PMID- 36191190
OWN - NLM
STAT- MEDLINE
DCOM- 20221005
LR  - 20221027
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 119
IP  - 41
DP  - 2022 Oct 11
TI  - Elongation factor P modulates Acinetobacter baumannii physiology and virulence as 
      a cyclic dimeric guanosine monophosphate effector.
PG  - e2209838119
LID - 10.1073/pnas.2209838119 [doi]
LID - e2209838119
AB  - Cyclic diguanosine monophosphate (c-di-GMP) is widely used by bacteria to control 
      biological functions in response to diverse signals or cues. A previous study 
      showed that potential c-di-GMP metabolic enzymes play a role in the regulation of 
      biofilm formation and motility in Acinetobacter baumannii. However, it was 
      unclear whether and how A. baumannii cells use c-di-GMP signaling to modulate 
      biological functions. Here, we report that c-di-GMP is an important intracellular 
      signal in the modulation of biofilm formation, motility, and virulence in A. 
      baumannii. The intracellular level of c-di-GMP is principally controlled by the 
      diguanylate cyclases (DGCs) A1S_1695, A1S_2506, and A1S_3296 and the 
      phosphodiesterase (PDE) A1S_1254. Intriguingly, we revealed that A1S_2419 (an 
      elongation factor P [EF-P]), is a novel c-di-GMP effector in A. baumannii. 
      Response to a c-di-GMP signal boosted A1S_2419 activity to rescue ribosomes from 
      stalling during synthesis of proteins containing consecutive prolines and thus 
      regulate A. baumannii physiology and pathogenesis. Our study presents a unique 
      and widely conserved effector that controls bacterial physiology and virulence by 
      sensing the second messenger c-di-GMP.
FAU - Guo, Quan
AU  - Guo Q
AUID- ORCID: 0000-0002-0615-7311
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
FAU - Cui, Binbin
AU  - Cui B
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
FAU - Wang, Mingfang
AU  - Wang M
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
FAU - Li, Xia
AU  - Li X
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
FAU - Tan, Huihui
AU  - Tan H
AUID- ORCID: 0000-0001-8182-5706
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
FAU - Song, Shihao
AU  - Song S
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
FAU - Zhou, Jianuan
AU  - Zhou J
AD  - Integrative Microbiology Research Center, College of Plant Protection, South 
      China Agricultural University, Guangzhou 510642, China.
FAU - Zhang, Lian-Hui
AU  - Zhang LH
AD  - Integrative Microbiology Research Center, College of Plant Protection, South 
      China Agricultural University, Guangzhou 510642, China.
FAU - Deng, Yinyue
AU  - Deng Y
AUID- ORCID: 0000-0003-1511-0870
AD  - School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen 
      University, Sun Yat-sen University, Shenzhen 518107, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221003
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Bacterial Proteins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Peptide Elongation Factors)
RN  - 0 (factor EF-P)
RN  - 85-32-5 (Guanosine Monophosphate)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 4.6.- (Phosphorus-Oxygen Lyases)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - *Acinetobacter baumannii/metabolism
MH  - Bacterial Proteins/genetics/metabolism
MH  - Biofilms
MH  - Cyclic GMP/metabolism
MH  - *Escherichia coli Proteins/metabolism
MH  - Gene Expression Regulation, Bacterial
MH  - Guanosine Monophosphate
MH  - Peptide Elongation Factors
MH  - Phosphoric Diester Hydrolases/metabolism
MH  - Phosphorus-Oxygen Lyases/genetics/metabolism
MH  - Virulence
PMC - PMC9564936
OTO - NOTNLM
OT  - Acinetobacter baumannii
OT  - c-di-GMP
OT  - elongation factor P
OT  - pathogenicity
OT  - physiology
COIS- The authors declare no competing interest.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/06 06:00
PMCR- 2022/10/03
CRDT- 2022/10/03 15:22
PHST- 2022/10/03 15:22 [entrez]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/06 06:00 [medline]
PHST- 2022/10/03 00:00 [pmc-release]
AID - 202209838 [pii]
AID - 10.1073/pnas.2209838119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2022 Oct 11;119(41):e2209838119. doi: 
      10.1073/pnas.2209838119. Epub 2022 Oct 3.