In vivo expression of salmonella enterica serotype typhi genes in the blood of patients with typhoid fever in Bangladesh

Alaullah Sheikh, Richelle C. Charles, Nusrat Sharmeen, Sean M. Rollins, Jason B. Harris, Md Saruar Bhuiyan, Mohammad Arifuzzaman, Farhana Khanam, Archana Bukka, Anuj Kalsy, Steffen Porwollik, Daniel T. Leung, W Abdullah Brooks, Regina C. LaRocque, Elizabeth L. Hohmann, Alejandro Cravioto, Tanya Logvinenko, Stephen B. Calderwood, Michael McClelland, James E. GrahamFirdausi Qadri, Edward T. Ryan

Research output: Contribution to journalArticle

Abstract

Background: Salmonella enterica serotype Typhi is the cause of typhoid fever. It is a human-restricted pathogen, and few data exist on S. Typhi gene expression in humans. Methodology/Principal Findings: We applied an RNA capture and amplification technique, Selective Capture of Transcribed Sequences (SCOTS), and microarray hybridization to identify S. Typhi transcripts expressed in the blood of five humans infected with S. Typhi in Bangladesh. In total, we detected the expression of mRNAs for 2,046 S. Typhi genes (44% of the S. Typhi genome) in human blood; expression of 912 genes was detected in all 5 patients, and expression of 1,100 genes was detected in 4 or more patients. Identified transcripts were associated with the virulence-associated PhoP regulon, Salmonella pathogenicity islands, the use of alternative carbon and energy sources, synthesis and transport of iron, thiamine, and biotin, and resistance to antimicrobial peptides and oxidative stress. The most highly represented group were genes currently annotated as encoding proteins designated as hypothetical, unknown, or unclassified. Of the 2,046 detected transcripts, 1,320 (29% of the S. Typhi genome) had significantly different levels of detection in human blood compared to in vitro cultures; detection of 141 transcripts was significantly different in all 5 patients, and detection of 331 transcripts varied in at least 4 patients. These mRNAs encode proteins of unknown function, those involved in energy metabolism, transport and binding, cell envelope, cellular processes, and pathogenesis. We confirmed increased expression of a subset of identified mRNAs by quantitative-PCR. Conclusions/Significance: We report the first characterization of bacterial transcriptional profiles in the blood of patients with typhoid fever. S. Typhi is an important global pathogen whose restricted host range has greatly inhibited laboratory studies. Our results suggest that S. Typhi uses a largely uncharacterized genetic repertoire to survive within cells and utilize alternate energy sources during infection.

Original languageEnglish (US)
Article numbere1419
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Salmonella enterica
Bangladesh
Typhoid Fever
Genes
Messenger RNA
Nucleic Acid Amplification Techniques
Genomic Islands
Gene Expression
Regulon
Host Specificity
Thiamine
Human Genome
Biotin
Salmonella
Energy Metabolism
Virulence
Proteins
Oxidative Stress
Carbon
Iron

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Sheikh, A., Charles, R. C., Sharmeen, N., Rollins, S. M., Harris, J. B., Bhuiyan, M. S., ... Ryan, E. T. (2011). In vivo expression of salmonella enterica serotype typhi genes in the blood of patients with typhoid fever in Bangladesh. PLoS Neglected Tropical Diseases, 5(12), [e1419]. https://doi.org/10.1371/journal.pntd.0001419

In vivo expression of salmonella enterica serotype typhi genes in the blood of patients with typhoid fever in Bangladesh. / Sheikh, Alaullah; Charles, Richelle C.; Sharmeen, Nusrat; Rollins, Sean M.; Harris, Jason B.; Bhuiyan, Md Saruar; Arifuzzaman, Mohammad; Khanam, Farhana; Bukka, Archana; Kalsy, Anuj; Porwollik, Steffen; Leung, Daniel T.; Brooks, W Abdullah; LaRocque, Regina C.; Hohmann, Elizabeth L.; Cravioto, Alejandro; Logvinenko, Tanya; Calderwood, Stephen B.; McClelland, Michael; Graham, James E.; Qadri, Firdausi; Ryan, Edward T.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 12, e1419, 12.2011.

