RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinantCitation formats

  • External authors:
  • Heba Barnawi
  • Nader Masri
  • Natasha Hussain
  • Bushra Al-lawati
  • Evita Mayasari
  • Aleksandra Gulbicka
  • Min-hsuan Huang

Standard

RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant. / Barnawi, Heba; Masri, Nader; Hussain, Natasha; Al-lawati, Bushra; Mayasari, Evita; Gulbicka, Aleksandra; Jervis, Adrian J.; Huang, Min-hsuan; Cavet, Jennifer S.; Linton, Dennis.

In: PLoS Pathogens, Vol. 16, No. 10, e1009008, 16.10.2020, p. 0.

Research output: Contribution to journalArticlepeer-review

Harvard

Barnawi, H, Masri, N, Hussain, N, Al-lawati, B, Mayasari, E, Gulbicka, A, Jervis, AJ, Huang, M, Cavet, JS & Linton, D 2020, 'RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant', PLoS Pathogens, vol. 16, no. 10, e1009008, pp. 0. https://doi.org/10.1371/journal.ppat.1009008

APA

Barnawi, H., Masri, N., Hussain, N., Al-lawati, B., Mayasari, E., Gulbicka, A., Jervis, A. J., Huang, M., Cavet, J. S., & Linton, D. (2020). RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant. PLoS Pathogens, 16(10), 0. [e1009008]. https://doi.org/10.1371/journal.ppat.1009008

Vancouver

Barnawi H, Masri N, Hussain N, Al-lawati B, Mayasari E, Gulbicka A et al. RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant. PLoS Pathogens. 2020 Oct 16;16(10):0. e1009008. https://doi.org/10.1371/journal.ppat.1009008

Author

Barnawi, Heba ; Masri, Nader ; Hussain, Natasha ; Al-lawati, Bushra ; Mayasari, Evita ; Gulbicka, Aleksandra ; Jervis, Adrian J. ; Huang, Min-hsuan ; Cavet, Jennifer S. ; Linton, Dennis. / RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant. In: PLoS Pathogens. 2020 ; Vol. 16, No. 10. pp. 0.

Bibtex

@article{f81f87ee97344826a9f1dee351cfa29f,
title = "RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant",
abstract = "RNA thermometers (RNATs) trigger bacterial virulence factor expression in response to the temperature shift on entering a warm-blooded host. At lower temperatures these secondary structures sequester ribosome-binding sites (RBSs) to prevent translation initiation, whereas at elevated temperatures they “melt” allowing translation. Campylobacter jejuni is the leading bacterial cause of human gastroenteritis worldwide yet little is known about how it interacts with the host including host induced gene regulation. Here we demonstrate that an RNAT regulates a C. jejuni gene, Cj1163c or czcD, encoding a member of the Cation Diffusion Facilitator family. The czcD upstream untranslated region contains a predicted stem loop within the mRNA that sequesters the RBS to inhibit translation at temperatures below 37°C. Mutations that disrupt or enhance predicted secondary structure have significant and predictable effects on temperature regulation. We also show that in an RNAT independent manner, CzcD expression is induced by Zn(II). Mutants lacking czcD are hypersensitive to Zn(II) and also over-accumulate Zn(II) relative to wild-type, all consistent with CzcD functioning as a Zn(II) exporter. Importantly, we demonstrate that C. jejuni Zn(II)-tolerance at 32°C, a temperature at which the RNAT limits CzcD production, is increased by RNAT disruption. Finally we show that czcD inactivation attenuates larval killing in a Galleria infection model and that at 32°C disrupting RNAT secondary structure to allow CzcD production can enhance killing. We hypothesise that CzcD regulation by metals and temperature provides a mechanism for C. jejuni to overcome innate immune system-mediated Zn(II) toxicity in warm-blooded animal hosts.",
keywords = "Bacteria/genetics, Body Temperature Regulation/genetics, Campylobacter Infections/genetics, Campylobacter jejuni/genetics, Gene Expression Regulation, Bacterial/genetics, Nucleic Acid Conformation, RNA, Bacterial/genetics, RNA, Messenger/genetics, RNA/genetics, Temperature, Virulence, Virulence Factors/metabolism, Zinc/metabolism",
author = "Heba Barnawi and Nader Masri and Natasha Hussain and Bushra Al-lawati and Evita Mayasari and Aleksandra Gulbicka and Jervis, {Adrian J.} and Min-hsuan Huang and Cavet, {Jennifer S.} and Dennis Linton",
note = "Funding Information: HB was supported by a scholarship from the University of Hail, Saudi Arabia, EM by the Indonesia Endowment Fund for Education, NH by a Commonwealth scholarship and BA by a scholarship from Ministry of Higher Education, Sultanate of Oman. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright {\textcopyright} 2020 Barnawi et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = oct,
day = "16",
doi = "10.1371/journal.ppat.1009008",
language = "English",
volume = "16",
pages = "0",
journal = "PL o S Pathogens",
issn = "1553-7374",
publisher = "Public Library of Science",
number = "10",

}

RIS

TY - JOUR

T1 - RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant

AU - Barnawi, Heba

AU - Masri, Nader

AU - Hussain, Natasha

AU - Al-lawati, Bushra

AU - Mayasari, Evita

AU - Gulbicka, Aleksandra

AU - Jervis, Adrian J.

