Plasma membrane damage repair is mediated by an acid sphingomyelinase in Entamoeba histolytica.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
27
04
2019
accepted:
02
08
2019
entrez:
29
8
2019
pubmed:
29
8
2019
medline:
16
1
2020
Statut:
epublish
Résumé
Entamoeba histolytica is a pathogen that during its infective process confronts the host defenses, which damages the amoebic plasma membrane (PM), resulting in the loss of viability. However, it is unknown whether amoebic trophozoites are able to repair their PM when it is damaged. Acid sphingomyelinases (aSMases) have been reported in mammalian cells to promote endocytosis and removal of PM lesions. In this work, six predicted amoebic genes encoding for aSMases were found to be transcribed in the HM1:IMSS strain, finding that the EhaSM6 gene is the most transcribed in basal growth conditions and rendered a functional protein. The secreted aSMase activity detected was stimulated by Mg+2 and inhibited by Co+2. Trophozoites that overexpress the EhaSM6 gene (HM1-SM6HA) exhibit an increase of 2-fold in the secreted aSMase activity. This transfectant trophozoites exposed to pore-forming molecules (SLO, Magainin, β-Defensin 2 and human complement) exhibited an increase from 6 to 25-fold in the secreted aSMase activity which correlated with higher amoebic viability in a Ca+2 dependent process. However, other agents that affect the PM such as hydrogen peroxide also induced an increase of secreted aSMase, but to a lesser extent. The aSMase6 enzyme is N- and C-terminal processed. Confocal and transmission electron microscopy showed that trophozoites treated with SLO presented a migration of lysosomes containing the aSMase towards the PM, inducing the formation of membrane patches and endosomes in the control strain. These cellular structures were increased in the overexpressing strain, indicating the involvement of the aSMase6 in the PM injury repair. The pore-forming molecules induced an increase in the expression of EhaSM1, 2, 5 and 6 genes, meanwhile, hydrogen peroxide induced an increase in all of them. In all the conditions evaluated, the EhaSM6 gene exhibited the highest levels of induction. Overall, these novel findings show that the aSMase6 enzyme from E. histolytica promotes the repair of the PM damaged with pore-forming molecules to prevent losing cell integrity. This novel system could act when encountered with the lytic defense systems of the host.
Identifiants
pubmed: 31461501
doi: 10.1371/journal.ppat.1008016
pii: PPATHOGENS-D-19-00791
pmc: PMC6713333
doi:
Substances chimiques
acid sphingomyelinase-1
EC 3.1.4.-
Sphingomyelin Phosphodiesterase
EC 3.1.4.12
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008016Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Cell. 1997 Nov 28;91(5):605-15
pubmed: 9393854
Physiol Rev. 2000 Oct;80(4):1483-521
pubmed: 11015619
Future Microbiol. 2011 Mar;6(3):255-8
pubmed: 21449836
J Lipid Res. 1976 Sep;17(5):506-15
pubmed: 9463
Cell Microbiol. 2012 Aug;14(8):1299-317
pubmed: 22486861
Nat Immunol. 2002 Nov;3(11):1041-7
pubmed: 12407413
J Biol Chem. 2011 Feb 4;286(5):3777-88
pubmed: 21098024
J Biol Chem. 2004 Nov 19;279(47):49497-507
pubmed: 15347665
