Importance of the Collagen Adhesin Ace in Pathogenesis and Protection against Experimental Endocarditis
Ace is an adhesin to collagen from Enterococcus faecalis expressed conditionally after growth in serum or in the presence of collagen. Here, we generated an ace deletion mutant and showed that it was significantly attenuated versus wild-type OG1RF in a mixed infection rat endocarditis model (P<0.0001), while no differences were observed in a peritonitis model. Complemented OG1RFΔace (pAT392::ace) enhanced early (4 h) heart valve colonization versus OG1RFΔace (pAT392) (P = 0.0418), suggesting that Ace expression is important for early attachment. By flow cytometry using specific anti-recombinant Ace (rAce) immunoglobulins (Igs), we showed in vivo expression of Ace by OG1RF cells obtained directly from infected vegetations, consistent with our previous finding of anti-Ace antibodies in E. faecalis endocarditis patient sera. Finally, rats actively immunized against rAce were less susceptible to infection by OG1RF than non-immunized (P = 0.0004) or sham-immunized (P = 0.0475) by CFU counts. Similarly, animals given specific anti-rAce Igs were less likely to develop E. faecalis endocarditis (P = 0.0001) and showed fewer CFU in vegetations (P = 0.0146). In conclusion, we have shown for the first time that Ace is involved in pathogenesis of, and is useful for protection against, E. faecalis experimental endocarditis.
Vyšlo v časopise:
Importance of the Collagen Adhesin Ace in Pathogenesis and Protection against Experimental Endocarditis. PLoS Pathog 6(1): e32767. doi:10.1371/journal.ppat.1000716
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000716
Souhrn
Ace is an adhesin to collagen from Enterococcus faecalis expressed conditionally after growth in serum or in the presence of collagen. Here, we generated an ace deletion mutant and showed that it was significantly attenuated versus wild-type OG1RF in a mixed infection rat endocarditis model (P<0.0001), while no differences were observed in a peritonitis model. Complemented OG1RFΔace (pAT392::ace) enhanced early (4 h) heart valve colonization versus OG1RFΔace (pAT392) (P = 0.0418), suggesting that Ace expression is important for early attachment. By flow cytometry using specific anti-recombinant Ace (rAce) immunoglobulins (Igs), we showed in vivo expression of Ace by OG1RF cells obtained directly from infected vegetations, consistent with our previous finding of anti-Ace antibodies in E. faecalis endocarditis patient sera. Finally, rats actively immunized against rAce were less susceptible to infection by OG1RF than non-immunized (P = 0.0004) or sham-immunized (P = 0.0475) by CFU counts. Similarly, animals given specific anti-rAce Igs were less likely to develop E. faecalis endocarditis (P = 0.0001) and showed fewer CFU in vegetations (P = 0.0146). In conclusion, we have shown for the first time that Ace is involved in pathogenesis of, and is useful for protection against, E. faecalis experimental endocarditis.