AU - Huang, Min-hsuan

AU - Cavet, Jennifer S.

AU - Linton, Dennis

N1 - Funding Information: HB was supported by a scholarship from the University of Hail, Saudi Arabia, EM by the Indonesia Endowment Fund for Education, NH by a Commonwealth scholarship and BA by a scholarship from Ministry of Higher Education, Sultanate of Oman. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright © 2020 Barnawi et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10/16

Y1 - 2020/10/16

N2 - RNA thermometers (RNATs) trigger bacterial virulence factor expression in response to the temperature shift on entering a warm-blooded host. At lower temperatures these secondary structures sequester ribosome-binding sites (RBSs) to prevent translation initiation, whereas at elevated temperatures they “melt” allowing translation. Campylobacter jejuni is the leading bacterial cause of human gastroenteritis worldwide yet little is known about how it interacts with the host including host induced gene regulation. Here we demonstrate that an RNAT regulates a C. jejuni gene, Cj1163c or czcD, encoding a member of the Cation Diffusion Facilitator family. The czcD upstream untranslated region contains a predicted stem loop within the mRNA that sequesters the RBS to inhibit translation at temperatures below 37°C. Mutations that disrupt or enhance predicted secondary structure have significant and predictable effects on temperature regulation. We also show that in an RNAT independent manner, CzcD expression is induced by Zn(II). Mutants lacking czcD are hypersensitive to Zn(II) and also over-accumulate Zn(II) relative to wild-type, all consistent with CzcD functioning as a Zn(II) exporter. Importantly, we demonstrate that C. jejuni Zn(II)-tolerance at 32°C, a temperature at which the RNAT limits CzcD production, is increased by RNAT disruption. Finally we show that czcD inactivation attenuates larval killing in a Galleria infection model and that at 32°C disrupting RNAT secondary structure to allow CzcD production can enhance killing. We hypothesise that CzcD regulation by metals and temperature provides a mechanism for C. jejuni to overcome innate immune system-mediated Zn(II) toxicity in warm-blooded animal hosts.

AB - RNA thermometers (RNATs) trigger bacterial virulence factor expression in response to the temperature shift on entering a warm-blooded host. At lower temperatures these secondary structures sequester ribosome-binding sites (RBSs) to prevent translation initiation, whereas at elevated temperatures they “melt” allowing translation. Campylobacter jejuni is the leading bacterial cause of human gastroenteritis worldwide yet little is known about how it interacts with the host including host induced gene regulation. Here we demonstrate that an RNAT regulates a C. jejuni gene, Cj1163c or czcD, encoding a member of the Cation Diffusion Facilitator family. The czcD upstream untranslated region contains a predicted stem loop within the mRNA that sequesters the RBS to inhibit translation at temperatures below 37°C. Mutations that disrupt or enhance predicted secondary structure have significant and predictable effects on temperature regulation. We also show that in an RNAT independent manner, CzcD expression is induced by Zn(II). Mutants lacking czcD are hypersensitive to Zn(II) and also over-accumulate Zn(II) relative to wild-type, all consistent with CzcD functioning as a Zn(II) exporter. Importantly, we demonstrate that C. jejuni Zn(II)-tolerance at 32°C, a temperature at which the RNAT limits CzcD production, is increased by RNAT disruption. Finally we show that czcD inactivation attenuates larval killing in a Galleria infection model and that at 32°C disrupting RNAT secondary structure to allow CzcD production can enhance killing. We hypothesise that CzcD regulation by metals and temperature provides a mechanism for C. jejuni to overcome innate immune system-mediated Zn(II) toxicity in warm-blooded animal hosts.

KW - Bacteria/genetics

KW - Body Temperature Regulation/genetics

KW - Campylobacter Infections/genetics

KW - Campylobacter jejuni/genetics

KW - Gene Expression Regulation, Bacterial/genetics

KW - Nucleic Acid Conformation

KW - RNA, Bacterial/genetics

KW - RNA, Messenger/genetics

KW - RNA/genetics

KW - Temperature

KW - Virulence

KW - Virulence Factors/metabolism

KW - Zinc/metabolism

U2 - 10.1371/journal.ppat.1009008

DO - 10.1371/journal.ppat.1009008

M3 - Article

C2 - 33064782

VL - 16

SP - 0

JO - PL o S Pathogens

JF - PL o S Pathogens

SN - 1553-7374

IS - 10

M1 - e1009008

ER -