Ecto-5′-nucleotidase

A candidate virulence factor in Streptococcus sanguinis experimental endocarditis

Jingyuan Fan, Yongshu Zhang, Olivia N. Chuang-Smith, Kristi L Frank, Brian D. Guenther, Marissa Kern, Patrick M. Schlievert, Mark C Herzberg

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Streptococcus sanguinis is the most common cause of infective endocarditis (IE). Since the molecular basis of virulence of this oral commensal bacterium remains unclear, we searched the genome of S. sanguinis for previously unidentified virulence factors. We identified a cell surface ecto-5′-nucleotidase (Nt5e), as a candidate virulence factor. By colorimetric phosphate assay, we showed that S. sanguinis Nt5e can hydrolyze extracellular adenosine triphosphate to generate adenosine. Moreover, a nt5e deletion mutant showed significantly shorter lag time (P<0.05) to onset of platelet aggregation than the wild-type strain, without affecting platelet-bacterial adhesion in vitro (P = 0.98). In the absence of nt5e, S. sanguinis caused IE (4 d) in a rabbit model with significantly decreased mass of vegetations (P<0.01) and recovered bacterial loads (log 10CFU, P = 0.01), suggesting that Nt5e contributes to the virulence of S. sanguinis in vivo. As a virulence factor, Nt5e may function by (i) hydrolyzing ATP, a pro-inflammatory molecule, and generating adenosine, an immunosuppressive molecule to inhibit phagocytic monocytes/macrophages associated with valvular vegetations. (ii) Nt5e-mediated inhibition of platelet aggregation could also delay presentation of platelet microbicidal proteins to infecting bacteria on heart valves. Both plausible Nt5e-dependent mechanisms would promote survival of infecting S. sanguinis. In conclusion, we now show for the first time that streptococcal Nt5e modulates S. sanguinis-induced platelet aggregation and may contribute to the virulence of streptococci in experimental IE.

Original languageEnglish (US)
Article numbere38059
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 7 2012

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Streptococcus sanguinis
5'-nucleotidase
endocarditis
5'-Nucleotidase
Virulence Factors
Platelets
Endocarditis
Streptococcus
Platelet Aggregation
Virulence
virulence
Adenosine
Blood Platelets
Adenosine Triphosphate
platelet aggregation
Agglomeration
Bacterial Adhesion
Bacteria
Bacterial Load
Heart Valves

Cite this

Ecto-5′-nucleotidase : A candidate virulence factor in Streptococcus sanguinis experimental endocarditis. / Fan, Jingyuan; Zhang, Yongshu; Chuang-Smith, Olivia N.; Frank, Kristi L; Guenther, Brian D.; Kern, Marissa; Schlievert, Patrick M.; Herzberg, Mark C.

In: PLoS One, Vol. 7, No. 6, e38059, 07.06.2012.

Research output: Contribution to journalArticle

Fan, J, Zhang, Y, Chuang-Smith, ON, Frank, KL, Guenther, BD, Kern, M, Schlievert, PM & Herzberg, MC 2012, 'Ecto-5′-nucleotidase: A candidate virulence factor in Streptococcus sanguinis experimental endocarditis', PLoS One, vol. 7, no. 6, e38059. https://doi.org/10.1371/journal.pone.0038059
Fan, Jingyuan ; Zhang, Yongshu ; Chuang-Smith, Olivia N. ; Frank, Kristi L ; Guenther, Brian D. ; Kern, Marissa ; Schlievert, Patrick M. ; Herzberg, Mark C. / Ecto-5′-nucleotidase : A candidate virulence factor in Streptococcus sanguinis experimental endocarditis. In: PLoS One. 2012 ; Vol. 7, No. 6.
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