Higher genome variability within metabolism genes associates with recurrent Clostridium difficile infection.
Amino Acids
/ metabolism
Carbon
/ metabolism
Clostridioides difficile
/ classification
Clostridium Infections
/ microbiology
Cross Infection
/ microbiology
Genetic Variation
Genome, Bacterial
/ genetics
Humans
Metabolic Networks and Pathways
/ genetics
Oxidative Phosphorylation
Prophages
/ genetics
Reinfection
/ microbiology
Retrospective Studies
Virulence
Whole Genome Sequencing
Clostridium difficile
Infection
Prophage
Recurrence
Whole genome sequencing
Journal
BMC microbiology
ISSN: 1471-2180
Titre abrégé: BMC Microbiol
Pays: England
ID NLM: 100966981
Informations de publication
Date de publication:
28 01 2021
28 01 2021
Historique:
received:
15
10
2020
accepted:
08
01
2021
entrez:
29
1
2021
pubmed:
30
1
2021
medline:
25
2
2023
Statut:
epublish
Résumé
Clostridium difficile (C. difficile) is a major source of healthcare-associated infection with a high risk of recurrence, attributable to many factors such as usage of antibiotics, older age and immunocompromised status of the patients. C. difficile has also a highly diverse genome, which may contribute to its high virulence. Herein we examined whether the genome conservation, measured as non-synonymous to synonymous mutations ratio (dN/dS) in core genes, presence of single genes, plasmids and prophages increased the risk of reinfection in a subset of 134 C. difficile isolates from our previous study in a singly hemato-oncology ward. C. difficile isolates were subjected to whole-genome sequencing (WGS) on Ion Torrent PGM sequencer. Genomes were assembled with MIRA5 and annotated with prokka and VRprofile. Logistic regression was used to asses the relationship between single gene presence and the odds of infection recurrence. DN/dS ratios were computed with codeml. Functional annotation was conducted with eggNOG-Mapper. We have found that the presence of certain genes, associated with carbon metabolism and oxidative phosphorylation, increased the odds of infection recurrence. More core genes were under positive selective pressure in recurrent disease isolates - they were mostly associated with the metabolism of aminoacids. Finally, prophage elements were more prevalent in single infection isolates and plasmids did not influence the odds of recurrence. Our findings suggest higher genetic plasticity in isolates causing recurrent infection, associated mainly with metabolism. On the other hand, the presence of prophages seems to reduce the isolates' virulence.
Sections du résumé
BACKGROUND
Clostridium difficile (C. difficile) is a major source of healthcare-associated infection with a high risk of recurrence, attributable to many factors such as usage of antibiotics, older age and immunocompromised status of the patients. C. difficile has also a highly diverse genome, which may contribute to its high virulence. Herein we examined whether the genome conservation, measured as non-synonymous to synonymous mutations ratio (dN/dS) in core genes, presence of single genes, plasmids and prophages increased the risk of reinfection in a subset of 134 C. difficile isolates from our previous study in a singly hemato-oncology ward.
METHODS
C. difficile isolates were subjected to whole-genome sequencing (WGS) on Ion Torrent PGM sequencer. Genomes were assembled with MIRA5 and annotated with prokka and VRprofile. Logistic regression was used to asses the relationship between single gene presence and the odds of infection recurrence. DN/dS ratios were computed with codeml. Functional annotation was conducted with eggNOG-Mapper.
RESULTS
We have found that the presence of certain genes, associated with carbon metabolism and oxidative phosphorylation, increased the odds of infection recurrence. More core genes were under positive selective pressure in recurrent disease isolates - they were mostly associated with the metabolism of aminoacids. Finally, prophage elements were more prevalent in single infection isolates and plasmids did not influence the odds of recurrence.
CONCLUSIONS
Our findings suggest higher genetic plasticity in isolates causing recurrent infection, associated mainly with metabolism. On the other hand, the presence of prophages seems to reduce the isolates' virulence.
Identifiants
pubmed: 33509087
doi: 10.1186/s12866-021-02090-9
pii: 10.1186/s12866-021-02090-9
pmc: PMC7842062
doi:
Substances chimiques
Amino Acids
0
Carbon
7440-44-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
36Références
Ann Gastroenterol. 2016 Apr-Jun;29(2):147-54
pubmed: 27065726
J Med Microbiol. 2005 Feb;54(Pt 2):129-135
