The Pneumococcal Serine-Rich Repeat Protein Is an Intra-Species Bacterial Adhesin That Promotes Bacterial Aggregation and in Biofilms

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The Pneumococcal serine-rich repeat protein (PsrP) is a pathogenicity island encoded adhesin that has been positively correlated with the ability of Streptococcus pneumoniae to cause invasive disease. Previous studies have shown that PsrP mediates bacterial attachment to Keratin 10 (K10) on the surface of lung cells through amino acids 273–341 located in the Basic Region (BR) domain. In this study we determined that the BR domain of PsrP also mediates an intra-species interaction that promotes the formation of large bacterial aggregates in the nasopharynx and lungs of infected mice as well as in continuous flow-through models of mature biofilms. Using numerous methods, including complementation of mutants with BR domain deficient constructs, fluorescent microscopy with Cy3-labeled recombinant (r)BR, Far Western blotting of bacterial lysates, co-immunoprecipitation with rBR, and growth of biofilms in the presence of antibodies and competitive peptides, we determined that the BR domain, in particular amino acids 122–166 of PsrP, promoted bacterial aggregation and that antibodies against the BR domain were neutralizing. Using similar methodologies, we also determined that SraP and GspB, the Serine-rich repeat proteins (SRRPs) of Staphylococcus aureus and Streptococcus gordonii, respectively, also promoted bacterial aggregation and that their Non-repeat domains bound to their respective SRRPs. This is the first report to show the presence of biofilm-like structures in the lungs of animals infected with S. pneumoniae and show that SRRPs have dual roles as host and bacterial adhesins. These studies suggest that recombinant Non-repeat domains of SRRPs (i.e. BR for S. pneumoniae) may be useful as vaccine antigens to protect against Gram-positive bacteria that cause infection.

Vyšlo v časopise: The Pneumococcal Serine-Rich Repeat Protein Is an Intra-Species Bacterial Adhesin That Promotes Bacterial Aggregation and in Biofilms. PLoS Pathog 6(8): e32767. doi:10.1371/journal.ppat.1001044
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001044

Souhrn

Zdroje

1. 1999 Pneumococcal vaccines. WHO position paper. Wkly Epidemiol Rec 74 177 183

2. LexauCA

LynfieldR

DanilaR

PilishviliT

FacklamR

2005 Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA 294 2043 2051

3. OverturfG

PowarsD

1980 Infections in sickle cell anemia: pathogenesis and control. Tex Rep Biol Med 40 283 292

4. WongWY

OverturfGD

PowarsDR

1992 Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis, and vaccination. Clin Infect Dis 14 1124 1136

5. RoushSW

MurphyTV

2007 Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA 298 2155 2163

6. O'BrienKL

WolfsonLJ

WattJP

HenkleE

Deloria-KnollM

2009 Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374 893 902

7. MaruyamaT

GabazzaEC

MorserJ

TakagiT

D'Alessandro-GabazzaC

2010 Community-acquired pneumonia and nursing home-acquired pneumonia in the very elderly patients. Respir Med 104 584 592

8. ObertC

SublettJ

KaushalD

HinojosaE

BartonT

2006 Identification of a candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease. Infect Immun 74 4766 4777

9. OrihuelaCJ

2009 Role played by psrP-secY2A2 (accessory region 34) in the invasive disease potential of Streptococcus pneumoniae. J Infect Dis 200 1180 1181; author reply 1181–1182

10. HavaDL

CamilliA

2002 Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol Microbiol 45 1389 1406

11. EmbryA

HinojosaE

OrihuelaCJ

2007 Regions of Diversity 8, 9 and 13 contribute to Streptococcus pneumoniae virulence. BMC Microbiol 7 80

12. RoseL

ShivshankarP

HinojosaE

RodriguezA

SanchezCJ

2008 Antibodies against PsrP, a novel Streptococcus pneumoniae adhesin, block adhesion and protect mice against pneumococcal challenge. J Infect Dis 198 375 383

