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2. Date palm transcriptome analysis provides new insights on changes in response to high salt stress of colonized roots with the endophytic fungus Piriformospora indica.

Author

Ahmad, Manzoor, Aziz, Mughair Abdul, Sabeem, Miloofer, Kutty, M. Sangeeta, Sivasankaran, Sathesh K., Brini, Faical, Ting Ting Xiao, Blilou, Ikram, and Masmoudi, Khaled

Subjects
DATE palm, GENE expression, PRINCIPAL components analysis, ATP-binding cassette transporters, ABSCISIC acid
Abstract

Salinity is a significant threat that causes considerable yield losses in date palm. The root endophytic fungus Piriformospora indica has proven effective in providing salt stress tolerance to host plants. However, the underlying molecular mechanism facilitating the date palm's response to P. indica inoculation, and its involvement in the salt stress tolerance, remains unknown. In this study, the colonization of P. indica on date palm seedlings exposed to saline conditions was observed through confocal microscopy, and its impact on gene expressions was evaluated using the transcriptomic analysis. Our findings show that P. indica colonization reinforced the cortical cells, prevented them from plasmolysis and cell death under salinity. The RNAseq analysis produced clean reads ranging from 62,040,451 to 3,652,095 across the treatment groups, successfully assembling into 30,600 annotated genes. Out of them, the number of differentially expressed genes (DEGs) varied across the treatments: i.e., 2523, 2031, and 1936 DEGs were upregulated, while 2323, 959, and 3546 were downregulated in Salt, Fungi, and Fungi+Salt groups, respectively. Furthermore, principal component analysis based on transcriptome profiles revealed discrete clustering of samples from different treatment groups. KEGG and GO pathways enrichment analysis highlighted variation in the number and types of enriched pathways among the treatments. Our study indicated variations in gene expression related to plant hormone biosynthesis and signal transduction (auxin, abscisic acid, gibberellin, and ethylene), ABC transporters, sodium/hydrogen exchanger, cation HKT transporter, transcription factors such as WRKY and MYBs, and the plant immune system (lipoxygenase and jasmonate) of the date palm seedlings. By characterizing the transcriptome of date palm roots under salt stress and with colonization of P. indica, the present findings provide valuable perspectives on the molecular mechanisms responsible for inducing salinity stress tolerance in plants. [ABSTRACT FROM AUTHOR]

Published
2024
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11. The transcriptional landscape and small RNAs of Salmonella enterica serovar Typhimurium

Author

Kröger, Carsten, Dillon, Shane C., Cameron, Andrew D. S., Papenfort, Kai, Sivasankaran, Sathesh K., Hokamp, Karsten, Chao, Yanjie, Sittka, Alexandra, Hébrard, Magali, Händler, Kristian, Colgan, Aoife, Leekitcharoenphon, Pimlapas, Langridge, Gemma C., Lohan, Amanda J., Loftus, Brendan, Lucchini, Sacha, Ussery, David W., Dorman, Charles J., Thomson, Nicholas R., Vogel, Jörg, and Hinton, Jay C. D.

Published
2012

14. Regional epithelial cell diversity in the small intestine of pigs.

Author

Wiarda, Jayne E, Becker, Sage R, Sivasankaran, Sathesh K, and Loving, Crystal L

Subjects
EPITHELIAL cells, GENE expression, SMALL intestine, RNA analysis, ENTEROCYTES, RNA sequencing
Abstract

