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Article ; Online: Salivary immunoinflammatory proteins identify children with eosinophilic esophagitis.

Hiremath, Girish / Wang, Yu / Correa, Hernan / Sheng, Quanhu / Rajagopala, Seesandra V

2024

Language	English
Publishing date	2024-01-29
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.16040
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Article ; Online: Mucosal Microbiome Disruption in Acute Laryngeal Injury Following Intubation.

Davis, Ruth J / Shilts, Meghan H / Strickland, Britton A / Rajagopala, Seesandra V / Das, Suman R / Wootten, Christopher T / Gelbard, Alexander

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

2023 Volume 170, Issue 3, Page(s) 977–980

Abstract: The objective of this study was to characterize mucosal microbial shifts in patients with acute laryngeal injury (ALgI) after intubation. This cross-sectional study included 20 patients with ALgI who underwent early endoscopic intervention with tissue ... ...

Abstract	The objective of this study was to characterize mucosal microbial shifts in patients with acute laryngeal injury (ALgI) after intubation. This cross-sectional study included 20 patients with ALgI who underwent early endoscopic intervention with tissue culture, 20 patients with idiopathic subglottic stenosis (iSGS) who underwent tissue culture during the routine endoscopic intervention, and 3 control patients who underwent mucosal swab culture. 70% of the ALgI patients had a positive culture compared to 5% of the iSGS patients and none of the controls. The most identified microbes isolated from ALgI patients included Staphylococcus species in 30% and Streptococcus species in 25%. The high rate of pathologic bacterial infiltration into postintubation laryngeal wounds supports efforts to reduce bacterial colonization of endotracheal tubes and highlights the role of culture-directed antibiotic therapy as a part of early intervention to improve outcomes for patients with ALgI.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Laryngeal Diseases/etiology ; Laryngostenosis/etiology ; Intubation, Intratracheal/adverse effects ; Microbiota
Language	English
Publishing date	2023-11-07
Publishing country	England
Document type	Journal Article
ZDB-ID	392085-9
ISSN	1097-6817 ; 0161-6439 ; 0194-5998
ISSN (online)	1097-6817
ISSN	0161-6439 ; 0194-5998
DOI	10.1002/ohn.580
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Article: Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome.

Rajagopala, Seesandra V / Shilts, Meghan H / Correa, Hernan / Das, Suman R / Choksi, Yash A / Jacobse, Justin / Goettel, Jeremy A / Hiremath, Girish

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG

2023 Volume 28, Issue 6, Page(s) 504–508

Abstract: Objective: Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children ... ...

Abstract	Objective: Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. Methods: Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI-], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. Results: The median (IQR) age of our cohort was 14 years (12-16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI-, the PPI+ had upregulation of 27 genes including the Conclusions: In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.
Language	English
Publishing date	2023-10-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028543-4
ISSN	1551-6776
ISSN	1551-6776
DOI	10.5863/1551-6776-28.6.504
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Article ; Online: Association between Oral Microbiome and Esophageal Diseases: A State-of-the-Art Review.

Bernard, Rachel / Fazili, Irtiqa / Rajagopala, Seesandra V / Das, Suman R / Hiremath, Girish

Digestive diseases (Basel, Switzerland)

2021 Volume 40, Issue 3, Page(s) 345–354

Abstract: Background: Esophageal conditions result in significant morbidity and mortality worldwide. There is growing enthusiasm for discerning the role of microbiome in esophageal diseases. Conceivably, the focus has been on examining the role of local ... ...

Abstract	Background: Esophageal conditions result in significant morbidity and mortality worldwide. There is growing enthusiasm for discerning the role of microbiome in esophageal diseases. Conceivably, the focus has been on examining the role of local microbiome in esophageal diseases although this is somewhat limited by the invasive approach required to sample the esophageal tissue. Given the ease of sampling the oral cavity combined with the advances in genomic techniques, there is immense interest in discovering the role of the oral microbiome in esophageal conditions. Summary: In this review, we aim to discuss the current evidence highlighting the association between the oral microbiome and esophageal diseases. In particular, we have focused on summarizing the alterations in oral microbiome associated with malignant, premalignant, and benign esophageal cancers, inflammatory and infectious conditions, and esophageal dysmotility diseases. Identifying alterations in the oral microbiome is a key to advancing our understanding of the etiopathogenesis and progression of esophageal diseases, promoting novel diagnostics, and laying the foundation for personalized treatment approaches. Key messages: Further studies are needed to unravel the mechanisms by which the oral microbiome influences the development and progression of esophageal diseases, as well as to investigate whether alterations in the oral microbiome can impact the natural history of various esophageal diseases.
MeSH term(s)	Barrett Esophagus/pathology ; Esophageal Diseases/complications ; Esophageal Neoplasms/pathology ; Humans ; Microbiota ; Precancerous Conditions/pathology
Language	English
Publishing date	2021-07-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	632798-9
ISSN	1421-9875 ; 0257-2753
ISSN (online)	1421-9875
ISSN	0257-2753
DOI	10.1159/000517736
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Article ; Online: Upper respiratory tract microbiota dynamics following COVID-19 in adults.

