Pyrosequencing-based comparative genome analysis of the nosocomial pathogen Enterococcus faecium and identification of a large transferable pathogenicity island.
BACKGROUND
The Gram-positive bacterium Enterococcus faecium is an important cause of nosocomial infections in immunocompromized patients.


RESULTS
We present a pyrosequencing-based comparative genome analysis of seven E. faecium strains that were isolated from various sources. In the genomes of clinical isolates several antibiotic resistance genes were identified, including the vanA transposon that confers resistance to vancomycin in two strains. A functional comparison between E. faecium and the related opportunistic pathogen E. faecalis based on differences in the presence of protein families, revealed divergence in plant carbohydrate metabolic pathways and oxidative stress defense mechanisms. The E. faecium pan-genome was estimated to be essentially unlimited in size, indicating that E. faecium can efficiently acquire and incorporate exogenous DNA in its gene pool. One of the most prominent sources of genomic diversity consists of bacteriophages that have integrated in the genome. The CRISPR-Cas system, which contributes to immunity against bacteriophage infection in prokaryotes, is not present in the sequenced strains. Three sequenced isolates carry the esp gene, which is involved in urinary tract infections and biofilm formation. The esp gene is located on a large pathogenicity island (PAI), which is between 64 and 104 kb in size. Conjugation experiments showed that the entire esp PAI can be transferred horizontally and inserts in a site-specific manner.


CONCLUSIONS
Genes involved in environmental persistence, colonization and virulence can easily be aquired by E. faecium. This will make the development of successful treatment strategies targeted against this organism a challenge for years to come.
van Schaik
Willem
W
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. w.vanschaik@umcutrecht.nl
Top
Janetta
J
Riley
David R
DR
Boekhorst
Jos
J
Vrijenhoek
Joyce E P
JE
Schapendonk
Claudia M E
CM
Hendrickx
Antoni P A
AP
Nijman
Isaäc J
IJ
Bonten
Marc J M
MJ
Tettelin
Hervé
H
Willems
Rob J L
RJ
D001435:Bacteriophages / Q000235:genetics / Q000648:ultrastructure; D001483:Base Sequence; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000235:genetics* / Q000472:pathogenicity / Q000821:virology; D016680:Genome, Bacterial; D044404:Genomic Islands; D046529:Microscopy, Electron, Transmission; D010802:Phylogeny; D014774:Virulence
Nucleic Acids Res. 2001 Jan 1;29(1):41-3
11125044
Curr Opin Microbiol. 2006 Oct;9(5):454-60
16880002
Infect Control Hosp Epidemiol. 2008 Nov;29(11):996-1011
18947320
J Clin Microbiol. 2006 Mar;44(3):1059-64
16517894
BMC Microbiol. 2007 Apr 12;7:30
17430587
Int J Food Microbiol. 2009 Apr 30;131(1):62-70
18635282
N Engl J Med. 2009 Jan 29;360(5):439-43
19179312
Appl Environ Microbiol. 1997 May;63(5):1939-44
9143125
J Bacteriol. 1963 Dec;86:1275-82
14086101
Future Microbiol. 2009 Nov;4(9):1125-35
19895216
Genes Dev. 2007 Mar 1;21(5):601-14
17344419
J Infect Dis. 2003 Feb 1;187(3):508-12
12552437
J Clin Microbiol. 1990 Sep;28(9):2059-63
1977766
Antimicrob Agents Chemother. 1990 Aug;34(8):1565-9
2171424
J Vet Med B Infect Dis Vet Public Health. 2004 Oct-Nov;51(8-9):370-3
15525368
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5890-5
11983890
Microbiology (Reading). 2005 Sep;151(Pt 9):3019-3025
16151212
Antonie Van Leeuwenhoek. 1983 Sep;49(3):209-24
6354079
Plasmid. 2008 Jul;60(1):75-85
18511120
J Bacteriol. 2007 Nov;189(22):8233-40
17827282
FEMS Immunol Med Microbiol. 2010 Mar;58(2):254-68
20015231
Microbiol Mol Biol Rev. 2003 Jun;67(2):238-76, table of contents
12794192
