title: Lactobacillus paracasei comparative genomics: towards species pan-genome definition and exploitation of diversity.
abstract: Lactobacillus paracasei is a member of the normal human and animal gut microbiota and is used extensively in the food industry in starter cultures for dairy products or as probiotics. With the development of low-cost, high-throughput sequencing techniques it has become feasible to sequence many different strains of one species and to determine its "pan-genome". We have sequenced the genomes of 34 different L. paracasei strains, and performed a comparative genomics analysis. We analysed genome synteny and content, focussing on the pan-genome, core genome and variable genome. Each genome was shown to contain around 2800-3100 protein-coding genes, and comparative analysis identified over 4200 ortholog groups that comprise the pan-genome of this species, of which about 1800 ortholog groups make up the conserved core. Several factors previously associated with host-microbe interactions such as pili, cell-envelope proteinase, hydrolases p40 and p75 or the capacity to produce short branched-chain fatty acids (bkd operon) are part of the L. paracasei core genome present in all analysed strains. The variome consists mainly of hypothetical proteins, phages, plasmids, transposon/conjugative elements, and known functions such as sugar metabolism, cell-surface proteins, transporters, CRISPR-associated proteins, and EPS biosynthesis proteins. An enormous variety and variability of sugar utilization gene cassettes were identified, with each strain harbouring between 25-53 cassettes, reflecting the high adaptability of L. paracasei to different niches. A phylogenomic tree was constructed based on total genome contents, and together with an analysis of horizontal gene transfer events we conclude that evolution of these L. paracasei strains is complex and not always related to niche adaptation. The results of this genome content comparison was used, together with high-throughput growth experiments on various carbohydrates, to perform gene-trait matching analysis, in order to link the distribution pattern of a specific phenotype to the presence/absence of specific sets of genes.
authors.affiliation: Danone Research, Palaiseau, France.
authors.forename: Tamara
authors.initials: T
authors.lastname: Smokvina
authors.forename: Michiel
authors.initials: M
authors.lastname: Wels
authors.forename: Justyna
authors.initials: J
authors.lastname: Polka
authors.forename: Christian
authors.initials: C
authors.lastname: Chervaux
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
authors.forename: Jos
authors.initials: J
authors.lastname: Boekhorst
authors.forename: Johan E T
authors.initials: JE
authors.lastname: van Hylckama Vlieg
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Siezen
mesh_terms: D050260:Carbohydrate Metabolism / Q000235:genetics; D016000:Cluster Analysis; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D023061:Gene Order; D022761:Gene Transfer, Horizontal; D014644:Genetic Variation; D016680:Genome, Bacterial; D023281:Genomics; D007778:Lactobacillus / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics
chemical_list: D005227:Fatty Acids
references.citation: J Mol Biol. 2001 Dec 14;314(5):1041-52
references.pmid: 11743721
references.citation: Microbiology (Reading). 2007 Aug;153(Pt 8):2655-2665
references.pmid: 17660430
references.citation: Gut. 2000 Sep;47(3):397-403
references.pmid: 10940278
references.citation: J Mol Microbiol Biotechnol. 2010;19(4):231-41
references.pmid: 21178363
references.citation: Int J Syst Evol Microbiol. 2008 Jul;58(Pt 7):1764-5
references.pmid: 18599731
references.citation: J Bacteriol. 2012 Nov;194(21):5725-7
references.pmid: 22821969
references.citation: Nat Biotechnol. 2004 Dec;22(12):1554-8
references.pmid: 15543133
references.citation: FEMS Microbiol Rev. 2005 Aug;29(3):435-63
references.pmid: 16125007
references.citation: Environ Microbiol. 2010 Mar;12(3):758-73
