Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein

Tae Jong Kim, Sadhana Chauhan, Vladimir Motin, Ee Been Goh, Michèle M. Igo, Glenn M. Young

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Horizontal gene transfer events followed by proper regulatory integration of a gene drive rapid evolution of bacterial pathogens. A key event in the evolution of the highly virulent plague bacterium Yersinia pestis was the acquisition of plasmid pPCP1, which carries the plasminogen activator gene, pla. This promoted the bubonic form of the disease by increasing bacterial dissemination from flea bite sites and incidentally enhanced replication in respiratory airways during pneumonic infection. We determined that expression of pla is controlled by the global regulator cyclic AMP (cAMP) receptor protein (Crp). This transcription factor is well conserved among distantly related bacteria, where it acts as a soluble receptor for the ubiquitous signaling molecule cAMP and controls a global network of metabolic and stress-protective genes. Crp has a similar physiological role in Y. pestis since loss of its function resulted in an inability to metabolize a variety of nonglucose substrates. Activation of pla expression requires a transcription activation element of the pla promoter that serves as a Crp binding site. Crp interaction with this site was demonstrated to occur only in the presence of cAMP. Alteration of the Crp binding site nucleotide sequence prevented in vitro formation of Crp-DNA complexes and inhibited in vivo expression of pla. The placement of pla under direct regulatory control of Crp highlights how highly adapted pathogens integrate laterally acquired genes to coordinate virulence factor expression with global gene networks to maintain homeostasis through the infectious life cycle.

Original languageEnglish (US)
Pages (from-to)8890-8900
Number of pages11
JournalJournal of Bacteriology
Volume189
Issue number24
DOIs
StatePublished - Dec 2007

Fingerprint

Cyclic AMP Receptor Protein
Yersinia pestis
Plasminogen Activators
Genes
Protein Binding
Cyclic AMP
Binding Sites
Bacteria
Siphonaptera
Horizontal Gene Transfer
Physiological Stress
Plague
Gene Regulatory Networks
Virulence Factors
Bites and Stings
Life Cycle Stages
Transcriptional Activation
Plasmids
Homeostasis
Transcription Factors

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Immunology

Cite this

Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein. / Kim, Tae Jong; Chauhan, Sadhana; Motin, Vladimir; Goh, Ee Been; Igo, Michèle M.; Young, Glenn M.

In: Journal of Bacteriology, Vol. 189, No. 24, 12.2007, p. 8890-8900.

Research output: Contribution to journalArticle

Kim, Tae Jong ; Chauhan, Sadhana ; Motin, Vladimir ; Goh, Ee Been ; Igo, Michèle M. ; Young, Glenn M. / Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein. In: Journal of Bacteriology. 2007 ; Vol. 189, No. 24. pp. 8890-8900.
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