13. ShivshankarP

SanchezC

RoseLF

OrihuelaCJ

2009 The Streptococcus pneumoniae adhesin PsrP binds to Keratin 10 on lung cells. Mol Microbiol 73 663 679

14. TettelinH

NelsonKE

PaulsenIT

EisenJA

ReadTD

2001 Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293 498 506

15. TakamatsuD

BensingBA

SullamPM

2005 Two additional components of the accessory Sec system mediating export of the Streptococcus gordonii platelet-binding protein GspB. J Bacteriol 187 3878 3883

16. TakamatsuD

BensingBA

SullamPM

2004 Four proteins encoded in the gspB-secY2A2 operon of Streptococcus gordonii mediate the intracellular glycosylation of the platelet-binding protein GspB. J Bacteriol 186 7100 7111

17. BensingBA

GibsonBW

SullamPM

2004 The Streptococcus gordonii platelet binding protein GspB undergoes glycosylation independently of export. J Bacteriol 186 638 645

18. TakamatsuD

BensingBA

SullamPM

2004 Genes in the accessory Sec locus of Streptococcus gordonii have three functionally distinct effects on the expression of the platelet-binding protein GspB. Mol Microbiol 52 189 203

19. HammerschmidtS

WolffS

HockeA

RosseauS

MullerE

2005 Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun 73 4653 4667

20. MoscosoM

GarciaE

LopezR

2009 Pneumococcal biofilms. Int Microbiol 12 77 85

21. Hall-StoodleyL

StoodleyP

2009 Evolving concepts in biofilm infections. Cell Microbiol 11 1034 1043

22. Hall-StoodleyL

HuFZ

GiesekeA

NisticoL

NguyenD

2006 Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA 296 202 211

23. ReidSD

HongW

DewKE

WinnDR

PangB

2009 Streptococcus pneumoniae forms surface-attached communities in the middle ear of experimentally infected chinchillas. J Infect Dis 199 786 794

24. LizcanoA

ChinT

SauerK

TuomanenEI

OrihuelaCJ

2010 Early biofilm formation on microtiter plates is not correlated with the invasive disease potential of Streptococcus pneumoniae. Microb Pathog 48 124 130

25. AllegrucciM

HuFZ

ShenK

HayesJ

EhrlichGD

2006 Phenotypic characterization of Streptococcus pneumoniae biofilm development. J Bacteriol 188 2325 2335

26. TakamatsuD

BensingBA

ChengH

JarvisGA

SibooIR

2005 Binding of the Streptococcus gordonii surface glycoproteins GspB and Hsa to specific carbohydrate structures on platelet membrane glycoprotein Ibalpha. Mol Microbiol 58 380 392

27. SibooIR

ChambersHF

SullamPM

2005 Role of SraP, a Serine-Rich Surface Protein of Staphylococcus aureus, in binding to human platelets. Infect Immun 73 2273 2280

28. XiongYQ

BensingBA

BayerAS

ChambersHF

SullamPM

2008 Role of the serine-rich surface glycoprotein GspB of Streptococcus gordonii in the pathogenesis of infective endocarditis. Microb Pathog 45 297 301

29. SamenU

EikmannsBJ

ReinscheidDJ

BorgesF

2007 The surface protein Srr-1 of Streptococcus agalactiae binds human keratin 4 and promotes adherence to epithelial HEp-2 cells. Infect Immun 75 5405 5414

30. van SorgeNM

QuachD

GurneyMA

SullamPM

NizetV

2009 The Group B Streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood-brain barrier. J Infect Dis 199 1479 1487

31. FroeligerEH

Fives-TaylorP

2001 Streptococcus parasanguis fimbria-associated adhesin Fap1 is required for biofilm formation. Infect Immun 69 2512 2519

32. HandleyPS

CorreiaFF

RussellK

RosanB

DiRienzoJM

2005 Association of a novel high molecular weight, serine-rich protein (SrpA) with fibril-mediated adhesion of the oral biofilm bacterium Streptococcus cristatus. Oral Microbiol Immunol 20 131 140