Understanding regional distribution and specialization of small intestinal epithelial cells is crucial for developing methods to control appetite, stress, and nutrient uptake in swine. To establish a better understanding of specific epithelial cells found across different regions of the small intestine in pigs, we utilized single-cell RNA sequencing (scRNA-seq) to recover and analyze epithelial cells from duodenum, jejunum, and ileum. Cells identified included crypt cells, enterocytes, BEST4 enterocytes, goblet cells, and enteroendocrine (EE) cells. EE cells were divided into two subsets based on the level of expression of the EE lineage commitment gene, NEUROD1. NEUROD1 hi EE cells had minimal expression of hormone-encoding genes and were dissimilar to EE cells in humans and mice, indicating a subset of EE cells unique to pigs. Recently discovered BEST4 enterocytes were detected in both crypts and villi throughout the small intestine via in situ staining, unlike in humans, where BEST4 enterocytes are found only in small intestinal villi. Proximal-to-distal gradients of expression were noted for hormone-encoding genes in EE cells and nutrient transport genes in enterocytes via scRNA-seq, demonstrating regional specialization. Regional gene expression in EE cells and enterocytes was validated via quantitative PCR (qPCR) analysis of RNA isolated from epithelial cells of different small intestinal locations. Though many genes had similar patterns of regional expression when assessed by qPCR of total epithelial cells, some regional expression was only detected via scRNA-seq, highlighting advantages of scRNA-seq to deconvolute cell type-specific regional gene expression when compared to analysis of bulk samples. Overall, results provide new information on regional localization and transcriptional profiles of epithelial cells in the pig small intestine. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Analysis of the Oxidative Stress Regulon Identifies soxS as a Genetic Target for Resistance Reversal in Multidrug-Resistant Klebsiella pneumoniae

Author

Anes, João, primary, Dever, Katherine, additional, Eshwar, Athmanya, additional, Nguyen, Scott, additional, Cao, Yu, additional, Sivasankaran, Sathesh K., additional, Sakalauskaitė, Sandra, additional, Lehner, Angelika, additional, Devineau, Stéphanie, additional, Daugelavičius, Rimantas, additional, Stephan, Roger, additional, Fanning, Séamus, additional, and Srikumar, Shabarinath, additional

Published
2021
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20. Analysis of the Oxidative Stress Regulon Identifies soxS as a Genetic Target for Resistance Reversal in Multidrug-Resistant Klebsiella pneumoniae

Author

Brown, Eric, Bush, Karen, Brown, E ( Eric ), Bush, K ( Karen ), Anes, João; https://orcid.org/0000-0002-6588-7162, Dever, Katherine; https://orcid.org/0000-0002-9861-9148, Eshwar, Athmanya; https://orcid.org/0000-0002-9524-2517, Nguyen, Scott; https://orcid.org/0000-0001-6498-2232, Cao, Yu; https://orcid.org/0000-0002-0829-2701, Sivasankaran, Sathesh K; https://orcid.org/0000-0003-3037-6001, Sakalauskaitė, Sandra; https://orcid.org/0000-0002-9261-4805, Lehner, Angelika; https://orcid.org/0000-0003-1863-5090, Devineau, Stéphanie; https://orcid.org/0000-0002-1133-5223, Daugelavičius, Rimantas; https://orcid.org/0000-0001-9721-6200, Stephan, Roger; https://orcid.org/0000-0003-1002-4762, Fanning, Séamus; https://orcid.org/0000-0002-1922-8836, Srikumar, Shabarinath; https://orcid.org/0000-0003-3775-2831, Brown, Eric, Bush, Karen, Brown, E ( Eric ), Bush, K ( Karen ), Anes, João; https://orcid.org/0000-0002-6588-7162, Dever, Katherine; https://orcid.org/0000-0002-9861-9148, Eshwar, Athmanya; https://orcid.org/0000-0002-9524-2517, Nguyen, Scott; https://orcid.org/0000-0001-6498-2232, Cao, Yu; https://orcid.org/0000-0002-0829-2701, Sivasankaran, Sathesh K; https://orcid.org/0000-0003-3037-6001, Sakalauskaitė, Sandra; https://orcid.org/0000-0002-9261-4805, Lehner, Angelika; https://orcid.org/0000-0003-1863-5090, Devineau, Stéphanie; https://orcid.org/0000-0002-1133-5223, Daugelavičius, Rimantas; https://orcid.org/0000-0001-9721-6200, Stephan, Roger; https://orcid.org/0000-0003-1002-4762, Fanning, Séamus; https://orcid.org/0000-0002-1922-8836, and Srikumar, Shabarinath; https://orcid.org/0000-0003-3775-2831