Zdroje
1. MurrayBE
1990 The life and times of the Enterococcus. Clin Microbiol Rev 3 46 65
2. FowlerVGJr
MiroJM
HoenB
CabellCH
AbrutynE
2005 Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 293 3012 3021
3. MurrayBE
1998 Enterococci.
GorbachSL
BartlettJG
BlacklowNR
Infectious Diseases. Second ed Philadelphia, PA W. B. Saunders Company 1723 1730
4. TleyjehIM
SteckelbergJM
MuradHS
AnavekarNS
GhomrawiHM
2005 Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA 293 3022 3028
5. AriasCA
MurrayBE
2009 Antibiotic-resistant bugs in the 21st century–a clinical super-challenge. N Engl J Med 360 439 443
6. Fernandez-GuerreroML
VerdejoC
AzofraJ
de GorgolasM
1995 Hospital-acquired infectious endocarditis not associated with cardiac surgery: an emerging problem. Clin Infect Dis 20 16 23
7. GiannitsiotiE
SkiadasI
AntoniadouA
TsiodrasS
KanavosK
2007 Nosocomial vs. community-acquired infective endocarditis in Greece: changing epidemiological profile and mortality risk. Clin Microbiol Infect 13 763 769
8. LandrySL
KaiserDL
WenzelRP
1989 Hospital stay and mortality attributed to nosocomial enterococcal bacteremia: a controlled study. Am J Infect Control 17 323 329
9. PattiJM
AllenBL
McGavinMJ
HookM
1994 MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol 48 585 617
10. SillanpaaJ
XuY
NallapareddySR
MurrayBE
HookM
2004 A family of putative MSCRAMMs from Enterococcus faecalis. Microbiology 150 2069 2078
11. NallapareddySR
QinX
WeinstockGM
HookM
MurrayBE
2000 Enterococcus faecalis adhesin, ace, mediates attachment to extracellular matrix proteins collagen type IV and laminin as well as collagen type I. Infect Immun 68 5218 5224
12. RichRL
KreikemeyerB
OwensRT
LaBrenzS
NarayanaSV
1999 Ace is a collagen-binding MSCRAMM from Enterococcus faecalis. J Biol Chem 274 26939 26945
13. TomitaH
IkeY
2004 Tissue-specific adherent Enterococcus faecalis strains that show highly efficient adhesion to human bladder carcinoma T24 cells also adhere to extracellular matrix proteins. Infect Immun 72 5877 5885
14. KowalskiWJ
KasperEL
HattonJF
MurrayBE
NallapareddySR
2006 Enterococcus faecalis adhesin, Ace, mediates attachment to particulate dentin. J Endod 32 634 637
15. LiuQ
PonnurajK
XuY
GaneshVK
SillanpaaJ
2007 The Enterococcus faecalis MSCRAMM Ace binds its ligand by the Collagen Hug model. J Biol Chem 282 19629 19637
16. BowdenMG
HeuckAP
PonnurajK
KolosovaE
ChoeD
2008 Evidence for the “dock, lock, and latch” ligand binding mechanism of the staphylococcal microbial surface component recognizing adhesive matrix molecules (MSCRAMM) SdrG. J Biol Chem 283 638 647
17. PonnurajK
BowdenMG
DavisS
GurusiddappaS
MooreD
2003 A “dock, lock, and latch” structural model for a staphylococcal adhesin binding to fibrinogen. Cell 115 217 228
18. DuhRW
SinghKV
MalathumK
MurrayBE
2001 In vitro activity of 19 antimicrobial agents against enterococci from healthy subjects and hospitalized patients and use of an ace gene probe from Enterococcus faecalis for species identification. Microb Drug Resist 7 39 46
19. NallapareddySR
SinghKV
DuhRW
WeinstockGM
MurrayBE
2000 Diversity of ace, a gene encoding a microbial surface component recognizing adhesive matrix molecules, from different strains of Enterococcus faecalis and evidence for production of ace during human infections. Infect Immun 68 5210 5217
20. NallapareddySR
MurrayBE
2006 Ligand-signaled upregulation of Enterococcus faecalis ace transcription, a mechanism for modulating host-E. faecalis interaction. Infect Immun 74 4982 4989
21. HallAE
GorovitsEL
SyribeysPJ
DomanskiPJ
AmesBR
2007 Monoclonal antibodies recognizing the Enterococcus faecalis collagen-binding MSCRAMM Ace: conditional expression and binding analysis. Microb Pathog 43 55 66