33. Konto-GhiorghiY

MaireyE

MalletA

DumenilG

CaliotE

2009 Dual role for pilus in adherence to epithelial cells and biofilm formation in Streptococcus agalactiae. PLoS Pathog 5 e1000422

34. ManettiAG

ZingarettiC

FalugiF

CapoS

BombaciM

2007 Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation. Mol Microbiol 64 968 983

35. HelaineS

CarbonnelleE

ProuvensierL

BerettiJL

NassifX

2005 PilX, a pilus-associated protein essential for bacterial aggregation, is a key to pilus-facilitated attachment of Neisseria meningitidis to human cells. Mol Microbiol 55 65 77

36. Munoz-EliasEJ

MarcanoJ

CamilliA

2008 Isolation of Streptococcus pneumoniae biofilm mutants and their characterization during nasopharyngeal colonization. Infect Immun 76 5049 5061

37. ParkerD

SoongG

PlanetP

BrowerJ

RatnerAJ

2009 The NanA neuraminidase of Streptococcus pneumoniae is involved in biofilm formation. Infect Immun 77 3722 3730

38. TrappettiC

KadiogluA

CarterM

HayreJ

IannelliF

2009 Sialic acid: a preventable signal for pneumococcal biofilm formation, colonization, and invasion of the host. J Infect Dis 199 1497 1505

39. SoongG

MuirA

GomezMI

WaksJ

ReddyB

2006 Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production. J Clin Invest 116 2297 2305

40. OggioniMR

TrappettiC

KadiogluA

CassoneM

IannelliF

2006 Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis. Mol Microbiol 61 1196 1210

41. AspirasMB

EllenRP

CvitkovitchDG

2004 ComX activity of Streptococcus mutans growing in biofilms. FEMS Microbiol Lett 238 167 174

42. AllegrucciM

SauerK

2007 Characterization of colony morphology variants isolated from Streptococcus pneumoniae biofilms. J Bacteriol 189 2030 2038

43. MoscosoM

GarciaE

LopezR

2006 Biofilm formation by Streptococcus pneumoniae: Role of choline, extracellular DNA, and capsular polysaccharide in microbial accretion. J Bacteriol 188 7785 7795

44. OrihuelaCJ

RadinJN

SublettJE

GaoG

KaushalD

2004 Microarray analysis of pneumococcal gene expression during invasive disease. Infect Immun 72 5582 5596

45. WuH

ZengM

Fives-TaylorP

2007 The glycan moieties and the N-terminal polypeptide backbone of a fimbria-associated adhesin, Fap1, play distinct roles in the biofilm development of Streptococcus parasanguinis. Infect Immun 75 2181 2188

46. StephensonAE

WuH

NovakJ

TomanaM

MintzK

2002 The Fap1 fimbrial adhesin is a glycoprotein: Antibodies specific for the glycan moiety block the adhesion of Streptococcus parasanguis in an in vitro tooth model. Mol Microbiol 43 147 157

47. ZhouM

WuH

2009 Glycosylation and biogenesis of a family of serine-rich bacterial adhesins. Microbiology 155 317 327

48. MannB

OrihuelaC

AntikainenJ

GaoG

SublettJ

2006 Multifunctional role of Choline binding protein G in pneumococcal pathogenesis. Infect Immun 74 821 829

49. SheldonH

ZetterquistH

1955 Internal ultrastructure in granules of white blood cells of the mouse; a preliminary note. Bull Johns Hopkins Hosp 96 135 139

50. IzanoEA

AmaranteMA

KherWB

KaplanJB

2008 Differential roles of poly-N-acetylglucosamine surface polysaccharide and extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis biofilms. Appl Environ Microbiol 74 470 476

51. LooCY

CorlissDA

GaneshkumarN

2000 Streptococcus gordonii biofilm formation: identification of genes that code for biofilm phenotypes. J Bacteriol 182 1374 1382

52. HeydornA

NielsenAT

HentzerM

SternbergC

GivskovM

2000 Quantification of biofilm structures by the novel computer program COMSTAT. Microbiology 146 (Pt 10) 2395 2407

53. TakamatsuD

BensingBA