Abstract

In bacteria, the defense system deployed to counter oxidative stress is orchestrated by three transcriptional factors, SoxS, SoxR, and OxyR. Although the regulon that these factors control is known in many bacteria, similar data are not available for Klebsiella pneumoniae. To address this data gap, oxidative stress was artificially induced in K. pneumoniae MGH78578 using paraquat and the corresponding oxidative stress regulon recorded using transcriptome sequencing (RNA-seq). The soxS gene was significantly induced during oxidative stress, and a knockout mutant was constructed to explore its functionality. The wild type and mutant were grown in the presence of paraquat and subjected to RNA-seq to elucidate the soxS regulon in K. pneumoniae MGH78578. Genes that are commonly regulated both in the oxidative stress and soxS regulons were identified and denoted as the oxidative SoxS regulon; these included a group of genes specifically regulated by SoxS. Efflux pump-encoding genes and global regulators were identified as part of this regulon. Consequently, the isogenic soxS mutant was found to exhibit a reduction in the minimum bactericidal concentration against tetracycline compared to that of the wild type. Impaired efflux activity, allowing tetracycline to be accumulated in the cytoplasm to bactericidal levels, was further evaluated using a tetraphenylphosphonium (TPP+) accumulation assay. The soxS mutant was also susceptible to tetracycline in vivo in a zebrafish embryo model. We conclude that the soxS gene could be considered a genetic target against which an inhibitor could be developed and used in combinatorial therapy to combat infections associated with multidrug-resistant K. pneumoniae. IMPORTANCE Antimicrobial resistance is a global health challenge. Few new antibiotics have been developed for use over the years, and preserving the efficacy of existing compounds is an important step to protect public health. This paper describes a study that examines the effec

Published
2021

24. The Role of Salmonella Genomic Island 4 in Metal Tolerance of Salmonella enterica Serovar I 4,[5],12:i:- Pork Outbreak Isolate USDA15WA-1

Author

Bearson, Bradley L., primary, Trachsel, Julian M., additional, Shippy, Daniel C., additional, Sivasankaran, Sathesh K., additional, Kerr, Brian J., additional, Loving, Crystal L., additional, Brunelle, Brian W., additional, Curry, Shelby M., additional, Gabler, Nicholas K., additional, and Bearson, Shawn M. D., additional

Published
2020
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26. Analysis of the oxidative stress regulon identifiessoxSas a genetic target for resistance reversal in multi-drug resistantKlebsiella pneumoniae

Author

Anes, João, primary, Dever, Katherine, additional, Eshwar, Athmanya, additional, Nguyen, Scott, additional, Cao, Yu, additional, Sivasankaran, Sathesh K, additional, Sakalauskaitė, Sandra, additional, Lehner, Angelika, additional, Devineau, Stéphanie, additional, Daugelavičius, Rimantas, additional, Fanning, Séamus, additional, and Srikumar, Shabarinath, additional

Published
2020
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27. Immune and Inflammatory Pathways Implicated by Whole Blood Transcriptomic Analysis in a Diverse Ancestry Alzheimer’s Disease Cohort

Author

Griswold, Anthony J., primary, Sivasankaran, Sathesh K., additional, Van Booven, Derek, additional, Gardner, Olivia K., additional, Rajabli, Farid, additional, Whitehead, Patrice L., additional, Hamilton-Nelson, Kara L., additional, Adams, Larry D., additional, Scott, Aja M., additional, Hofmann, Natalia K., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Bush, William S., additional, Martin, Eden R., additional, Byrd, Goldie S., additional, Haines, Jonathan L., additional, Pericak-Vance, Margaret A., additional, and Beecham, Gary W., additional

Published
2020
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28. Complete Genome Sequence of Multidrug-Resistant Salmonella enterica Serovar I 4,[5],12:i:− 2015 U.S. Pork Outbreak Isolate USDA15WA-1

Author

Bearson, Bradley L., primary, Trachsel, Julian M., additional, Holman, Devin B., additional, Brunelle, Brian W., additional, Sivasankaran, Sathesh K., additional, Simmons, Mustafa, additional, Wasilenko, Jamie, additional, Tillman, Glenn, additional, Johnston, John J., additional, and Bearson, Shawn M. D., additional

Published
2019
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30. RNA Sequencing-Based Transcriptional Overview of Xerotolerance in Cronobacter sakazakii SP291

Author

Srikumar, Shabarinath, primary, Cao, Yu, additional, Yan, Qiongqiong, additional, Van Hoorde, Koenraad, additional, Nguyen, Scott, additional, Cooney, Shane, additional, Gopinath, Gopal R., additional, Tall, Ben D., additional, Sivasankaran, Sathesh K., additional, Lehner, Angelika, additional, Stephan, Roger, additional, and Fanning, Séamus, additional