Semin Cell Dev Biol. 2015 Sep;45:10-7
pubmed: 26433178
J Cell Physiol. 2000 Sep;184(3):285-300
pubmed: 10911359
Infect Immun. 1985 Jan;47(1):52-60
pubmed: 3880730
FEBS Lett. 1996 Dec 16;399(3):227-31
pubmed: 8985151
Protein Sci. 2004 Dec;13(12):3172-86
pubmed: 15557261
Int Rev Cytol. 2002;216:59-80
pubmed: 12049210
Trends Cell Biol. 2008 Nov;18(11):552-9
pubmed: 18848451
Front Microbiol. 2015 Dec 15;6:1394
pubmed: 26696997
Immunol Res. 2011 Oct;51(1):45-60
pubmed: 21850539
Infect Immun. 1989 Jun;57(6):1750-6
pubmed: 2542164
Biochem J. 1994 Aug 1;301 ( Pt 3):855-62
pubmed: 8053910
Exp Parasitol. 2018 Nov;194:38-44
pubmed: 30253133
Biochimie. 2014 Dec;107 Pt A:66-72
pubmed: 25183513
Parasitol Today. 1997 May;13(5):190-4
pubmed: 15275090
J Exp Med. 1980 Aug 1;152(2):377-90
pubmed: 6249882
Microbiol Mol Biol Rev. 2013 Jun;77(2):173-207
pubmed: 23699254
J Virol. 2012 Jul;86(14):7473-83
pubmed: 22573858
Infect Immun. 2004 Feb;72(2):678-83
pubmed: 14742508
Mol Microbiol. 1994 Dec;14(5):895-904
pubmed: 7715451
Biochem Pharmacol. 2011 Mar 15;81(6):703-12
pubmed: 21219882
Lancet. 2003 Mar 22;361(9362):1025-34
pubmed: 12660071
Biol Reprod. 1999 Mar;60(3):683-90
pubmed: 10026116
J Vis Exp. 2013 Aug 25;(78):e50531
pubmed: 23995606
Immunology. 1986 Jul;58(3):467-71
pubmed: 2874111
Clin Microbiol Rev. 2000 Apr;13(2):196-206
pubmed: 10755997
J Biol Chem. 2004 May 7;279(19):20471-9
pubmed: 14993220
J Cell Sci. 2000 Jun;113 ( Pt 11):1891-902
pubmed: 10806100
Cell Signal. 2009 Jun;21(6):836-46
pubmed: 19385042
PLoS Negl Trop Dis. 2013;7(2):e2083
pubmed: 23469306
Oncogene. 2003 Oct 13;22(45):7070-7
pubmed: 14557812
J Biol Chem. 2010 Nov 12;285(46):35706-18
pubmed: 20807762
PLoS Pathog. 2016 Sep 09;12(9):e1005873
pubmed: 27611567
Sci Rep. 2017 Oct 9;7(1):12854
pubmed: 28993644
Protein Eng. 1997 Jan;10(1):1-6
pubmed: 9051728
Eukaryot Cell. 2004 Oct;3(5):1147-53
pubmed: 15470242
J Investig Med. 1996 Feb;44(2):24-36
pubmed: 8689398
J Biol Chem. 1998 Jul 17;273(29):18250-9
pubmed: 9660788
J Biol Chem. 2000 Jun 2;275(22):16484-9
pubmed: 10828058
J Exp Med. 2011 May 9;208(5):909-21
pubmed: 21536739
J Biol Chem. 1998 Jun 5;273(23):14374-9
pubmed: 9603947
Microbes Infect. 2009 Mar;11(3):384-93
pubmed: 19397883
Mucosal Immunol. 2008 Jan;1(1):11-22
pubmed: 19079156
Parasit Vectors. 2010 Mar 26;3(1):23
pubmed: 20338063
Genes Cells. 2002 Jul;7(7):619-27
pubmed: 12081640
Antioxid Redox Signal. 2017 Aug 29;:
pubmed: 28747072
Curr Opin Immunol. 2007 Aug;19(4):376-84
pubmed: 17702556
Cell. 2001 Jul 27;106(2):157-69
pubmed: 11511344
Cell Physiol Biochem. 2012;30(4):815-26
pubmed: 22890197
Cell Death Differ. 2009 Aug;16(8):1126-34
pubmed: 19325569
Infect Immun. 2012 Jan;80(1):143-9
pubmed: 22083705
Trans R Soc Trop Med Hyg. 1998 Nov-Dec;92(6):593-6
pubmed: 10326098
Curr Genet. 2016 May;62(2):295-300
pubmed: 26589893
J Cell Biol. 1985 Dec;101(6):2210-22
pubmed: 3905822
Genomics. 1992 Dec;14(4):897-911
pubmed: 1478671
Biochim Biophys Acta. 1995 Apr 24;1270(2-3):207-10
pubmed: 7727545
Semin Cell Dev Biol. 2015 Sep;45:24-31
pubmed: 26519113
Trends Cell Biol. 2000 Aug;10(8):316-21
pubmed: 10884683
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3185-90
pubmed: 11248053
J Biol Chem. 1989 Apr 5;264(10):5358-63