Rosas-Salazar, Christian / Kimura, Kyle S / Shilts, Meghan H / Strickland, Britton A / Freeman, Michael H / Wessinger, Bronson C / Gupta, Veerain / Brown, Hunter M / Boone, Helen H / Rajagopala, Seesandra V / Turner, Justin H / Das, Suman Ranjan

Microbial genomics

2023 Volume 9, Issue 2

Abstract: To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this ...

Abstract	To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this knowledge gap, we used 16S ribosomal RNA gene sequencing to characterize the URT microbiota in 48 adults, including (1) 24 participants with mild-to-moderate COVID-19 who had serial mid-turbinate swabs collected up to 21 days after enrolment and (2) 24 asymptomatic, uninfected controls who had mid-turbinate swabs collected at enrolment only. To compare the URT microbiota between groups in a comprehensive manner, different types of statistical analyses that are frequently employed in microbial ecology were used, including ⍺-diversity, β-diversity and differential abundance analyses. Final statistical models included age, sex and the presence of at least one comorbidity as covariates. The median age of all participants was 34.00 (interquartile range=28.75-46.50) years. In comparison to samples from controls, those from participants with COVID-19 had a lower observed species index at day 21 (linear regression coefficient=-13.30; 95 % CI=-21.72 to -4.88;
MeSH term(s)	Humans ; Adult ; Middle Aged ; COVID-19 ; SARS-CoV-2 ; Microbiota ; Respiratory System
Language	English
Publishing date	2023-02-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2835258-0
ISSN	2057-5858 ; 2057-5858
ISSN (online)	2057-5858
ISSN	2057-5858
DOI	10.1099/mgen.0.000957
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Article ; Online: Mucosal Gene Expression in Response to SARS-CoV-2 Is Associated with Viral Load.

Rajagopala, Seesandra V / Strickland, Britton A / Pakala, Suman B / Kimura, Kyle S / Shilts, Meghan H / Rosas-Salazar, Christian / Brown, Hunter M / Freeman, Michael H / Wessinger, Bronson C / Gupta, Veerain / Phillips, Elizabeth / Mallal, Simon A / Turner, Justin H / Das, Suman R

Journal of virology

2023 Volume 97, Issue 2, Page(s) e0147822

Abstract: Little is known about the relationships between symptomatic early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 ... ...

Abstract	Little is known about the relationships between symptomatic early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate coronavirus disease 19 (COVID-19). We measured SARS-CoV-2 viral load using reverse transcription-quantitative PCR (RT-qPCR). We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 95% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited codetection of other respiratory viruses, with the human Rhinovirus C being identified in 4 (6%) samples. This limited codetection of other respiratory viral pathogens may be due to the implementation of public health measures, like social distancing and masking practices. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusting for age, sex, and race. Interestingly, the expression levels of most of these genes plateaued at a cycle threshold (
MeSH term(s)	Adult ; Humans ; Chemokines/physiology ; COVID-19/immunology ; COVID-19/virology ; Gene Expression/immunology ; Immunity, Mucosal/immunology ; Interferons/physiology ; SARS-CoV-2/genetics ; Viral Load ; Respiratory Mucosa/immunology ; Respiratory Mucosa/virology
Chemical Substances	Chemokines ; Interferons (9008-11-1)
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01478-22
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Article ; Online: From

Lykins, Joseph / Moschitto, Matthew J / Zhou, Ying / Filippova, Ekaterina V / Le, Hoang V / Tomita, Tadakimi / Fox, Barbara A / Bzik, David J / Su, Chunlei / Rajagopala, Seesandra V / Flores, Kristin / Spano, Furio / Woods, Stuart / Roberts, Craig W / Hua, Cong / El Bissati, Kamal / Wheeler, Kelsey M / Dovgin, Sarah / Muench, Stephen P /

McPhillie, Martin / Fishwick, Colin W G / Anderson, Wayne F / Lee, Patricia J / Hickman, Mark / Weiss, Louis M / Dubey, Jitender P / Lorenzi, Hernan A / Silverman, Richard B / McLeod, Rima L

iScience

2023 Volume 27, Issue 1, Page(s) 108477

Abstract: Toxoplasma ... ...

Abstract	Toxoplasma gondii
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108477
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Article ; Online: Species-specific transcriptomic changes upon respiratory syncytial virus infection in cotton rats.

