PMID- 14726534
OWN - NLM
STAT- MEDLINE
DCOM- 20040601
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 15
DP  - 2004 Apr 9
TI  - Quorum sensing in Staphylococci is regulated via phosphorylation of three 
      conserved histidine residues.
PG  - 14665-72
AB  - Staphylococcus aureus cause infections by producing toxins, a process regulated 
      by cell-cell communication (quorum sensing) through the histidine-phosphorylation 
      of the target of RNAIII-activating protein (TRAP). We show here that TRAP is 
      highly conserved in staphylococci and contains three completely conserved 
      histidine residues (His-66, His-79, His-154) that are phosphorylated and 
      essential for its activity. This was tested by constructing a TRAP(-) strain with 
      each of the conserved histidine residues changed to alanine by site-directed 
      mutagenesis. All mutants were tested for pathogenesis in vitro (expression of 
      RNAIII and hemolytic activity) and in vivo (murine cellulitis model). Results 
      show that RNAIII is not expressed in the TRAP(-) strain, that it is non 
      hemolytic, and that it does not cause disease in vivo. These pathogenic 
      phenotypes could be rescued in the strain containing the recovered traP, 
      confirming the importance of TRAP in S. aureus pathogenesis. The phosphorylation 
      of TRAP mutated in any of the conserved histidine residues was significantly 
      reduced, and mutants defective in any one of these residues were non-pathogenic 
      in vitro or in vivo, whereas those mutated in a non-conserved histidine residue 
      (His-124) were as pathogenic as the wild type. These results confirm the 
      importance of the three conserved histidine residues in TRAP activity. The 
      phosphorylation pattern, structure, and gene organization of TRAP deviates from 
      signaling molecules known to date, suggesting that TRAP belongs to a novel class 
      of signal transducers.
FAU - Gov, Yael
AU  - Gov Y
AD  - Department of Human Microbiology, Sackler School of Medicine, George S. Wise 
      Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
FAU - Borovok, Ilya
AU  - Borovok I
FAU - Korem, Moshe
AU  - Korem M
FAU - Singh, Vineet K
AU  - Singh VK
FAU - Jayaswal, Radheshyam K
AU  - Jayaswal RK
FAU - Wilkinson, Brian J
AU  - Wilkinson BJ
FAU - Rich, Stephen M
AU  - Rich SM
FAU - Balaban, Naomi
AU  - Balaban N
LA  - eng
SI  - GENBANK/AJ489447
SI  - GENBANK/AJ489448
SI  - GENBANK/AJ489449
SI  - GENBANK/AJ489450
GR  - AI43970/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040114
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (RNA, Antisense)
RN  - 0 (RNA, Bacterial)
RN  - 0 (RNAIII, Staphylococcus aureus)
RN  - 4QD397987E (Histidine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Communication
MH  - DNA/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Escherichia coli/metabolism
MH  - Histidine/*chemistry
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Phenotype
MH  - Phosphorylation
MH  - Phylogeny
MH  - Plasmids/metabolism
MH  - Protein Structure, Tertiary
MH  - RNA, Antisense/chemistry
MH  - RNA, Bacterial/chemistry
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Staphylococcus aureus/*metabolism
MH  - Time Factors
EDAT- 2004/01/17 05:00
MHDA- 2004/06/02 05:00
CRDT- 2004/01/17 05:00
PHST- 2004/01/17 05:00 [pubmed]
PHST- 2004/06/02 05:00 [medline]
PHST- 2004/01/17 05:00 [entrez]
AID - S0021-9258(19)63857-3 [pii]
AID - 10.1074/jbc.M311106200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Apr 9;279(15):14665-72. doi: 10.1074/jbc.M311106200. Epub 2004 
      Jan 14.