PMID- 28066723
OWN - NLM
STAT- MEDLINE
DCOM- 20170922
LR  - 20240326
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 6
DP  - 2016
TI  - Coxiella burnetii Employs the Dot/Icm Type IV Secretion System to Modulate Host 
      NF-kappaB/RelA Activation.
PG  - 188
LID - 10.3389/fcimb.2016.00188 [doi]
LID - 188
AB  - Coxiella burnetii is the causative agent of Q fever and an obligate intracellular 
      pathogen in nature that survives and grows in a parasitophorous vacuole (PV) 
      within eukaryotic host cells. C. burnetii promotes intracellular survival by 
      subverting apoptotic and pro-inflammatory signaling pathways that are typically 
      regulated by nuclear transcription factor-kappaB (NF-kappaB). We and others have 
      demonstrated that C. burnetii NMII proteins inhibit expression of 
      pro-inflammatory cytokines and induce expression of anti-apoptotic genes during 
      infection. Here, we demonstrate that C. burnetii promotes intracellular survival 
      by modulating NF-kappaB subunit p65 (RelA) phosphorylation, and thus activation, in a 
      Type Four B Secretion System (T4BSS)-dependent manner. Immunoblot analysis of 
      RelA phosphorylated at serine-536 demonstrated that C. burnetii increases NF-kappaB 
      activation via the canonical pathway. However, RelA phosphorylation levels were 
      even higher in infected cells where bacterial protein or mRNA synthesis was 
      inhibited. Importantly, we demonstrate that inhibition of RelA phosphorylation 
      impairs PV formation and C. burnetii growth. We found that a T4BSS-defective 
      mutant (CbDeltadotA) elicited phosphorylated RelA levels similar to those of wild 
      type C. burnetii infection treated with Chloramphenicol. Moreover, cells infected 
      with CbDeltadotA or wild type C. burnetii treated with Chloramphenicol showed similar 
      levels of GFP-RelA nuclear localization, and significantly increased localization 
      compared to wild type C. burnetii infection. These data indicate that without de 
      novo protein synthesis and a functional T4BSS, C. burnetii is unable to modulate 
      NF-kappaB activation, which is crucial for optimal intracellular growth.
FAU - Mahapatra, Saugata
AU  - Mahapatra S
AD  - Department of Microbiology and Molecular genetics, Oklahoma State University 
      Stillwater, OK, USA.
FAU - Gallaher, Brandi
AU  - Gallaher B
AD  - Department of Microbiology and Molecular genetics, Oklahoma State University 
      Stillwater, OK, USA.
FAU - Smith, Sydni Caet
AU  - Smith SC
AD  - Department of Microbiology and Molecular genetics, Oklahoma State University 
      Stillwater, OK, USA.
FAU - Graham, Joseph G
AU  - Graham JG
AD  - Department of Microbiology and Immunology, University of Arkansas for Medical 
      Sciences (UAMS) Little Rock, AR, USA.
FAU - Voth, Daniel E
AU  - Voth DE
AD  - Department of Microbiology and Immunology, University of Arkansas for Medical 
      Sciences (UAMS) Little Rock, AR, USA.
FAU - Shaw, Edward I
AU  - Shaw EI
AD  - Department of Microbiology and Molecular genetics, Oklahoma State University 
      Stillwater, OK, USA.
LA  - eng
GR  - R01 AI087669/AI/NIAID NIH HHS/United States
GR  - R15 AI072710/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161219
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Bacterial Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p52 Subunit)
RN  - 0 (RELA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Type IV Secretion Systems)
RN  - 66974FR9Q1 (Chloramphenicol)
SB  - IM
MH  - Bacterial Proteins/metabolism
MH  - Cell Line/microbiology
MH  - Chloramphenicol/pharmacology
MH  - Coxiella burnetii/drug effects/genetics/growth & development/*metabolism
MH  - Epithelial Cells/microbiology
MH  - HeLa Cells
MH  - Host-Parasite Interactions
MH  - Humans
MH  - Mutation
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p52 Subunit/metabolism
MH  - Phosphorylation
MH  - Q Fever/immunology/*microbiology
MH  - RNA, Messenger/biosynthesis
MH  - Signal Transduction
MH  - Transcription Factor RelA/*metabolism
MH  - Type IV Secretion Systems/genetics/*metabolism
MH  - Vacuoles/microbiology
MH  - Wnt Signaling Pathway
PMC - PMC5165255
OTO - NOTNLM
OT  - Coxiella burnetii
OT  - NF-kappaB
OT  - Q fever
OT  - obligate intracellular
OT  - type four secretion system
EDAT- 2017/01/10 06:00
MHDA- 2017/09/25 06:00
PMCR- 2016/01/01
CRDT- 2017/01/10 06:00
PHST- 2016/10/16 00:00 [received]
PHST- 2016/12/02 00:00 [accepted]
PHST- 2017/01/10 06:00 [entrez]
PHST- 2017/01/10 06:00 [pubmed]
PHST- 2017/09/25 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2016.00188 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2016 Dec 19;6:188. doi: 10.3389/fcimb.2016.00188. 
      eCollection 2016.