references.pmid: 20002138
references.citation: Int J Food Microbiol. 2009 Apr 30;131(1):62-70
references.pmid: 18635282
references.citation: J Bacteriol. 2011 Jul;193(13):3419-20
references.pmid: 21515769
references.citation: Int J Med Microbiol. 2011 Dec;301(8):619-22
references.pmid: 22000739
references.citation: Microb Cell Fact. 2012 Feb 01;11:15
references.pmid: 22297095
references.citation: Curr Protoc Bioinformatics. 2011 Sep;Chapter 6:6.12.1-6.12.19
references.pmid: 21901743
references.citation: Int J Syst Bacteriol. 1996 Jan;46(1):337-40
references.pmid: 8573516
references.citation: Int Microbiol. 2010 Jun;13(2):45-57
references.pmid: 20890839
references.citation: Res Microbiol. 2004 Jun;155(5):376-86
references.pmid: 15207870
references.citation: J Bacteriol. 2007 Feb;189(4):1244-53
references.pmid: 16963569
references.citation: Appl Environ Microbiol. 2010 Apr;76(7):2049-57
references.pmid: 20118368
references.citation: Nat Rev Microbiol. 2010 Aug;8(8):552-63
references.pmid: 20601965
references.citation: Appl Environ Microbiol. 2012 Jan;78(1):185-93
references.pmid: 22020518
references.citation: Cell Host Microbe. 2012 Apr 19;11(4):387-96
references.pmid: 22520466
references.citation: Appl Environ Microbiol. 2013 Mar;79(6):1923-33
references.pmid: 23315726
references.citation: J Bacteriol. 2011 Jun;193(12):3160-1
references.pmid: 21478345
references.citation: Nucleic Acids Res. 1999 Dec 1;27(23):4636-41
references.pmid: 10556321
references.citation: Adv Biochem Eng Biotechnol. 2008;111:1-66
references.pmid: 18461293
references.citation: J Bacteriol. 2008 Feb;190(4):1401-12
references.pmid: 18065539
references.citation: FEMS Microbiol Rev. 1990 Sep;7(1-2):43-60
references.pmid: 2176796
references.citation: PLoS Genet. 2011 Feb;7(2):e1001314
references.pmid: 21379339
references.citation: Microb Biotechnol. 2011 May;4(3):383-402
references.pmid: 21338475
references.citation: Am J Clin Nutr. 2001 Feb;73(2 Suppl):451S-455S
references.pmid: 11157356
references.citation: J Bacteriol. 2005 Sep;187(17):6119-27
references.pmid: 16109953
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1990-5
references.pmid: 12566566
references.citation: Molecules. 2009 Jul 13;14(7):2535-54
references.pmid: 19633622
references.citation: J Bacteriol. 2010 May;192(10):2647-8
references.pmid: 20348264
references.citation: Eur J Clin Nutr. 2008 Feb;62(2):225-31
references.pmid: 17327863
references.citation: Appl Environ Microbiol. 2011 Feb;77(3):954-65
references.pmid: 21131523
references.citation: Microb Cell Fact. 2011 Aug 30;10 Suppl 1:S3
references.pmid: 21995294
references.citation: Br J Nutr. 2010 Jan;103(1):58-68
references.pmid: 19747410
references.citation: BMC Genomics. 2006 May 24;7:126
references.pmid: 16723015
references.citation: Nat Struct Biol. 1997 Oct;4(10):833-8
references.pmid: 9334749
references.citation: Int J Syst Evol Microbiol. 2012 Oct;62(Pt 10):2546-2548
references.pmid: 23042764
references.citation: J Biol Chem. 2002 Dec 27;277(52):50959-65
references.pmid: 12393915
references.citation: Biochim Biophys Acta. 2004 Nov 11;1694(1-3):269-78
references.pmid: 15546671
references.citation: Microb Ecol. 2010 Nov;60(4):708-20
references.pmid: 20623278
references.citation: Trends Microbiol. 2009 Aug;17(8):337-8
references.pmid: 19660950
references.citation: Science. 2010 Jan 8;327(5962):167-70
references.pmid: 20056882
references.citation: Curr Opin Microbiol. 2009 Feb;12(1):4-10
references.pmid: 19155186
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13950-5
references.pmid: 16172379
references.citation: Appl Environ Microbiol. 2007 Oct;73(20):6601-11
references.pmid: 17704267
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3906-12
references.pmid: 15671160
references.citation: Appl Environ Microbiol. 2008 Aug;74(15):4703-10
references.pmid: 18539806
references.citation: Carcinogenesis. 1999 Apr;20(4):629-34
references.pmid: 10223191
references.citation: Bioinformatics. 2002 Jan;18(1):207-8
references.pmid: 11836235
