Detection and Comparison of Structure and Function of Wild-type Pneumolysin and Its Novel Mutant PlyM2

doi:10.1007/s40242-015-5105-3

Abstract

Abstract:

Here is reported a novel pneumolysin(Ply) mutant(PlyM2) that addresses a long-standing problem for vaccine development in this field: detoxification of Ply in the premise of retaining antigenic integrity. Structure and function of wild-type Ply(PlyWT) and PlyM2 mutants were detected and compared. Their structures were not signi- ficantly different according to the analysis by thermal-dependent fluorescence spectroscopy and circular dichroism spectroscopy. PlyM2 was confirmed to have lost hemolytic activity and yet could induce neutralizing antibodies to prevent in vitro hemolysis by PlyWT and Streptococcus pneumoniae(S. pneumoniae). These results give support to PlyM2 to be a new protein antigen for inclusion in the development of an effective pneumococcal multiprotein vaccine.

Key words: Pneumolysin, Circular dichroism spectroscopy, Thermal-dependent fluorescence spectroscopy, Streptococcus pneumoniae, Detoxification, Mutation

SUN Tianxu, HOU Hongjia, LU Jingcai, XU Man, GU Tiejun, WANG Dandan, DONG Yunliang, JIANG Chunlai, KONG Wei, WU Yongge. Detection and Comparison of Structure and Function of Wild-type Pneumolysin and Its Novel Mutant PlyM2[J]. Chemical Research in Chinese Universities, 2015, 31(4): 553-557.

References

[1] Bogaert D., van Belkum A., Sluijter M., Luijendijk A., de Groot R., Rümke H. C., Verbrugh H. A., Hermans P. W., Lancet, 2004, 363(9424), 1871
[2] Levine O. S., O'Brien K. L., Knoll M., Adegbola R. A., Black S., Cherian T., Dagan R., Goldblatt D., Grange A., Greenwood B., Hennessy T., Klugman K. P., Madhi S. A., Mulholland K., Nohynek H., Santosham M., Saha S. K., Scott J. A., Sow S., Whitney C. G., Cutts F., Lancet, 2006, 367(9526), 1880
[3] van der Poll. T., Opal. S. M., Lancet, 2009, 374(9700), 1543
[4] Reinert R. R., Clin. Microbiol. Infect., 2009, 15(Suppl.3), 7
[5] Weinstein M. P., Klugman K. P., Jones R. N., Clin. Infect. Dis., 2009, 48(11), 1596
[6] Pletz M. W., Maus U., Krug N., Welte T., Lode H., Int. J. Antimicrob. Agents, 2008, 32(3), 199
[7] Weinberger D. M., Dagan R., Givon-Lavi N., Regev-Yochay G., Malley R., Lipsitch M., J. Infect. Dis., 2008, 197(11), 1511
[8] Douglas R. M., Paton J. C., Duncan S. J., Hansman D. J., J. Infect. Dis., 1983, 148(1), 131
[9] Koskela M., Leinonen M., Häivä V. M., Timonen M., Mäkelä P. H., Pediatr. Infect. Dis., 1986, 5(1), 45
[10] Leinonen M., Säkkinen A., Kalliokoski R., Luotonen J., Timonen M., Mäkelä P. H., Pediatr. Infect. Dis., 1986, 5(1), 39
[11] Black S., Shinefield H., Fireman B., Lewis E., Ray P., Hansen J. R., Elvin L., Ensor K. M., Hackell J., Siber G., Malinoski F., Madore D., Chang I., Kohberger R., Watson W., Austrian R., Edwards K., Pediatr. Infect. Dis. J., 2000, 19(3), 187
[12] Black S., Clin. Infect. Dis., 2008, 47(4), 485
[13] Morgan P. J., Hyman S. C., Byron O., Andrew P. W., Mitchell T. J., Rowe A. J., J. Biol. Chem., 1994, 269(41), 25315
[14] