Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi

Ming He, Jun Jie Zhang, Meiping Ye, Yongliang Lou, X. Yang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two twocomponent signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.

Original languageEnglish
Pages (from-to)445-452
Number of pages8
JournalInfection and Immunity
Volume82
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Borrelia burgdorferi
Virulence
Ticks
Gene Expression
Second Messenger Systems
Transcriptional Activation
Mammals
Signal Transduction
Genome
bis(3',5')-cyclic diguanylic acid
Infection
Proteins
cyclic GMP-binding protein

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi. / He, Ming; Zhang, Jun Jie; Ye, Meiping; Lou, Yongliang; Yang, X.

In: Infection and Immunity, Vol. 82, No. 1, 01.2014, p. 445-452.

Research output: Contribution to journalArticle

He, Ming ; Zhang, Jun Jie ; Ye, Meiping ; Lou, Yongliang ; Yang, X. / Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi. In: Infection and Immunity. 2014 ; Vol. 82, No. 1. pp. 445-452.
@article{b31dfe89795b4688bfbe565914af1c58,
title = "Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi",
abstract = "As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two twocomponent signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.",
author = "Ming He and Zhang, {Jun Jie} and Meiping Ye and Yongliang Lou and X. Yang",
year = "2014",
month = "1",
doi = "10.1128/IAI.01238-13",
language = "English",
volume = "82",
pages = "445--452",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi

AU - He, Ming

AU - Zhang, Jun Jie

AU - Ye, Meiping

AU - Lou, Yongliang

AU - Yang, X.

PY - 2014/1

Y1 - 2014/1

N2 - As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two twocomponent signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.

AB - As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two twocomponent signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.

UR - http://www.scopus.com/inward/record.url?scp=84890820130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890820130&partnerID=8YFLogxK

U2 - 10.1128/IAI.01238-13

DO - 10.1128/IAI.01238-13

M3 - Article

VL - 82

SP - 445

EP - 452

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 1

ER -