Copper primes adaptation of uropathogenic Escherichia coli to superoxide stress by activating superoxide dismutases.
Animals
Copper
/ pharmacology
Escherichia coli Infections
/ chemically induced
Female
Gene Expression Regulation, Bacterial
Host-Pathogen Interactions
/ drug effects
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Superoxide Dismutase
/ genetics
Superoxides
/ toxicity
Urinary Tract Infections
/ chemically induced
Uropathogenic Escherichia coli
/ drug effects
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
19
03
2020
accepted:
04
08
2020
revised:
08
09
2020
pubmed:
28
8
2020
medline:
20
9
2020
entrez:
27
8
2020
Statut:
epublish
Résumé
Copper and superoxide are used by the phagocytes to kill bacteria. Copper is a host effector encountered by uropathogenic Escherichia coli (UPEC) during urinary tract infection in a non-human primate model, and in humans. UPEC is exposed to higher levels of copper in the gut prior to entering the urinary tract. Effects of pre-exposure to copper on bacterial killing by superoxide has not been reported. We hypothesized that copper-replete E. coli is more sensitive to killing by superoxide in vitro, and in activated macrophages. We utilized wild-type UPEC strain CFT073, and its isogenic mutants lacking copper efflux systems, superoxide dismutases (SODs), regulators of a superoxide dismutase, and complemented mutants to address this question. Surprisingly, our results reveal that copper protects UPEC against killing by superoxide in vitro. This copper-dependent protection was amplified in the mutants lacking copper efflux systems. Increased levels of copper and manganese were detected in UPEC exposed to sublethal concentration of copper. Copper activated the transcription of sodA in a SoxR- and SoxS-dependent manner resulting in enhanced levels of SodA activity. Importantly, pre-exposure to copper increased the survival of UPEC within RAW264.7 and bone marrow-derived murine macrophages. Loss of SodA, but not SodB or SodC, in UPEC obliterated copper-dependent protection from superoxide in vitro, and from killing within macrophages. Collectively, our results suggest a model in which sublethal levels of copper trigger the activation of SodA and SodC through independent mechanisms that converge to promote the survival of UPEC from killing by superoxide. A major implication of our findings is that bacteria colonizing copper-rich milieus are primed for efficient detoxification of superoxide.
Identifiants
pubmed: 32845936
doi: 10.1371/journal.ppat.1008856
pii: PPATHOGENS-D-20-00531
pmc: PMC7478841
doi:
Substances chimiques
Superoxides
11062-77-4
Copper
789U1901C5
Superoxide Dismutase
EC 1.15.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008856Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK114224
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135645
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Mutat Res. 1997 Mar 17;389(2-3):237-42
pubmed: 9093389
Biochem J. 1987 Feb 15;242(1):103-7
pubmed: 3036079
Mol Microbiol. 2013 Feb;87(3):466-77
pubmed: 23171030
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18327-32
pubmed: 25489107
Mol Microbiol. 2009 May;72(4):844-58
pubmed: 19400769
Microbiol Spectr. 2015 Aug;3(4):
pubmed: 26350328
mBio. 2013 Feb 12;4(1):e00023-13
pubmed: 23404396
Nat Protoc. 2010 Jan;5(1):51-66
pubmed: 20057381
J Bacteriol. 1991 Jul;173(14):4433-9
pubmed: 1648558