Published
2019
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31. The primary transcriptome, small RNAs and regulation of antimicrobial resistance in Acinetobacter baumannii ATCC 17978

Author

Kröger, Carsten, primary, MacKenzie, Keith D, additional, Alshabib, Ebtihal Y, additional, Kirzinger, Morgan W B, additional, Suchan, Danae M, additional, Chao, Tzu-Chiao, additional, Akulova, Valentyna, additional, Miranda-CasoLuengo, Aleksandra A, additional, Monzon, Vivian A, additional, Conway, Tyrrell, additional, Sivasankaran, Sathesh K, additional, Hinton, Jay C D, additional, Hokamp, Karsten, additional, and Cameron, Andrew D S, additional

Published
2018
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32. P1‐144: TRANSCRIPTOMIC ANALYSIS OF WHOLE BLOOD IN AFRICAN AMERICAN AND NON‐HISPANIC WHITE ALZHEIMER DISEASE CASES AND CONTROLS

Author

Griswold, Anthony J., primary, Sivasankaran, Sathesh K., additional, Gardner, Olivia K., additional, Rajabli, Farid, additional, Hamilton-Nelson, Kara L., additional, Rolati, Sophie, additional, Hofmann, Natalia K., additional, Whitehead, Patrice L., additional, Adams, Larry D., additional, Byrd, Goldie S., additional, Martin, Eden R., additional, Cuccaro, Michael L., additional, Bush, William S., additional, Haines, Jonathan L., additional, Vance, Jeffery M., additional, Beecham, Gary W., additional, and Pericak-Vance, Margaret A., additional

Published
2018
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33. Modulation of Transcriptomic Changes in Alzheimer Disease by Ethnicity (S5.004)

Author

Sivasankaran, Sathesh K., primary, Griswold, Anthony J., additional, Gardner, Olivia K., additional, Rajabli, Farid, additional, Kunkle, Brian, additional, Hamilton, Kara, additional, Jaworski, James, additional, Bush, William S., additional, Martin, Eden R., additional, Beecham, Gary W., additional, Byrd, Goldie S., additional, Haines, Jonathan L., additional, and Pericak-Vance, Margaret A., additional

Published
2018
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34. The primary transcriptome, small RNAs, and regulation of antimicrobial resistance inAcinetobacter baumannii

Author

Kröger, Carsten, primary, MacKenzie, Keith D., additional, Al-Shabib, Ebtihal Y., additional, Kirzinger, Morgan W. B., additional, Suchan, Danae M., additional, Chao, Tzu-Chiao, additional, Akulova, Valentyna, additional, Miranda-CasoLuengo, Alesksandra A., additional, Monzon, Vivian A., additional, Conway, Tyrrell, additional, Sivasankaran, Sathesh K., additional, Hinton, Jay C. D., additional, Hokamp, Karsten, additional, and Cameron, Andrew D. S., additional

Published
2017
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35. RNA-seq Brings New Insights to the Intra-Macrophage Transcriptome of Salmonella Typhimurium

Author

Srikumar, Shabarinath, Kröger, Carsten, Hébrard, Magali, Colgan, Aoife, Owen, Siân V., Sivasankaran, Sathesh K., Cameron, Andrew D. S., Hokamp, Karsten, and Hinton, Jay C. D.

Subjects
Salmonella typhimurium, Genomic Islands, Virulence, Salmonella Vaccines, QH301-705.5, Macrophages, High-Throughput Nucleotide Sequencing, Gene Expression Regulation, Bacterial, RC581-607, QR, RNA, Bacterial, Bacterial Proteins, Genes, Bacterial, Immunologic diseases. Allergy, Biology (General), Transcriptome, Research Article
Abstract

