Comprehensive analysis of the secreted proteome of adult Necator americanus hookworms.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
17
11
2019
accepted:
18
03
2020
revised:
05
06
2020
pubmed:
27
5
2020
medline:
17
7
2020
entrez:
27
5
2020
Statut:
epublish
Résumé
The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a number of animal hookworm species, but until now, the difficulty in obtaining sufficient live N. americanus has been an obstacle in characterizing the secretome of this important human pathogen. Herein we describe the ES proteome of N. americanus and utilize this information along with RNA Seq data to conduct the first proteogenomic analysis of a parasitic helminth, significantly improving the available genome and thereby generating a robust description of the parasite secretome. The genome annotation resulted in a revised prediction of 3,425 fewer genes than initially reported, accompanied by a significant increase in the number of exons and introns, total gene length and the percentage of the genome covered by genes. Almost 200 ES proteins were identified by LC-MS/MS with SCP/TAPS proteins, 'hypothetical' proteins and proteases among the most abundant families. These proteins were compared to commonly used model species of human parasitic infections, including Ancylostoma caninum, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. SCP/TAPS proteins are immunogenic in nematode infections, so we expressed four of those identified in this study in recombinant form and showed that they are all recognized to varying degrees by serum antibodies from hookworm-infected subjects from a disease-endemic area of Brazil. Our findings provide valuable information on important families of proteins with both known and unknown functions that could be instrumental in host-parasite interactions, including protein families that might be key for parasite survival in the onslaught of robust immune responses, as well as vaccine and diagnostic targets.
Identifiants
pubmed: 32453752
doi: 10.1371/journal.pntd.0008237
pii: PNTD-D-19-01849
pmc: PMC7274458
doi:
Substances chimiques
Helminth Proteins
0
Proteome
0
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
e0008237Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM097435
Pays : United States
Déclaration de conflit d'intérêts
Srikanth S. Manda, is employed by LifeBytes India Pvt Ltd. Dr Manda declares his affiliation to this company and has no competing interests of relevance to this manuscript. The authors have declared that no competing interests exist.
Références
Vaccine. 2008 May 2;26(19):2408-17
pubmed: 18396361
Sci Transl Med. 2016 Oct 26;8(362):362ra143
pubmed: 27797959
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
PLoS Negl Trop Dis. 2017 May 2;11(5):e0005574
pubmed: 28464026
Nat Genet. 2015 Apr;47(4):416-22
pubmed: 25730766
J Immunol. 2004 Aug 15;173(4):2699-704
pubmed: 15294988
Mob DNA. 2015 Jun 02;6:11
pubmed: 26045719
Vaccine. 2005 May 2;23(24):3123-30
pubmed: 15837211
Nucleic Acids Res. 2015 Jan;43(Database issue):D698-706
pubmed: 25392426
Biotechnol Adv. 2009 Jul-Aug;27(4):376-88
pubmed: 19239923
Adv Exp Med Biol. 2011;712:155-76
pubmed: 21660664
Mol Pharmacol. 1999 Nov;56(5):926-32
pubmed: 10531396
Trends Parasitol. 2018 Mar;34(3):179-183
pubmed: 29249363
Plant Physiol. 2014 Feb;164(2):513-24
pubmed: 24306534
J Extracell Vesicles. 2018 Jan 21;7(1):1428004
pubmed: 29410780
Bioinformatics. 2003 Feb 12;19(3):390-5
pubmed: 12584125
PLoS Negl Trop Dis. 2010 May 11;4(5):e684
pubmed: 20485481
Bioinformatics. 2008 Mar 1;24(5):637-44
pubmed: 18218656
J Infect Dis. 2009 Mar 15;199(6):904-12
pubmed: 19434933
Nat Protoc. 2007;2(4):953-71
pubmed: 17446895