pubmed: 2538416
Curr Opin Gastroenterol. 2015 Jan;31(1):38-44
pubmed: 25394233
Parasitol Res. 2006 Feb;98(3):179-83
pubmed: 16374616
J Biol Chem. 2011 May 20;286(20):17982-91
pubmed: 21454475
Immunity. 1999 Oct;11(4):391-8
pubmed: 10549621
J Cell Biol. 2008 Mar 10;180(5):905-14
pubmed: 18316410
J Cell Sci. 2004 Jul 15;117(Pt 16):3625-34
pubmed: 15252130
Nat Immunol. 2005 Jun;6(6):551-7
pubmed: 15908936
J Pharmacol Exp Ther. 2017 Feb;360(2):378-387
pubmed: 27980039
Cell Signal. 2012 Mar;24(3):677-84
pubmed: 22101012
Biochim Biophys Acta. 2006 Dec;1758(12):1893-901
pubmed: 16938269
Arch Med Res. 2006 Feb;37(2):221-5
pubmed: 16380322
Parasitology. 1995 Dec;111 ( Pt 5):569-74
pubmed: 8559589
J Biol Chem. 2001 Nov 30;276(48):44976-83
pubmed: 11579092
Biochim Biophys Acta. 2009 Aug;1788(8):1570-81
pubmed: 19046939
Mol Biochem Parasitol. 2003 Jul;129(2):137-46
pubmed: 12850258
J Cell Physiol. 1991 Mar;146(3):362-9
pubmed: 1902481
PLoS Pathog. 2013;9(8):e1003489
pubmed: 23990778
J Biol Chem. 1996 Aug 2;271(31):18431-6
pubmed: 8702487
Nat Rev Mol Cell Biol. 2005 Jun;6(6):499-505
pubmed: 15928713
Nature. 2005 Feb 24;433(7028):865-8
pubmed: 15729342
J Proteomics. 2015 Jan 1;112:125-40
pubmed: 25109464
Front Immunol. 2016 May 12;7:175
pubmed: 27242782
J Biol Chem. 1991 Dec 25;266(36):24849-58
pubmed: 1761578
Exp Parasitol. 2018 Apr;187:86-92
pubmed: 29476758
Parasitol Int. 2008 Dec;57(4):417-23
pubmed: 18571975
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Annu Rev Microbiol. 2014;68:493-520
pubmed: 25002094
Med Sci Monit. 2003 Jun;9(6):BR225-30
pubmed: 12824945
J Parasitol. 1982 Jun;68(3):372-7
pubmed: 6284905
Cell Microbiol. 2007 Jul;9(7):1796-808
pubmed: 17359234
Trans R Soc Trop Med Hyg. 1978;72(4):431-2
pubmed: 212851
PLoS One. 2016 Mar 30;11(3):e0152583
pubmed: 27028538
Infect Immun. 1994 May;62(5):1534-41
pubmed: 7513301
Exp Parasitol. 2015 Jul;154:33-42
pubmed: 25889553
Traffic. 2007 Aug;8(8):951-8
pubmed: 17547702
Antimicrob Agents Chemother. 1990 Sep;34(9):1824-6
pubmed: 2285300
Protein Sci. 1996 Dec;5(12):2459-67
pubmed: 8976554
Cells. 2017 Nov 21;6(4):
pubmed: 29160807
J Cell Biol. 1995 Dec;131(6 Pt 2):1737-45
pubmed: 8557741
Nature. 2002 Jan 24;415(6870):389-95
pubmed: 11807545
Trends Parasitol. 2011 Jun;27(6):254-63
pubmed: 21440507
Annu Rev Cell Dev Biol. 2003;19:697-731
pubmed: 14570587
Exp Parasitol. 2010 Jul;125(3):279-85
pubmed: 20138872
FEBS Lett. 2010 May 3;584(9):1895-900
pubmed: 19944693
Rev Latinoam Microbiol. 2006 Apr-Jun;48(2):70-2
pubmed: 17578075
Nat Med. 2003 Mar;9(3):322-30
pubmed: 12563314
PLoS Pathog. 2016 Aug 30;12(8):e1005853
pubmed: 27575775
J Biol Chem. 1999 Nov 5;274(45):32445-52
pubmed: 10542289
J Cell Biol. 2010 Jun 14;189(6):1027-38
pubmed: 20530211
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16783-7
pubmed: 20837548
Mol Immunol. 2007 Jan;44(1-3):33-43
pubmed: 16908067
Infect Immun. 1985 May;48(2):292-7
pubmed: 2580787
Cell Signal. 2000 Feb;12(2):81-90
pubmed: 10679576
J Infect Dis. 1981 Jan;143(1):83-93
pubmed: 6260869
J Cell Biol. 2002 Nov 25;159(4):625-35
pubmed: 12438417
J Biol Chem. 2003 Aug 29;278(35):32744-52
pubmed: 12801930
Parasitol Today. 1997 May;13(5):178-83
pubmed: 15275088