Research output: Contribution to journalArticle

Sheikh, A, Charles, RC, Sharmeen, N, Rollins, SM, Harris, JB, Bhuiyan, MS, Arifuzzaman, M, Khanam, F, Bukka, A, Kalsy, A, Porwollik, S, Leung, DT, Brooks, WA, LaRocque, RC, Hohmann, EL, Cravioto, A, Logvinenko, T, Calderwood, SB, McClelland, M, Graham, JE, Qadri, F & Ryan, ET 2011, 'In vivo expression of salmonella enterica serotype typhi genes in the blood of patients with typhoid fever in Bangladesh', PLoS Neglected Tropical Diseases, vol. 5, no. 12, e1419. https://doi.org/10.1371/journal.pntd.0001419
Sheikh, Alaullah ; Charles, Richelle C. ; Sharmeen, Nusrat ; Rollins, Sean M. ; Harris, Jason B. ; Bhuiyan, Md Saruar ; Arifuzzaman, Mohammad ; Khanam, Farhana ; Bukka, Archana ; Kalsy, Anuj ; Porwollik, Steffen ; Leung, Daniel T. ; Brooks, W Abdullah ; LaRocque, Regina C. ; Hohmann, Elizabeth L. ; Cravioto, Alejandro ; Logvinenko, Tanya ; Calderwood, Stephen B. ; McClelland, Michael ; Graham, James E. ; Qadri, Firdausi ; Ryan, Edward T. / In vivo expression of salmonella enterica serotype typhi genes in the blood of patients with typhoid fever in Bangladesh. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 12.
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abstract = "Background: Salmonella enterica serotype Typhi is the cause of typhoid fever. It is a human-restricted pathogen, and few data exist on S. Typhi gene expression in humans. Methodology/Principal Findings: We applied an RNA capture and amplification technique, Selective Capture of Transcribed Sequences (SCOTS), and microarray hybridization to identify S. Typhi transcripts expressed in the blood of five humans infected with S. Typhi in Bangladesh. In total, we detected the expression of mRNAs for 2,046 S. Typhi genes (44{\%} of the S. Typhi genome) in human blood; expression of 912 genes was detected in all 5 patients, and expression of 1,100 genes was detected in 4 or more patients. Identified transcripts were associated with the virulence-associated PhoP regulon, Salmonella pathogenicity islands, the use of alternative carbon and energy sources, synthesis and transport of iron, thiamine, and biotin, and resistance to antimicrobial peptides and oxidative stress. The most highly represented group were genes currently annotated as encoding proteins designated as hypothetical, unknown, or unclassified. Of the 2,046 detected transcripts, 1,320 (29{\%} of the S. Typhi genome) had significantly different levels of detection in human blood compared to in vitro cultures; detection of 141 transcripts was significantly different in all 5 patients, and detection of 331 transcripts varied in at least 4 patients. These mRNAs encode proteins of unknown function, those involved in energy metabolism, transport and binding, cell envelope, cellular processes, and pathogenesis. We confirmed increased expression of a subset of identified mRNAs by quantitative-PCR. Conclusions/Significance: We report the first characterization of bacterial transcriptional profiles in the blood of patients with typhoid fever. S. Typhi is an important global pathogen whose restricted host range has greatly inhibited laboratory studies. Our results suggest that S. Typhi uses a largely uncharacterized genetic repertoire to survive within cells and utilize alternate energy sources during infection.",
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T1 - In vivo expression of salmonella enterica serotype typhi genes in the blood of patients with typhoid fever in Bangladesh

AU - Sheikh, Alaullah

AU - Charles, Richelle C.

AU - Sharmeen, Nusrat

AU - Rollins, Sean M.

AU - Harris, Jason B.

AU - Bhuiyan, Md Saruar

AU - Arifuzzaman, Mohammad

AU - Khanam, Farhana

AU - Bukka, Archana

AU - Kalsy, Anuj

AU - Porwollik, Steffen

AU - Leung, Daniel T.

AU - Brooks, W Abdullah

AU - LaRocque, Regina C.

AU - Hohmann, Elizabeth L.

AU - Cravioto, Alejandro

AU - Logvinenko, Tanya

AU - Calderwood, Stephen B.

AU - McClelland, Michael

AU - Graham, James E.

AU - Qadri, Firdausi

AU - Ryan, Edward T.

PY - 2011/12

Y1 - 2011/12

N2 - Background: Salmonella enterica serotype Typhi is the cause of typhoid fever. It is a human-restricted pathogen, and few data exist on S. Typhi gene expression in humans. Methodology/Principal Findings: We applied an RNA capture and amplification technique, Selective Capture of Transcribed Sequences (SCOTS), and microarray hybridization to identify S. Typhi transcripts expressed in the blood of five humans infected with S. Typhi in Bangladesh. In total, we detected the expression of mRNAs for 2,046 S. Typhi genes (44% of the S. Typhi genome) in human blood; expression of 912 genes was detected in all 5 patients, and expression of 1,100 genes was detected in 4 or more patients. Identified transcripts were associated with the virulence-associated PhoP regulon, Salmonella pathogenicity islands, the use of alternative carbon and energy sources, synthesis and transport of iron, thiamine, and biotin, and resistance to antimicrobial peptides and oxidative stress. The most highly represented group were genes currently annotated as encoding proteins designated as hypothetical, unknown, or unclassified. Of the 2,046 detected transcripts, 1,320 (29% of the S. Typhi genome) had significantly different levels of detection in human blood compared to in vitro cultures; detection of 141 transcripts was significantly different in all 5 patients, and detection of 331 transcripts varied in at least 4 patients. These mRNAs encode proteins of unknown function, those involved in energy metabolism, transport and binding, cell envelope, cellular processes, and pathogenesis. We confirmed increased expression of a subset of identified mRNAs by quantitative-PCR. Conclusions/Significance: We report the first characterization of bacterial transcriptional profiles in the blood of patients with typhoid fever. S. Typhi is an important global pathogen whose restricted host range has greatly inhibited laboratory studies. Our results suggest that S. Typhi uses a largely uncharacterized genetic repertoire to survive within cells and utilize alternate energy sources during infection.

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