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  1. AU="Ram-Mohan, Nikhil"
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  1. Article ; Online: Re-visiting humoral constitutive antibacterial heterogeneity in bloodstream infections.

    Abe, Ryuichiro / Ram-Mohan, Nikhil / Yang, Samuel

    The Lancet. Infectious diseases

    2023  Volume 24, Issue 4, Page(s) e245–e251

    Abstract: Although cellular immunity has garnered much attention in the era of single-cell technologies, humoral innate immunity has receded in priority due to its presumed limited roles. Hence, despite the long-recognised bactericidal activity of serum-a ... ...

    Abstract Although cellular immunity has garnered much attention in the era of single-cell technologies, humoral innate immunity has receded in priority due to its presumed limited roles. Hence, despite the long-recognised bactericidal activity of serum-a functional characteristic of constitutive humoral immunity-much remains unclear regarding mechanisms underlying its inter-individual heterogeneity and clinical implications in bloodstream infections. Recent work suggests that the immediate antimicrobial effect of humoral innate immunity contributes to suppression of the excessive inflammatory responses to infection by reducing the amount of pathogen-associated molecular patterns. In this Personal View, we propose the need to re-explore factors underlying the inter-individual heterogeneity in serum antibacterial competence as a new approach to better understand humoral innate immunity and revisit the clinical use of measuring serum antibacterial activity in the management of bacterial bloodstream infections. Given the current emphasis on subtyping sepsis, a serum bactericidal assay might prove useful in defining a distinct sepsis endotype, to enable more personalised management.
    MeSH term(s) Humans ; Sepsis/drug therapy ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections ; Bacteria ; Immunity, Innate
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2023-11-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(23)00494-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Neutrophil Extracellular Traps have DNAzyme activity that drives bactericidal potential.

    Ku, Ti-Hsuan / Ram-Mohan, Nikhil / Zudock, Elizabeth J / Abe, Ryuichiro / Yang, Samuel

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The mechanisms of bacterial killing by neutrophil extracellular traps (NETs) are unclear. DNA, the largest component of NETs is believed to merely be a scaffold with minimal antimicrobial activity through the charge of the backbone. Here, we report that ... ...

    Abstract The mechanisms of bacterial killing by neutrophil extracellular traps (NETs) are unclear. DNA, the largest component of NETs is believed to merely be a scaffold with minimal antimicrobial activity through the charge of the backbone. Here, we report that NETs DNA is beyond a scaffold and produces hydroxyl free radicals through the spatially concentrated G-quadruplex/hemin DNAzyme complexes, driving bactericidal effects. Immunofluorescence staining showed colocalization of G-quadruplex and hemin in extruded NETs DNA, and Amplex UltraRed assay portrayed its peroxidase activity. Proximity labeling of bacteria revealed localized concentration of radicals resulting from NETs bacterial trapping.
    Language English
    Publishing date 2023-10-24
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.23.563618
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Rapid molecular phenotypic antimicrobial susceptibility test for

    Tjandra, Kristel C / Ram-Mohan, Nikhil / Abe, Ryuichiro / Wang, Tza-Huei / Yang, Samuel

    bioRxiv : the preprint server for biology

    2023  

    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.01.530513
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Rapid Molecular Phenotypic Antimicrobial Susceptibility Test for

    Tjandra, Kristel C / Ram-Mohan, Nikhil / Abe, Ryuichiro / Wang, Tza-Huei / Yang, Samuel

    ACS infectious diseases

    2023  Volume 9, Issue 5, Page(s) 1160–1167

    Abstract: Neisseria ... ...

