Glucosyltransferases of viridans streptococci are modulins of interleukin-6 induction in infective endocarditis.
The glucosyltransferases (GTFs) of viridans streptococci, common pathogens of infective endocarditis, are extracellular proteins that convert sucrose into exopolysaccharides and glucans. GTFs B, C, and D of Streptococcus mutans are modulins that induce, in vitro and in vivo, the production of cytokines, in particular interleukin-6 (IL-6), from monocytes. The roles of S. mutans GTFs in infectivity and inflammation in situ were tested in a rat experimental model of endocarditis. No significant differences in infectivity, in terms of 95% infective dose and densities of bacteria inside vegetations, were observed between laboratory strain GS-5 and two clinical isolates or isogenic mutant NHS1DD, defective in the expression of GTFs. In aortic valves and surrounding tissues, IL-6 was detected by Western blots and immunostaining 24 h after GS-5 infection, was maintained over 72 h, and was followed by production of tumor necrosis factor alpha but not IL-1beta. Animals infected with NHS1DD showed markedly lower levels of IL-6 (less than 5% of that of parental GS-5-infected rats), while tumor necrosis factor alpha was unaffected. In contrast, animals infected with NHR1DD, another isogenic mutant expressing only GtfB, showed a much smaller reduction (down to 56%). These results suggest that GTFs are specific modulins that act during acute inflammation, inducing IL-6 from endothelial cells surrounding the infected valves without affecting bacterial colonization in vegetations, and that IL-6 might persist in chronic inflammation in endocarditis.
Shun
Chia-Tung
CT
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, No. 1 Jen Ai Road, 1st Section, Room 713, Taipei, Taiwan.
Lu
Shih-Yu
SY
Yeh
Chiou-Yueh
CY
Chiang
Chung-Pin
CP
Chia
Jean-San
JS
Chen
Jen-Yang
JY
D000818:Animals; D004697:Endocarditis, Bacterial / Q000276:immunology* / Q000473:pathology; D005260:Female; D005964:Glucosyltransferases / Q000502:physiology*; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D013290:Streptococcal Infections / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D034363:Viridans Streptococci / Q000201:enzymology* / Q000472:pathogenicity; D014774:Virulence
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005964:Glucosyltransferases