Chromosomally-Encoded Yersinia pestis Type III Secretion Effector Proteins Promote Infection in Cells and in Mice

Sara Schesser Bartra, Cherish Lorica, Lianfen Qian, Xin Gong, Wael Bahnan, Henry Barreras, Rosmely Hernandez, Zhongwei Li, Gregory V Plano, Kurt Schesser

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Yersinia pestis, the causative agent of plague, possesses a number of virulence mechanisms that allows it to survive and proliferate during its interaction with the host. To discover additional infection-specific Y. pestis factors, a transposon site hybridization (TraSH)-based genome-wide screen was employed to identify genomic regions required for its survival during cellular infection. In addition to several well-characterized infection-specific genes, this screen identified three chromosomal genes (y3397, y3399, and y3400), located in an apparent operon, that promoted successful infection. Each of these genes is predicted to encode a leucine-rich repeat family protein with or without an associated ubiquitin E3 ligase domain. These genes were designated Yersinia leucine-rich repeat gene A (ylrA), B (ylrB), and C (ylrC). Engineered strains with deletions of y3397 (ylrC), y3399 (ylrB), or y3400 (ylrA), exhibited infection defects both in cultured cells and in the mouse. C-terminal FLAG-tagged YlrA, YlrB, and YlrC were secreted by Y. pestis in the absence but not the presence of extracellular calcium and deletions of the DNA sequences encoding the predicted N-terminal type III secretion signals of YlrA, YlrB, and YlrC prevented their secretion, indicating that these proteins are substrates of the type III secretion system (T3SS). Further strengthening the connection with the T3SS, YlrB was readily translocated into HeLa cells and expression of the YlrA and YlrC proteins in yeast inhibited yeast growth, indicating that these proteins may function as anti-host T3S effector proteins.

Original languageEnglish (US)
Number of pages1
JournalFrontiers in Cellular and Infection Microbiology
Volume9
DOIs
StatePublished - Jan 1 2019

Fingerprint

Yersinia pestis
Infection
Genes
Yersinia
Proteins
Leucine
Ubiquitin-Protein Ligases
Fungal Proteins
Plague
Operon
HeLa Cells
Virulence
Cultured Cells
Yeasts
Genome
Calcium
Growth

Keywords

  • leucine rich repeats
  • mice
  • pathogenesis
  • plague
  • type III secretion
  • Yersinia

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Chromosomally-Encoded Yersinia pestis Type III Secretion Effector Proteins Promote Infection in Cells and in Mice. / Schesser Bartra, Sara; Lorica, Cherish; Qian, Lianfen; Gong, Xin; Bahnan, Wael; Barreras, Henry; Hernandez, Rosmely; Li, Zhongwei; Plano, Gregory V; Schesser, Kurt.

In: Frontiers in Cellular and Infection Microbiology, Vol. 9, 01.01.2019.

Research output: Contribution to journalArticle

Schesser Bartra, Sara ; Lorica, Cherish ; Qian, Lianfen ; Gong, Xin ; Bahnan, Wael ; Barreras, Henry ; Hernandez, Rosmely ; Li, Zhongwei ; Plano, Gregory V ; Schesser, Kurt. / Chromosomally-Encoded Yersinia pestis Type III Secretion Effector Proteins Promote Infection in Cells and in Mice. In: Frontiers in Cellular and Infection Microbiology. 2019 ; Vol. 9.
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AU - Schesser Bartra, Sara

AU - Lorica, Cherish

AU - Qian, Lianfen

AU - Gong, Xin

AU - Bahnan, Wael

AU - Barreras, Henry

AU - Hernandez, Rosmely

AU - Li, Zhongwei

AU - Plano, Gregory V

AU - Schesser, Kurt

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N2 - Yersinia pestis, the causative agent of plague, possesses a number of virulence mechanisms that allows it to survive and proliferate during its interaction with the host. To discover additional infection-specific Y. pestis factors, a transposon site hybridization (TraSH)-based genome-wide screen was employed to identify genomic regions required for its survival during cellular infection. In addition to several well-characterized infection-specific genes, this screen identified three chromosomal genes (y3397, y3399, and y3400), located in an apparent operon, that promoted successful infection. Each of these genes is predicted to encode a leucine-rich repeat family protein with or without an associated ubiquitin E3 ligase domain. These genes were designated Yersinia leucine-rich repeat gene A (ylrA), B (ylrB), and C (ylrC). Engineered strains with deletions of y3397 (ylrC), y3399 (ylrB), or y3400 (ylrA), exhibited infection defects both in cultured cells and in the mouse. C-terminal FLAG-tagged YlrA, YlrB, and YlrC were secreted by Y. pestis in the absence but not the presence of extracellular calcium and deletions of the DNA sequences encoding the predicted N-terminal type III secretion signals of YlrA, YlrB, and YlrC prevented their secretion, indicating that these proteins are substrates of the type III secretion system (T3SS). Further strengthening the connection with the T3SS, YlrB was readily translocated into HeLa cells and expression of the YlrA and YlrC proteins in yeast inhibited yeast growth, indicating that these proteins may function as anti-host T3S effector proteins.

AB - Yersinia pestis, the causative agent of plague, possesses a number of virulence mechanisms that allows it to survive and proliferate during its interaction with the host. To discover additional infection-specific Y. pestis factors, a transposon site hybridization (TraSH)-based genome-wide screen was employed to identify genomic regions required for its survival during cellular infection. In addition to several well-characterized infection-specific genes, this screen identified three chromosomal genes (y3397, y3399, and y3400), located in an apparent operon, that promoted successful infection. Each of these genes is predicted to encode a leucine-rich repeat family protein with or without an associated ubiquitin E3 ligase domain. These genes were designated Yersinia leucine-rich repeat gene A (ylrA), B (ylrB), and C (ylrC). Engineered strains with deletions of y3397 (ylrC), y3399 (ylrB), or y3400 (ylrA), exhibited infection defects both in cultured cells and in the mouse. C-terminal FLAG-tagged YlrA, YlrB, and YlrC were secreted by Y. pestis in the absence but not the presence of extracellular calcium and deletions of the DNA sequences encoding the predicted N-terminal type III secretion signals of YlrA, YlrB, and YlrC prevented their secretion, indicating that these proteins are substrates of the type III secretion system (T3SS). Further strengthening the connection with the T3SS, YlrB was readily translocated into HeLa cells and expression of the YlrA and YlrC proteins in yeast inhibited yeast growth, indicating that these proteins may function as anti-host T3S effector proteins.

KW - leucine rich repeats

KW - mice

KW - pathogenesis

KW - plague

KW - type III secretion

KW - Yersinia

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