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17193-8
references.pmid: 19805152
references.citation: J Altern Complement Med. 2010 Sep;16(9):989-93
references.pmid: 20738164
references.citation: BMC Genomics. 2008 Feb 08;9:75
references.pmid: 18261238
references.citation: Nucleic Acids Res. 2003 Mar 15;31(6):1780-9
references.pmid: 12626720
references.citation: BMC Genomics. 2010 Jan 15;11:36
references.pmid: 20078865
references.citation: J Bacteriol. 1999 Sep;181(17):5433-42
references.pmid: 10464218
references.citation: Trends Microbiol. 2002 May;10(5):209-12
references.pmid: 11973144
references.citation: J Bacteriol. 2000 Jan;182(1):155-63
references.pmid: 10613875
references.citation: FEMS Microbiol Lett. 2009 Mar;292(1):1-6
references.pmid: 19087207
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2512-7
references.pmid: 14983040
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6718-23
references.pmid: 16617113
references.citation: Antonie Van Leeuwenhoek. 2011 Feb;99(2):127-31
references.pmid: 20852931
references.citation: Antonie Van Leeuwenhoek. 1983 Sep;49(3):259-74
references.pmid: 6312881
references.citation: Trends Microbiol. 2009 Apr;17(4):139-45
references.pmid: 19299134
references.citation: J Bacteriol. 2011 Sep;193(18):5023
references.pmid: 21868802
references.citation: Antonie Van Leeuwenhoek. 1996 Oct;70(2-4):161-83
references.pmid: 8879406
references.citation: Gastroenterology. 2006 Feb;130(2 Suppl 1):S100-5
references.pmid: 16473056
references.citation: J Bacteriol. 2005 Jun;187(11):3878-83
references.pmid: 15901716
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: Epidemiol Infect. 2011 Jun;139(6):919-26
references.pmid: 20670468
references.citation: PLoS One. 2013;8(3):e59239
references.pmid: 23527145
references.citation: PLoS One. 2012;7(2):e31588
references.pmid: 22359601
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000507
references.pmid: 19876390
references.citation: Nat Rev Microbiol. 2010 Sep;8(9):623-33
references.pmid: 20676145
references.citation: Int J Syst Evol Microbiol. 2002 Jan;52(Pt 1):285-287
references.pmid: 11837314
references.citation: FEMS Microbiol Rev. 1993 Sep;12(1-3):179-206
references.pmid: 8398214
references.citation: BMC Genomics. 2010 Nov 23;11:651
references.pmid: 21092245
references.citation: Eur J Gastroenterol Hepatol. 2000 Oct;12(10):1077-88
references.pmid: 11057452
references.citation: Trends Microbiol. 2009 Aug;17(8):338-40
references.pmid: 19674902
references.citation: mBio. 2012 Mar 01;3(1):e00318-11
references.pmid: 22354958
references.citation: BMC Genomics. 2012 Aug 03;13:373
references.pmid: 22863143
references.citation: BMC Bioinformatics. 2010 Mar 08;11:119
references.pmid: 20211023
references.citation: J Bacteriol. 2005 Oct;187(19):6750-61
references.pmid: 16166538
references.citation: J Am Coll Nutr. 2010 Oct;29(5):455-68
references.pmid: 21504972
references.citation: BMC Genomics. 2012 May 04;13:170
references.pmid: 22559291
references.citation: Curr Protoc Bioinformatics. 2003 May;Chapter 4:Unit4.5
references.pmid: 18428700
references.citation: Vaccine. 2009 Sep 18;27(41):5677-84
references.pmid: 19615959
references.citation: BMC Microbiol. 2013 Mar 26;13:68
references.pmid: 23530958
references.citation: Microb Ecol. 2011 Oct;62(3):487-504
references.pmid: 21643699
references.citation: Proteins. 2007 May 15;67(3):681-94
references.pmid: 17348030
references.citation: Genome Biol Evol. 2009 Jul 14;1:239-57
references.pmid: 20333194
references.citation: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references.pmid: 15034147
references.citation: J Bacteriol. 2010 Oct;192(19):5268-9
references.pmid: 20675486
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15611-6
references.pmid: 17030793
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9274-9
references.pmid: 16754859
references.citation: J Bacteriol. 2008 Jan;190(2):727-35
references.pmid: 17993529
references.citation: Curr Opin Genet Dev. 2005 Dec;15(6):589-94
references.pmid: 16185861