    Abstract Neisseria gonorrhoeae
    MeSH term(s) Humans ; Neisseria gonorrhoeae/genetics ; Anti-Bacterial Agents/pharmacology ; Ceftriaxone/pharmacology ; Gonorrhea ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Ciprofloxacin/pharmacology ; Anti-Infective Agents/pharmacology ; Polymerase Chain Reaction
    Chemical Substances Anti-Bacterial Agents ; Ceftriaxone (75J73V1629) ; propidium monoazide ; Ciprofloxacin (5E8K9I0O4U) ; Anti-Infective Agents
    Language English
    Publishing date 2023-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.3c00096
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Comparative Metatranscriptomics of Periodontitis Supports a Common Polymicrobial Shift in Metabolic Function and Identifies Novel Putative Disease-Associated ncRNAs.

    Ram-Mohan, Nikhil / Meyer, Michelle M

    Frontiers in microbiology

    2020  Volume 11, Page(s) 482

    Abstract: Periodontitis is an inflammatory disease that deteriorates bone supporting teeth afflicting ∼743 million people worldwide. Bacterial communities associated with disease have been classified into red, orange, purple, blue, green, and yellow complexes ... ...

    Abstract Periodontitis is an inflammatory disease that deteriorates bone supporting teeth afflicting ∼743 million people worldwide. Bacterial communities associated with disease have been classified into red, orange, purple, blue, green, and yellow complexes based on their roles in the periodontal pocket. Previous metagenomic and metatranscriptomics analyses suggest a common shift in metabolic signatures in disease vs. healthy communities with up-regulated processes including pyruvate fermentation, histidine degradation, amino acid metabolism, TonB-dependent receptors. In this work, we examine existing metatranscriptome datasets to identify the commonly differentially expressed transcripts and potential underlying RNA regulatory mechanisms behind the metabolic shifts. Raw RNA-seq reads from three studies (including 49 healthy and 48 periodontitis samples) were assembled into transcripts
    Language English
    Publishing date 2020-04-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2020.00482
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases.

    Haddock, Naomi L / Barkal, Layla J / Ram-Mohan, Nikhil / Kaber, Gernot / Chiu, Charles Y / Bhatt, Ami S / Yang, Samuel / Bollyky, Paul L

    Nature microbiology

    2023  Volume 8, Issue 8, Page(s) 1495–1507

    Abstract: Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a ... ...

    Abstract Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a computational pipeline to identify sequences associated with bacteriophages and their bacterial hosts in cell-free DNA from plasma samples. Analysis of two independent cohorts, including a Stanford Cohort of 61 septic patients and 10 controls and the SeqStudy cohort of 224 septic patients and 167 controls, reveals a circulating phageome in the plasma of all sampled individuals. Moreover, infection is associated with overrepresentation of pathogen-specific phages, allowing for identification of bacterial pathogens. We find that information on phage diversity enables identification of the bacteria that produced these phages, including pathovariant strains of Escherichia coli. Phage sequences can likewise be used to distinguish between closely related bacterial species such as Staphylococcus aureus, a frequent pathogen, and coagulase-negative Staphylococcus, a frequent contaminant. Phage cell-free DNA may have utility in studying bacterial infections.
    MeSH term(s) Humans ; Bacteriophages/genetics ; Bacteria/genetics ; Escherichia coli/genetics ; Sepsis
    Language English
    Publishing date 2023-06-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-023-01406-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Regulatory context drives conservation of glycine riboswitch aptamers.

    Crum, Matt / Ram-Mohan, Nikhil / Meyer, Michelle M

    PLoS computational biology

    2019  Volume 15, Issue 12, Page(s) e1007564

    Abstract: In comparison to protein coding sequences, the impact of mutation and natural selection on the sequence and function of non-coding (ncRNA) genes is not well understood. Many ncRNA genes are narrowly distributed to only a few organisms, and appear to be ... ...