Salmonella enterica serovar Typhimurium is arguably the world’s best-understood bacterial pathogen. However, crucial details about the genetic programs used by the bacterium to survive and replicate in macrophages have remained obscure because of the challenge of studying gene expression of intracellular pathogens during infection. Here, we report the use of deep sequencing (RNA-seq) to reveal the transcriptional architecture and gene activity of Salmonella during infection of murine macrophages, providing new insights into the strategies used by the pathogen to survive in a bactericidal immune cell. We characterized 3583 transcriptional start sites that are active within macrophages, and highlight 11 of these as candidates for the delivery of heterologous antigens from Salmonella vaccine strains. A majority (88%) of the 280 S. Typhimurium sRNAs were expressed inside macrophages, and SPI13 and SPI2 were the most highly expressed pathogenicity islands. We identified 31 S. Typhimurium genes that were strongly up-regulated inside macrophages but expressed at very low levels during in vitro growth. The SalComMac online resource allows the visualisation of every transcript expressed during bacterial replication within mammalian cells. This primary transcriptome of intra-macrophage S.-Typhimurium describes the transcriptional start sites and the transcripts responsible for virulence traits, and catalogues the sRNAs that may play a role in the regulation of gene expression during infection., Author Summary The burden of Salmonellosis remains unacceptably high throughout the world and control measures have had limited success. Because Salmonella bacteria can be transmitted from the wider environment to animals and humans, the bacteria encounter diverse environments that include food, water, plant surfaces and the extracellular and intracellular phases of infection of eukaryotic hosts. An intricate transcriptional network has evolved to respond to a variety of environmental signals and control the “right time/ right place” expression of virulence genes. To understand how transcription is rewired during intracellular infection, we determined the primary transcriptome of Salmonella enterica serovar Typhimurium within murine macrophages. We report the coding genes, sRNAs and transcriptional start sites that are expressed within macrophages at 8 hours after infection, and use these to infer gene function. We identified gene promoters that are specifically expressed within macrophages and could drive the intracellular delivery of antigens by S. Typhimurium vaccine strains. These data contribute to our understanding of the mechanisms used by Salmonella to regulate virulence gene expression whilst replicating inside mammalian cells.

Published
2015

37. TRANSCRIPTOMIC ANALYSIS OF WHOLE BLOOD IN AFRICAN AMERICAN AND NON-HISPANIC WHITE ALZHEIMER DISEASE CASES AND CONTROLS

Author

Griswold, Anthony J., Sivasankaran, Sathesh K., Gardner, Olivia K., Rajabli, Farid, Hamilton-Nelson, Kara L., Rolati, Sophie, Hofmann, Natalia K., Whitehead, Patrice L., Adams, Larry D., Byrd, Goldie S., Martin, Eden R., Cuccaro, Michael L., Bush, William S., Haines, Jonathan L., Vance, Jeffery M., Beecham, Gary W., and Pericak-Vance, Margaret A.

Published
2018
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41. A Model System for Studying the Transcriptomic and Physiological Changes Associated with Mammalian Host-Adaptation by Leptospira interrogans Serovar Copenhageni.

Author

Caimano, Melissa J., Sivasankaran, Sathesh K., Allard, Anna, Hurley, Daniel, Hokamp, Karsten, Grassmann, André A., Hinton, Jay C. D., and Nally, Jarlath E.

Subjects
*LEPTOSPIROSIS, *SPIROCHETES, *LEPTOSPIRA, *INFECTIOUS disease transmission, *GENE expression in viruses
Abstract

Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with >10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil's) disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of “core” housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host-adaption, selection of targets for mutagenesis, and the identification of previously unrecognized virulence determinants. [ABSTRACT FROM AUTHOR]

Published
2014
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42. Analysis of the Oxidative Stress Regulon Identifies soxSas a Genetic Target for Resistance Reversal in Multidrug-Resistant Klebsiella pneumoniae

Author

Anes, João, Dever, Katherine, Eshwar, Athmanya, Nguyen, Scott, Cao, Yu, Sivasankaran, Sathesh K., Sakalauskaitė, Sandra, Lehner, Angelika, Devineau, Stéphanie, Daugelavičius, Rimantas, Stephan, Roger, Fanning, Séamus, and Srikumar, Shabarinath

Abstract

Antimicrobial resistance is a global health challenge. Few new antibiotics have been developed for use over the years, and preserving the efficacy of existing compounds is an important step to protect public health. This paper describes a study that examines the effects of exogenously induced oxidative stress on K. pneumoniaeand uncovers a target that could be useful to harness as a strategy to mitigate resistance.

Published
2021
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