatment and contribute to device, implant, and surgical infections. Staphylococcal virulence, including biofilm formation, is regulated in part by the quorum sensing accessory gene regulator system (agr). The signal molecule for agr, known as the autoinducing peptide molecule, contains polymorphisms that result in the formation of distinct groups. In S. pseudintermedius, 4 groups (i.e., groups I, II, III, and IV) have been identified but not comprehensively examined for associations with infection type, virulence factor carriage, or phylogenetic relationships—all of which have been found to be significant in S. aureus. In this study, 160 clinical canine isolates from Texas, including isolates from healthy dogs (n = 40) and 3 different infection groups (pyoderma, urinary tract, and surgical, n = 40 each), were sequenced. The agr group, biofilm-producing capabilities, toxin gene carriage, antimicrobial resistance, and sequence type (ST) were identified for all isolates. While no significant associations were discovered among the clinical infection types and agr groups, agr II isolates were significantly less common than any other group in diseased dogs. Furthermore, agr II isolates were less likely than other agr groups to be multidrug resistant and to carry toxin genes expA and sec-canine. Fifty-two (33%) of the 160 isolates were methicillin resistant, and the main sequence types (ST64, ST68, ST71, ST84, ST150, and ST155) of methicillin-resistant strains of S. pseudintermedius (MRSP) were identified for the geographic region

Differences in the genome, methylome, and transcriptome do not differentiate isolates of Streptococcus equi subsp. equi from horses with acute clinical signs from isolates of inapparent carriers

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

Image_4_Brain region dependent molecular signatures and myelin repair following chronic demyelination.jpeg

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.</p

Table_3_Brain region dependent molecular signatures and myelin repair following chronic demyelination.XLSX

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.</p

Table_4_Brain region dependent molecular signatures and myelin repair following chronic demyelination.XLSX

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.</p

Image_3_Brain region dependent molecular signatures and myelin repair following chronic demyelination.jpeg

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.</p

Image_5_Brain region dependent molecular signatures and myelin repair following chronic demyelination.jpeg

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.</p