pubmed: 15673505
PLoS One. 2016 Jun 28;11(6):e0158204
pubmed: 27351947
J Clin Microbiol. 2016 Jan;54(1):13-8
pubmed: 26511734
mBio. 2015 Jun 02;6(3):e00551
pubmed: 26037121
JAMA. 2015 Jan 27;313(4):398-408
pubmed: 25626036
Gut Liver. 2019 Jan 15;13(1):16-24
pubmed: 30400734
Anaerobe. 2016 Aug;40:95-9
pubmed: 27370902
Clin Infect Dis. 2019 May 30;68(12):2144-2153
pubmed: 30281082
Clin Microbiol Infect. 2014 Mar;20 Suppl 2:1-26
pubmed: 24118601
PeerJ. 2018 Apr 2;6:e4588
pubmed: 29629246
Microb Genom. 2019 Sep;5(9):
pubmed: 31526450
J Integr Bioinform. 2018 Jul 3;15(3):
pubmed: 30218604
J Clin Microbiol. 2011 Jun;49(6):2230-8
pubmed: 21508155
Infect Control Hosp Epidemiol. 2015 Apr;36(4):452-60
pubmed: 25626326
Genome Announc. 2015 Mar 26;3(2):
pubmed: 25814591
J Bacteriol. 2007 Nov;189(22):8186-95
pubmed: 17675389
Braz J Infect Dis. 2012 May-Jun;16(3):256-61
pubmed: 22729193
Front Microbiol. 2019 Feb 15;10:219
pubmed: 30828322
Nucleic Acids Res. 2014 Jan;42(Database issue):D199-205
pubmed: 24214961
Bioinformatics. 2015 Nov 15;31(22):3691-3
pubmed: 26198102
Int J Adv Life Sci. 2012;4(1-2):21-32
pubmed: 24151543
Clin Infect Dis. 2015 Dec 15;61(12):1781-8
pubmed: 26338788
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Nat Genet. 2006 Jul;38(7):779-86
pubmed: 16804543
Chem Biol. 2014 Nov 20;21(11):1423-32
pubmed: 25442374
Nat Rev Microbiol. 2004 Feb;2(2):123-40
pubmed: 15040260
J Bacteriol. 2009 Jun;191(12):3881-91
pubmed: 19376880
Bioinformatics. 2015 Dec 15;31(24):3997-9
pubmed: 26315911
Mol Biol Evol. 2007 Aug;24(8):1586-91
pubmed: 17483113
Genome Biol. 2012 Dec 21;13(12):R118
pubmed: 23259504
Lancet Infect Dis. 2005 Sep;5(9):549-57
pubmed: 16122678
FEMS Microbiol Rev. 2008 May;32(3):541-55
pubmed: 18397287
Clin Infect Dis. 2005 Jun 1;40(11):1591-7
pubmed: 15889355
Appl Environ Microbiol. 2013 Oct;79(20):6236-43
pubmed: 23913427
Front Microbiol. 2018 Aug 31;9:2033
pubmed: 30233520
Am J Health Syst Pharm. 2019 Apr 17;76(9):581-590
pubmed: 31361830
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W609-12
pubmed: 16845082
J Hosp Infect. 2008 Dec;70(4):298-304
pubmed: 18951661
Genome Biol Evol. 2018 Mar 1;10(3):982-998
pubmed: 29617810
J Virol. 2009 Dec;83(23):12037-45
pubmed: 19776116
Microbiology (Reading). 1996 Apr;142 ( Pt 4):907-14
pubmed: 8936317
Nat Genet. 2019 Sep;51(9):1315-1320
pubmed: 31406348
J Clin Med Res. 2019 Jul;11(7):465-471
pubmed: 31236163
Lancet. 2011 Jan 1;377(9759):63-73
pubmed: 21084111
J Biotechnol. 2017 May 20;250:23-28
pubmed: 28216103
Mol Microbiol. 2002 Oct;46(2):439-52
pubmed: 12406220
Front Microbiol. 2020 Jul 20;11:1618
pubmed: 32793147
mBio. 2015 Feb 24;6(2):e02383
pubmed: 25714712
N Engl J Med. 2015 Apr 16;372(16):1539-48
pubmed: 25875259
J Theor Biol. 2006 Mar 21;239(2):226-35
pubmed: 16239014
Genome Biol. 2009;10(9):R102
pubmed: 19781061
PLoS One. 2010 Dec 08;5(12):e15147
pubmed: 21170335
PLoS One. 2013 Apr 23;8(4):e62157
pubmed: 23626782
Biochem J. 1934;28(5):1746-59
pubmed: 16745572
Eur J Clin Microbiol Infect Dis. 2019 Jul;38(7):1211-1221
pubmed: 30945014
J Microbiol Biotechnol. 2010 Jan;20(1):5-14
pubmed: 20134227
Clin Infect Dis. 2012 Aug;55 Suppl 2:S77-87
pubmed: 22752869
Genome Res. 2004 Jun;14(6):1147-59
pubmed: 15140833
J Bacteriol. 2011 Jun;193(11):2726-34
pubmed: 21441508
Clin Microbiol Rev. 2015 Jul;28(3):721-41
pubmed: 26085550
J Bacteriol. 2012 Apr;194(8):2125-6
pubmed: 22461557
Appl Environ Microbiol. 2012 Nov;78(21):7662-70
pubmed: 22923402
BMC Microbiol. 2018 May 31;18(1):46
pubmed: 29855259
Nat Commun. 2020 Jan 30;11(1):598
pubmed: 32001686
Int J Infect Dis. 2020 Jan;90:237-242
pubmed: 31672656
Microbiol Rev. 1988 Dec;52(4):433-51
pubmed: 3070319
Gut Microbes. 2010 Jan;1(1):58-64
pubmed: 20664812
Proc Natl Acad Sci U S A. 2019 May 14;116(20):10072-10080
pubmed: 31036669
Genetics. 2006 Apr;172(4):2665-81
pubmed: 16489234
Front Microbiol. 2018 Aug 21;9:1970
pubmed: 30186274
Plasmid. 2018 Mar - May;96-97:25-38
pubmed: 29702124
J Infect Dis. 1988 Oct;158(4):731-6
pubmed: 2844914
Brief Bioinform. 2018 Jul 20;19(4):566-574
pubmed: 28077405
Front Microbiol. 2018 Jul 31;9:1701
pubmed: 30108562
Gut Microbes. 2010 Jul;1(4):269-276
pubmed: 21327033
Nucleic Acids Res. 2005 Nov 07;33(19):6445-58
pubmed: 16275786
Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7527-32
pubmed: 20368420
Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
pubmed: 7984417
J Infect Dis. 1987 Dec;156(6):1036-8
pubmed: 3680990
Bioinformatics. 2014 Jul 15;30(14):2068-9
pubmed: 24642063
Mol Biol Evol. 2017 Aug 1;34(8):2115-2122
pubmed: 28460117
Nucleic Acids Res. 2019 Jan 8;47(D1):D309-D314
pubmed: 30418610