Emerg Infect Dis. 2005 Jun;11(6):821-8
15963275
Antimicrob Agents Chemother. 1989 Jan;33(1):10-5
2523687
PLoS Pathog. 2007 Jan;3(1):e7
17257059
J Infect Dis. 2009 Oct 1;200(7):1162-5
19702507
J Biol Chem. 2000 Sep 29;275(39):30019-28
10862622
Lancet. 2001 Mar 17;357(9259):853-5
11265956
J Clin Microbiol. 2002 Jun;40(6):1963-71
12037049
Nucleic Acids Res. 1999 Dec 1;27(23):4636-41
10556321
J Mol Microbiol Biotechnol. 2007;13(1-3):140-6
17693721
Emerg Infect Dis. 2001 Jan-Feb;7(1):82-91
11266298
Euro Surveill. 2008 Nov 20;13(47):
19021959
J Mol Biol. 2004 Jul 16;340(4):783-95
15223320
Appl Environ Microbiol. 2009 Jul;75(14):4904-8
19447948
Microbiology (Reading). 2008 Oct;154(Pt 10):3199-3211
18832325
Mol Microbiol. 2001 Nov;42(3):729-40
11722738
J Bacteriol. 2007 Nov;189(22):8321-32
17873043
Nucleic Acids Res. 2003 Jul 1;31(13):3795-8
12824421
Science. 2003 Mar 28;299(5615):2071-4
12663927
J Antimicrob Chemother. 2004 Jul;54(1):232-5
15192049
Antimicrob Agents Chemother. 1999 Mar;43(3):483-91
10049255
Science. 2008 Dec 19;322(5909):1843-5
19095942
Emerg Infect Dis. 2003 Sep;9(9):1108-15
14519248
J Bacteriol. 1993 Jan;175(1):117-27
8380148
J Appl Microbiol. 2001 Aug;91(2):268-78
11473591
J Clin Microbiol. 2005 Jan;43(1):462-3
15635016
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W52-7
17537822
Nat Rev Microbiol. 2008 Mar;6(3):181-6
18157154
J Clin Microbiol. 2005 May;43(5):2224-30
15872246
J Biotechnol. 2008 Aug 31;136(1-2):22-30
18430482
Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13950-5
16172379
Plasmid. 2002 Sep;48(2):77-97
12383726
Genomics. 1988 Apr;2(3):231-9
3294162
Antimicrob Agents Chemother. 2004 Aug;48(8):3028-32
15273117
Infect Immun. 2004 Aug;72(8):4512-20
15271910
Antimicrob Agents Chemother. 2008 Jun;52(6):2256-9
18391028
Int J Food Microbiol. 2008 Mar 31;123(1-2):38-49
18180067
J Antimicrob Chemother. 2001 Jul;48 Suppl 1:5-16
11420333
J Bacteriol. 1996 Apr;178(7):1990-5
8606174
Nat Rev Microbiol. 2009 Apr;7(4):287-96
19287448
Mol Microbiol. 2003 Mar;47(6):1733-47
12622825
Nucleic Acids Res. 2001 Jan 1;29(1):22-8
11125040
Infect Immun. 2009 Nov;77(11):5097-106
19737906
Curr Opin Microbiol. 2008 Oct;11(5):472-7
19086349
Antimicrob Agents Chemother. 2008 Mar;52(3):1167-70
18180351
Infect Immun. 2008 Sep;76(9):4120-8
18591236
Int J Food Microbiol. 2003 Dec 1;88(2-3):269-90
14597000
J Infect Dis. 2000 Sep;182(3):816-23
10950776
Syst Biol. 2003 Oct;52(5):696-704
14530136
Nature. 2005 Sep 15;437(7057):376-80
16056220
J Bacteriol. 2002 Nov;184(22):6351-6
12399505
J Bacteriol. 2008 Nov;190(21):7147-56
18776017
Clin Microbiol Infect. 2007 Mar;13(3):316-9
17391388
Antimicrob Agents Chemother. 1998 Sep;42(9):2463-4
9736587
Nucleic Acids Res. 2000 Jan 1;28(1):263-6
10592242
J Bacteriol. 2004 Feb;186(3):672-82
14729692
Bioinformatics. 2005 Aug 15;21(16):3422-3
15976072
Antimicrob Agents Chemother. 2009 Oct;53(10):4240-6
19667280
Appl Environ Microbiol. 2002 Mar;68(3):1381-91
11872491
Antimicrob Agents Chemother. 1994 Sep;38(9):1980-3
7811006
Bioinformatics. 1998;14(9):755-63
9918945
J Bacteriol. 2000 Jul;182(13):3863-6
10851008
Infect Immun. 2008 Sep;76(9):4110-9
18591238
J Mol Biol. 2001 Jan 19;305(3):567-80
11152613
BMC Bioinformatics. 2004 Aug 19;5:113
15318951
Appl Environ Microbiol. 2003 Oct;69(10):5739-45
14532020
Microb Drug Resist. 2005 Summer;11(2):178-84
15910234
Genome Biol. 2007;8(6):R103
17550610
Nature. 2002 Jun 13;417(6890):746-50
12066186
Genome Biol. 2008;9(7):R110
18611278
J Bacteriol. 2008 Oct;190(20):6913-7
18708498
Clin Microbiol Infect. 2006 Nov;12(11):1123-30
17002613
Annu Rev Microbiol. 2006;60:187-209
16704341
Appl Environ Microbiol. 2006 Sep;72(9):5784-9
16957194
Nucleic Acids Res. 2007;35(9):3100-8
17452365