    Abstract In comparison to protein coding sequences, the impact of mutation and natural selection on the sequence and function of non-coding (ncRNA) genes is not well understood. Many ncRNA genes are narrowly distributed to only a few organisms, and appear to be rapidly evolving. Compared to protein coding sequences, there are many challenges associated with assessment of ncRNAs that are not well addressed by conventional phylogenetic approaches, including: short sequence length, lack of primary sequence conservation, and the importance of secondary structure for biological function. Riboswitches are structured ncRNAs that directly interact with small molecules to regulate gene expression in bacteria. They typically consist of a ligand-binding domain (aptamer) whose folding changes drive changes in gene expression. The glycine riboswitch is among the most well-studied due to the widespread occurrence of a tandem aptamer arrangement (tandem), wherein two homologous aptamers interact with glycine and each other to regulate gene expression. However, a significant proportion of glycine riboswitches are comprised of single aptamers (singleton). Here we use graph clustering to circumvent the limitations of traditional phylogenetic analysis when studying the relationship between the tandem and singleton glycine aptamers. Graph clustering enables a broader range of pairwise comparison measures to be used to assess aptamer similarity. Using this approach, we show that one aptamer of the tandem glycine riboswitch pair is typically much more highly conserved, and that which aptamer is conserved depends on the regulated gene. Furthermore, our analysis also reveals that singleton aptamers are more similar to either the first or second tandem aptamer, again based on the regulated gene. Taken together, our findings suggest that tandem glycine riboswitches degrade into functional singletons, with the regulated gene(s) dictating which glycine-binding aptamer is conserved.
    MeSH term(s) Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/genetics ; Bacillaceae/classification ; Bacillaceae/genetics ; Computational Biology ; Evolution, Molecular ; Genome, Bacterial ; Glycine/chemistry ; Models, Genetic ; Models, Molecular ; Nucleic Acid Conformation ; Phylogeny ; Riboswitch/genetics ; Vibrionaceae/classification ; Vibrionaceae/genetics
    Chemical Substances Aptamers, Nucleotide ; Riboswitch ; Glycine (TE7660XO1C)
    Language English
    Publishing date 2019-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1007564
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection.

    Ram-Mohan, Nikhil / Thair, Simone A / Litzenburger, Ulrike M / Cogill, Steven / Andini, Nadya / Yang, Xi / Chang, Howard Y / Yang, Samuel

    Life science alliance

    2021  Volume 4, Issue 8

    Abstract: Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid ...

    Abstract Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid in disease recognition. We performed assay for transposase-accessible chromatin (ATAC)-seq of human neutrophils challenged with six toll-like receptor ligands and two organisms; and RNA-seq after
    MeSH term(s) Adult ; Chromatin Immunoprecipitation Sequencing/methods ; Epigenomics ; Escherichia coli/pathogenicity ; Escherichia coli Infections/genetics ; Female ; Gene Expression Regulation ; Humans ; Models, Biological ; Neutrophils/chemistry ; Neutrophils/microbiology ; Promoter Regions, Genetic ; Sepsis/genetics ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Time Factors
    Language English
    Publishing date 2021-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202000976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Erratum for Hashemi et al., "A Novel Platform Using RNA Signatures To Accelerate Antimicrobial Susceptibility Testing in Neisseria gonorrhoeae".

    Hashemi, Marjan M / Ram-Mohan, Nikhil / Yang, Xi / Andini, Nadya / Gessner, Nicholas R / Carroll, Karen C / Wang, Tza-Huei / Yang, Samuel

    Journal of clinical microbiology

    2021  Volume 59, Issue 3

    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.03041-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Association Between SARS-CoV-2 RNAemia and Post-Acute Sequelae of COVID-19.

    Ram-Mohan, Nikhil / Kim, David / Rogers, Angela J / Blish, Catherine A / Nadeau, Kari C / Blomkalns, Andra L / Yang, Samuel

    medRxiv : the preprint server for health sciences

    2021  

    Abstract: Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 75% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent ... ...

    Abstract Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 75% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, initial disease severity, and length of symptoms.
    Language English
    Publishing date 2021-09-07
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.09.03.21262934
    Database MEDical Literature Analysis and Retrieval System OnLINE

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