22. EnneVI
DelsolAA
RoeJM
BennettPM
2006 Evidence of antibiotic resistance gene silencing in Escherichia coli. Antimicrob Agents Chemother 50 3003 3010
23. NallapareddySR
SinghKV
MurrayBE
2008 Contribution of the collagen adhesin Acm to pathogenesis of Enterococcus faecium in experimental endocarditis. Infect Immun 76 4120 4128
24. MajcherczykPA
BarblanJL
MoreillonP
EntenzaJM
2008 Development of glycopeptide-intermediate resistance by Staphylococcus aureus leads to attenuated infectivity in a rat model of endocarditis. Microb Pathog 45 408 414
25. AriasCA
MurrayBE
2008 Emergence and management of drug-resistant enterococcal infections. Expert Rev Anti Infect Ther 6 637 655
26. AngristAA
OkaM
1963 Pathogenesis of bacterial endocarditis. JAMA 183 249 252
27. LebretonF
Riboulet-BissonE
SerrorP
SanguinettiM
PosteraroB
2009 ace, which encodes an adhesin in Enterococcus faecalis, is regulated by Ers and is involved in virulence. Infect Immun 77 2832 2839
28. ChowJW
ThalLA
PerriMB
VazquezJA
DonabedianSM
1993 Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis. Antimicrob Agents Chemother 37 2474 2477
29. NallapareddySR
SinghKV
SillanpaaJ
GarsinDA
HookM
2006 Endocarditis and biofilm-associated pili of Enterococcus faecalis. J Clin Invest 116 2799 2807
30. NanniniEC
TengF
SinghKV
MurrayBE
2005 Decreased virulence of a gls24 mutant of Enterococcus faecalis OG1RF in an experimental endocarditis model. Infect Immun 73 7772 7774
31. HienzSA
SchenningsT
HeimdahlA
FlockJI
1996 Collagen binding of Staphylococcus aureus is a virulence factor in experimental endocarditis. J Infect Dis 174 83 88
32. PattiJM
BremellT
Krajewska-PietrasikD
AbdelnourA
TarkowskiA
1994 The Staphylococcus aureus collagen adhesin is a virulence determinant in experimental septic arthritis. Infect Immun 62 152 161
33. LannergardJ
FrykbergL
GussB
2003 Cne, a collagen-binding protein of Streptococcus equi. FEMS Microbiol Lett 222 69 74
34. EsmayPA
BillingtonSJ
LinkMA
SongerJG
JostBH
2003 The Arcanobacterium pyogenes collagen-binding protein, CbpA, promotes adhesion to host cells. Infect Immun 71 4368 4374
35. XuY
LiangX
ChenY
KoehlerTM
HookM
2004 Identification and biochemical characterization of two novel collagen binding MSCRAMMs of Bacillus anthracis. J Biol Chem 279 51760 51768
36. SillanpaaJ
NallapareddySR
QinX
SinghKV
MuznyDM
2009 A collagen-binding adhesin, Acb, and ten other putative MSCRAMM and pilus family proteins of Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis Group, biotype I). J Bacteriol 191 6643 6653
37. ZongY
XuY
LiangX
KeeneDR
HookA
2005 A ‘Collagen Hug’ model for Staphylococcus aureus Cna binding to collagen. EMBO J 24 4224 4236
38. SinghKV
NallapareddySR
MurrayBE
2007 Importance of the ebp (endocarditis- and biofilm-associated pilus) locus in the pathogenesis of Enterococcus faecalis ascending urinary tract infection. J Infect Dis 195 1671 1677
39. CoqueTM
PattersonJE
SteckelbergJM
MurrayBE
1995 Incidence of hemolysin, gelatinase, and aggregation substance among enterococci isolated from patients with endocarditis and other infections and from feces of hospitalized and community-based persons. J Infect Dis 171 1223 1229
40. McCormickJK
HirtH
WatersCM
TrippTJ
DunnyGM
2001 Antibodies to a surface-exposed, N-terminal domain of aggregation substance are not protective in the rabbit model of Enterococcus faecalis infective endocarditis. Infect Immun 69 3305 3314
41. HuebnerJ
QuaasA
KruegerWA
GoldmannDA
PierGB
2000 Prophylactic and therapeutic efficacy of antibodies to a capsular polysaccharide shared among vancomycin-sensitive and -resistant enterococci. Infect Immun 68 4631 4636