Strickland, Britton A / Rajagopala, Seesandra V / Kamali, Arash / Shilts, Meghan H / Pakala, Suman B / Boukhvalova, Marina S / Yooseph, Shibu / Blanco, Jorge C G / Das, Suman R

Scientific reports

2022 Volume 12, Issue 1, Page(s) 16579

Abstract: The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene ... ...

Abstract	The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a comprehensive transcriptome from multiple tissues of two species of cotton rats that are commonly used as animal models (Sigmodon fulviventer and Sigmodon hispidus), and to compare and contrast gene expression changes and immune responses to RSV infection between the two species. Transcriptomes were assembled from lung, spleen, kidney, heart, and intestines for each species with a contig N50 > 1600. Annotation of contigs generated nearly 120,000 gene annotations for each species. The transcriptomes of S. fulviventer and S. hispidus were then used to assess immune response to RSV infection. We identified 238 unique genes that are significantly differentially expressed, including several genes implicated in RSV infection (e.g., Mx2, I27L2, LY6E, Viperin, Keratin 6A, ISG15, CXCL10, CXCL11, IRF9) as well as novel genes that have not previously described in RSV research (LG3BP, SYWC, ABEC1, IIGP1, CREB1). This study presents two comprehensive transcriptome references as resources for future gene expression analysis studies in the cotton rat model, as well as provides gene sequences for mechanistic characterization of molecular pathways. Overall, our results provide generalizable insights into the effect of host genetics on host-virus interactions, as well as identify new host therapeutic targets for RSV treatment and prevention.
MeSH term(s)	Animals ; Antibodies, Viral ; Disease Models, Animal ; Keratin-6/genetics ; Lung ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Virus, Human/genetics ; Sigmodontinae ; Transcriptome
Chemical Substances	Antibodies, Viral ; Keratin-6
Language	English
Publishing date	2022-10-04
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-19810-4
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Article: Analysis of protein-protein interactions using array-based yeast two-hybrid screens.

Rajagopala, Seesandra V / Uetz, Peter

Methods in molecular biology (Clifton, N.J.)

2013 Volume 548, Page(s) 223–245

Abstract: The yeast two-hybrid system (Y2H) is a powerful tool to identify protein-protein interactions. Here we describe array-based two-hybrid methods that use defined libraries of open reading frames (ORFs) as opposed to random genomic or cDNA libraries. The ... ...

Abstract	The yeast two-hybrid system (Y2H) is a powerful tool to identify protein-protein interactions. Here we describe array-based two-hybrid methods that use defined libraries of open reading frames (ORFs) as opposed to random genomic or cDNA libraries. The array-based Y2H system is well suited for interactome studies of existing ORFeomes or subsets thereof, preferentially in a recombination-based cloning system. Array-based Y2H screens efficiently reduce false positives by using built-in controls, retesting, and evaluation of background activation. Hands-on time and the amount of used resources grow exponentially with the number of tested proteins; this is a disadvantage for large genome sizes. For large genomes, random library screen may be more efficient in terms of time and resources, but not as comprehensive as array screens, and they require an efficient sequencing facility. However, large array screens require some extent of automation although they can be carried out manually on smaller scales. Future-generation Y2H plasmid constructs including tightly regulated expression systems and features that facilitate biochemical characterization will provide more efficient and powerful tools to identify interacting proteins.
MeSH term(s)	Genes, Reporter ; Genome, Fungal ; Genomic Library ; Open Reading Frames ; Plasmids/genetics ; Protein Array Analysis/methods ; Protein Interaction Mapping/methods ; Proteome ; Proteomics/methods ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transformation, Genetic ; Two-Hybrid System Techniques
Chemical Substances	Proteome ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2013-06-24
Publishing country	United States
Document type	Journal Article
ISSN	1064-3745
ISSN	1064-3745
DOI	10.1007/978-1-59745-540-4_13
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Article ; Online: From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma

Joseph Lykins / Matthew J. Moschitto / Ying Zhou / Ekaterina V. Filippova / Hoang V. Le / Tadakimi Tomita / Barbara A. Fox / David J. Bzik / Chunlei Su / Seesandra V. Rajagopala / Kristin Flores / Furio Spano / Stuart Woods / Craig W. Roberts / Cong Hua / Kamal El Bissati / Kelsey M. Wheeler / Sarah Dovgin / Stephen P. Muench /

Martin McPhillie / Colin W.G. Fishwick / Wayne F. Anderson / Patricia J. Lee / Mark Hickman / Louis M. Weiss / Jitender P. Dubey / Hernan A. Lorenzi / Richard B. Silverman / Rima L. McLeod

iScience, Vol 27, Iss 1, Pp 108477- (2024)

1481

Abstract: Summary: Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å ... ...

Abstract	Summary: Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat’s oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with “Rosetta stone”-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite’s capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease.
Keywords	Parasitology ; Cell biology ; Science ; Q
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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