Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation.
bacterial metabolism
biofilm
cystic fibrosis
extracellular polysaccharide
immunometabolism
inflammation
itaconate
lipopolysaccharide
pneumonia
pseudomonas aeruginosa
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
received:
27
01
2020
revised:
31
03
2020
accepted:
21
04
2020
pubmed:
20
5
2020
medline:
10
11
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
The bacterium Pseudomonas aeruginosa is especially pathogenic, often being associated with intractable pneumonia and high mortality. How P. aeruginosa avoids immune clearance and persists in the inflamed human airway remains poorly understood. In this study, we show that P. aeruginosa can exploit the host immune response to maintain infection. Notably, unlike other opportunistic bacteria, we found that P. aeruginosa alters its metabolic and immunostimulatory properties in response to itaconate, an abundant host-derived immunometabolite in the infected lung. Itaconate induces bacterial membrane stress, resulting in downregulation of lipopolysaccharides (LPS) and upregulation of extracellular polysaccharides (EPS). These itaconate-adapted P. aeruginosa accumulate lptD mutations, which favor itaconate assimilation and biofilm formation. EPS, in turn, induces itaconate production by myeloid cells, both in the airway and systemically, skewing the host immune response to one permissive of chronic infection. Thus, the metabolic versatility of P. aeruginosa needs to be taken into account when designing therapies.
Identifiants
pubmed: 32428444
pii: S1550-4131(20)30199-6
doi: 10.1016/j.cmet.2020.04.017
pmc: PMC7272298
mid: NIHMS1589142
pii:
doi:
Substances chimiques
Succinates
0
itaconic acid
Q4516562YH
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1091-1106.e6Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL135800
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
J Infect Dis. 2005 Aug 1;192(3):410-9
pubmed: 15995954
Am J Respir Crit Care Med. 2014 Apr 1;189(7):799-811
pubmed: 24555512
J Bacteriol. 2001 Sep;183(18):5395-401
pubmed: 11514525
Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):15907-15913
pubmed: 31320588
Nature. 2018 Apr 5;556(7699):113-117
pubmed: 29590092
Cell Metab. 2016 Jul 12;24(1):158-66
pubmed: 27374498
Cell. 2016 Oct 6;167(2):457-470.e13
pubmed: 27667687
Appl Environ Microbiol. 2015 May 15;81(10):3349-56
pubmed: 25746989
J Antimicrob Chemother. 2008 May;61(5):1053-6
pubmed: 18256114
Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5125-E5134
pubmed: 29760087
Am J Respir Cell Mol Biol. 2018 Apr;58(4):428-439
pubmed: 29372812
Lancet. 2016 Nov 19;388(10059):2519-2531
pubmed: 27140670
Nature. 2013 Apr 11;496(7444):238-42
pubmed: 23535595
Front Microbiol. 2011 Aug 22;2:167
pubmed: 21991261
J Med Microbiol. 2018 Jan;67(1):1-21
pubmed: 29185941
Microbiology (Reading). 2008 Dec;154(Pt 12):3905-3916
pubmed: 19047757
Nat Rev Microbiol. 2008 Aug;6(8):613-24
pubmed: 18628769
Nat Chem Biol. 2019 Oct;15(10):983-991
pubmed: 31332308
Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12245-50
pubmed: 20566849
Res Microbiol. 1996 Jul-Sep;147(6-7):551-61
pubmed: 9084769
Nat Immunol. 2017 Apr 18;18(5):488-498
pubmed: 28418387
Antimicrob Agents Chemother. 2017 Jul 25;61(8):
pubmed: 28507116
Annu Rev Immunol. 2019 Apr 26;37:439-456
pubmed: 31026415
Cell Metab. 2019 Jan 8;29(1):211-220.e5
pubmed: 30293776
Infect Immun. 1995 Oct;63(10):4166-9
pubmed: 7558335
FEMS Microbiol Rev. 2010 Sep;34(5):658-84
pubmed: 20412307
Immunity. 2018 Jan 16;48(1):35-44.e6
pubmed: 29195811
PLoS Genet. 2014 Jul 24;10(7):e1004518
pubmed: 25057820
Antimicrob Agents Chemother. 2015 Nov 23;60(2):845-54
pubmed: 26596941
Infect Control Hosp Epidemiol. 2019 May;40(5):597-599
pubmed: 30975229
J Bacteriol. 2000 Jan;182(2):425-31
pubmed: 10629189
Trends Microbiol. 1995 Sep;3(9):351-6
pubmed: 8520888
Trends Microbiol. 2016 May;24(5):327-337
pubmed: 26946977
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8717-22
pubmed: 27439868
J Bacteriol. 1998 Apr;180(7):1741-9
pubmed: 9537370
Nat Chem Biol. 2014 May;10(5):371-7
pubmed: 24657929
PLoS Pathog. 2016 Feb 01;12(2):e1005408
pubmed: 26829557
Science. 2013 May 17;340(6134):837-41
pubmed: 23687042
Nature. 2018 Apr;556(7702):501-504
pubmed: 29670287
Mol Microbiol. 1994 Aug;13(3):427-34
pubmed: 7527892
Future Microbiol. 2017 Apr;12:379-392
pubmed: 28339291
Arch Biochem Biophys. 1974 Jul;163(1):79-86
pubmed: 4852477
PLoS One. 2018 Oct 16;13(10):e0205815
pubmed: 30325949
BMJ. 2017 Jul 10;358:j2471
pubmed: 28694251
J Infect. 2017 Feb;74(2):142-152
pubmed: 27865895
J Biotechnol. 2014 Dec 10;191:121-30
pubmed: 25240440
Front Microbiol. 2011 May 05;2:103
pubmed: 21833336
Blood. 2010 Jan 21;115(3):e10-9
pubmed: 19965649
Immunity. 2017 Dec 19;47(6):1169-1181.e7
pubmed: 29246444
Nat Commun. 2019 Apr 30;10(1):1999
pubmed: 31040289
Autophagy. 2015;11(1):166-82
pubmed: 25700738
Sci Transl Med. 2019 Jul 3;11(499):
pubmed: 31270271
Structure. 2016 Jun 7;24(6):965-976
pubmed: 27161977