42. ChengAG
KimHK
BurtsML
KrauszT
SchneewindO
2009 Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J 23 3393 3404
43. WilsonK
1994 Preparation of genomic DNA from bacteria.
AusubelFM
BrentR
KingstonRE
DavidDM
ScidmanJG
Current Protocols in Molecular Biology Brooklyn, NY Green Publishing Associates 2.4.1 2.4.2
44. WoodfordN
MorrisonD
CooksonB
GeorgeRC
1993 Comparison of high-level gentamicin-resistant Enterococcus faecium isolates from different continents. Antimicrob Agents Chemother 37 681 684
45. SambrookJ
FritschEF
ManiatisT
1989 Molecular cloning: A laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, NY
46. LiX
WeinstockGM
MurrayBE
1995 Generation of auxotrophic mutants of Enterococcus faecalis. J Bacteriol 177 6866 6873
47. SinghKV
MalathumK
MurrayBE
2001 Disruption of an Enterococcus faecium species-specific gene, a homologue of acquired macrolide resistance genes of staphylococci, is associated with an increase in macrolide susceptibility. Antimicrob Agents Chemother 45 263 266
48. SinghKV
CoqueTM
WeinstockGM
MurrayBE
1998 In vivo testing of an Enterococcus faecalis efaA mutant and use of efaA homologs for species identification. FEMS Immunol Med Microbiol 21 323 331
49. MurrayBE
SinghKV
RossRP
HeathJD
DunnyGM
1993 Generation of restriction map of Enterococcus faecalis OG1 and investigation of growth requirements and regions encoding biosynthetic function. J Bacteriol 175 5216 5223
50. NallapareddySR
SinghKV
MurrayBE
2006 Construction of improved temperature-sensitive and mobilizable vectors and their use for constructing mutations in the adhesin-encoding acm gene of poorly transformable clinical Enterococcus faecium strains. Appl Environ Microbiol 72 334 345
51. ArthurM
DepardieuF
SnaithHA
ReynoldsPE
CourvalinP
1994 Contribution of VanY D,D-carboxypeptidase to glycopeptide resistance in Enterococcus faecalis by hydrolysis of peptidoglycan precursors. Antimicrob Agents Chemother 38 1899 1903
52. NallapareddySR
WeinstockGM
MurrayBE
2003 Clinical isolates of Enterococcus faecium exhibit strain-specific collagen binding mediated by Acm, a new member of the MSCRAMM family. Mol Microbiol 47 1733 1747
53. PaceCN
VajdosF
FeeL
GrimsleyG
GrayT
1995 How to measure and predict the molar absorption coefficient of a protein. Protein Sci 4 2411 2423
54. KempKD
SinghKV
NallapareddySR
MurrayBE
2007 Relative contributions of Enterococcus faecalis OG1RF sortase-encoding genes, srtA and bps (srtC), to biofilm formation and a murine model of urinary tract infection. Infect Immun 75 5399 5404
55. ViscountHB
MunroCL
Burnette-CurleyD
PetersonDL
MacrinaFL
1997 Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats. Infect Immun 65 994 1002
56. PeerschkeEI
BayerAS
GhebrehiwetB
XiongYQ
2006 gC1qR/p33 blockade reduces Staphylococcus aureus colonization of target tissues in an animal model of infective endocarditis. Infect Immun 74 4418 4423
57. SinghKV
NallapareddySR
NanniniEC
MurrayBE
2005 Fsr-independent production of protease(s) may explain the lack of attenuation of an Enterococcus faecalis fsr mutant versus a gelE-sprE mutant in induction of endocarditis. Infect Immun 73 4888 4894
58. QueYA
HaefligerJA
PirothL
FrancoisP
WidmerE
2005 Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis. J Exp Med 201 1627 1635
59. ReedLJ
MuenchH
1938 A simple method of estimating fifty percent end points. Am J Hygiene 27 493 497
60. SinghKV
QinX
WeinstockGM
MurrayBE
1998 Generation and testing of mutants of Enterococcus faecalis in a mouse peritonitis model. J Infect Dis 178 1416 1420
61. BourgogneA
GarsinDA
QinX
SinghKV
SillanpaaJ
2008 Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF. Genome Biol 9 R110
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