Metallomics. 2015 Jun;7(6):935-42
pubmed: 25677827
Nat Chem Biol. 2012 Aug;8(8):731-6
pubmed: 22772152
Nat Rev Microbiol. 2012 Nov;10(11):743-54
pubmed: 23042564
J Bacteriol. 2001 Aug;183(15):4562-70
pubmed: 11443091
Mol Microbiol. 2005 Apr;56(1):215-27
pubmed: 15773991
Nat Chem Biol. 2017 Sep;13(9):1016-1021
pubmed: 28759019
Infect Immun. 1990 May;58(5):1281-9
pubmed: 2182540
Nat Rev Microbiol. 2015 May;13(5):269-84
pubmed: 25853778
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7502-7
pubmed: 10377444
Infect Immun. 2015 Apr;83(4):1443-50
pubmed: 25624354
J Infect Dis. 2001 Mar 1;183 Suppl 1:S1-4
pubmed: 11171002
Cell. 1985 Jul;41(3):753-62
pubmed: 2988786
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):652-6
pubmed: 10639134
J Biol Chem. 2001 Aug 17;276(33):30670-7
pubmed: 11399769
Mol Microbiol. 2002 Jan;43(1):95-106
pubmed: 11849539
Front Cell Infect Microbiol. 2013 Dec 05;3:90
pubmed: 24367764
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8344-9
pubmed: 19416816
Nature. 2001 Jan 25;409(6819):529-33
pubmed: 11206551
Mol Microbiol. 1999 Apr;32(1):179-91
pubmed: 10216871
Microbiology (Reading). 2001 Jun;147(Pt 6):1657-1670
pubmed: 11390697
J Bacteriol. 2005 Feb;187(3):912-22
pubmed: 15659669
J Infect Dis. 1999 Oct;180(4):1220-9
pubmed: 10479151
PLoS Pathog. 2009 Feb;5(2):e1000305
pubmed: 19229321
J Bacteriol. 2001 Jun;183(11):3399-407
pubmed: 11344148
Cell Microbiol. 2015 May;17(5):730-46
pubmed: 25410299
J Bacteriol. 2003 Jul;185(13):3804-12
pubmed: 12813074
Nature. 2017 Jun 22;546(7659):528-532
pubmed: 28614296
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
pubmed: 10829079
J Bacteriol. 2005 Mar;187(5):1591-603
pubmed: 15716429
Infect Immun. 1995 May;63(5):1739-44
pubmed: 7729880
J Biol Chem. 2009 Dec 4;284(49):33949-56
pubmed: 19808669
J Immunol. 2005 Feb 1;174(3):1491-500
pubmed: 15661908
Mol Microbiol. 2011 Mar;79(5):1136-50
pubmed: 21226770
Infect Immun. 2017 Feb 23;85(3):
pubmed: 28031261
ACS Chem Biol. 2014 Feb 21;9(2):551-61
pubmed: 24283977
Science. 1999 Apr 30;284(5415):805-8
pubmed: 10221913
Biochem J. 2012 May 15;444(1):51-7
pubmed: 22369063
J Biol Chem. 2015 Jul 31;290(31):18954-61
pubmed: 26055706
Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16669-74
pubmed: 17925449
Cell Host Microbe. 2016 Jun 8;19(6):814-25
pubmed: 27281571
J Bacteriol. 2008 Oct;190(20):6909-12
pubmed: 18723628
Nat Rev Urol. 2010 Dec;7(12):653-60
pubmed: 21139641
J Bacteriol. 1996 May;178(9):2564-71
pubmed: 8626323
Proc Natl Acad Sci U S A. 1990 Aug;87(16):6181-5
pubmed: 1696718
Biosci Biotechnol Biochem. 1999;63(3):485-8
pubmed: 27393255
EcoSal Plus. 2009 Aug;3(2):
pubmed: 26443771
J Urol. 1997 Mar;157(3):1127-9
pubmed: 9072556
J Bacteriol. 1990 Aug;172(8):4197-205
pubmed: 1695893
J Bacteriol. 2002 Jun;184(12):3151-8
pubmed: 12029030
J Bacteriol. 2001 Mar;183(6):2145-7
pubmed: 11222619
J Biol Chem. 2012 Apr 20;287(17):13549-55
pubmed: 22389498
PLoS Pathog. 2013;9(12):e1003788
pubmed: 24339777
Microbiology (Reading). 2005 Apr;151(Pt 4):1187-98
pubmed: 15817786
Nat Rev Microbiol. 2013 Jul;11(7):443-54
pubmed: 23712352
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13997-4001
pubmed: 9391141
J Bacteriol. 2007 Mar;189(5):1616-26
pubmed: 17189367
Infect Immun. 2017 Aug 18;85(9):
pubmed: 28652309
Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):6818-6823
pubmed: 28611214
Mol Microbiol. 2013 Dec;90(5):983-96
pubmed: 24112649