Mol Cell Proteomics. 2009 Jan;8(1):109-21
pubmed: 18753127
Exp Parasitol. 2002 Jun-Jul;101(2-3):83-9
pubmed: 12427461
PLoS Med. 2007 Jan;4(1):e14
pubmed: 17214506
Immunity. 2018 Nov 20;49(5):801-818
pubmed: 30462997
Int J Parasitol. 2006 May 31;36(6):701-10
pubmed: 16545815
Ann N Y Acad Sci. 2008;1136:38-44
pubmed: 17954674
Genome Res. 2010 Jun;20(6):837-46
pubmed: 20237107
Trends Parasitol. 2017 Nov;33(11):875-888
pubmed: 28734897
PLoS Negl Trop Dis. 2012 Jan;6(1):e1455
pubmed: 22253936
Bioinformatics. 2014 May 1;30(9):1236-40
pubmed: 24451626
BMC Bioinformatics. 2011 Dec 22;12:491
pubmed: 22192575
Parasit Vectors. 2018 Jan 25;11(1):59
pubmed: 29370855
Proteomics. 2004 Jan;4(1):59-77
pubmed: 14730672
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Mol Biochem Parasitol. 2008 Aug;160(2):90-9
pubmed: 18501979
FASEB J. 2005 Oct;19(12):1743-5
pubmed: 16037096
Curr Protoc Bioinformatics. 2014 Dec 12;48:4.11.1-39
pubmed: 25501943
J Immunol. 2000 Dec 1;165(11):6447-53
pubmed: 11086084
Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60
pubmed: 10677483
Nat Methods. 2014 Nov;11(11):1114-25
pubmed: 25357241
Infect Immun. 2006 Feb;74(2):961-7
pubmed: 16428741
Proteomics. 2017 Dec;17(23-24):
pubmed: 29052354
Nat Rev Dis Primers. 2016 Dec 08;2:16088
pubmed: 27929101
J Parasitol. 1992 Oct;78(5):917-9
pubmed: 1403440
Bioinformatics. 2015 Oct 1;31(19):3210-2
pubmed: 26059717
Inflamm Bowel Dis. 2011 Nov;17(11):2275-86
pubmed: 21290484
Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169
pubmed: 27899622
J Proteomics. 2011 Aug 24;74(9):1573-94
pubmed: 21722761
Lancet. 2012 Dec 15;380(9859):2197-223
pubmed: 23245608
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
Genome Res. 2009 Sep;19(9):1639-45
pubmed: 19541911
PLoS One. 2011;6(7):e21800
pubmed: 21789182
J Extracell Vesicles. 2014 Dec 22;3:25040
pubmed: 25536932
Methods Mol Biol. 2018;1757:371-397
pubmed: 29761465
Mol Biochem Parasitol. 2016 Jul;208(1):33-40
pubmed: 27297184
Nat Genet. 2016 Mar;48(3):299-307
pubmed: 26829753
PLoS Negl Trop Dis. 2008 Sep 17;2(9):e291
pubmed: 18820740
PLoS Med. 2005 Mar;2(3):e67
pubmed: 15783256
Bioinformatics. 2007 Jan 1;23(1):127-8
pubmed: 17050570
Bioinformatics. 2005 Sep 15;21(18):3674-6
pubmed: 16081474
PLoS Med. 2005 Oct;2(10):e295
pubmed: 16231975
Mol Cell Proteomics. 2013 Sep;12(9):2383-93
pubmed: 23720762
Nat Genet. 2014 Mar;46(3):261-269
pubmed: 24441737
Nat Rev Microbiol. 2010 Nov;8(11):814-26
pubmed: 20948553
J Mol Biol. 2001 Jan 19;305(3):567-80
pubmed: 11152613
Nucleic Acids Res. 2014 Sep;42(15):e119
pubmed: 24990371
Vaccine. 2013 Apr 18;31 Suppl 2:B227-32
pubmed: 23598487
Parasite Immunol. 2005 Apr;27(4):139-46
pubmed: 15910422
Bioinformatics. 2017 Sep 15;33(18):2938-2940
pubmed: 28645171
Lancet. 2004 Sep 11-17;364(9438):981-3
pubmed: 15364190
Parasitology. 2015 Feb;142 Suppl 1:S85-97
pubmed: 25482650
Bioinformatics. 2016 Mar 1;32(5):767-9
pubmed: 26559507
PLoS Negl Trop Dis. 2018 Aug 23;12(8):e0005840
pubmed: 30138310
Front Immunol. 2018 Apr 30;9:850
pubmed: 29760697
Prev Vet Med. 2000 May 30;45(1-2):23-41
pubmed: 10802332
Mol Biochem Parasitol. 2017 Jul;215:2-10
pubmed: 27899279
PLoS Negl Trop Dis. 2012;6(2):e1522
pubmed: 22347515
N Engl J Med. 2004 Aug 19;351(8):799-807
pubmed: 15317893
Vaccine. 2016 Jun 3;34(26):3001-3005
pubmed: 27040400
Exp Parasitol. 2003 Nov-Dec;105(3-4):192-200
pubmed: 14990312
FASEB J. 2002 Sep;16(11):1458-60
pubmed: 12205047
Mol Biochem Parasitol. 2009 Sep;167(1):1-11
pubmed: 19406170
PLoS Pathog. 2013 Aug;9(8):e1003492
pubmed: 23966853
BMC Genomics. 2010 May 14;11:307
pubmed: 20470405
Mol Cell Proteomics. 2014 Oct;13(10):2736-51
pubmed: 24994561
PLoS Negl Trop Dis. 2012;6(10):e1856
pubmed: 23071854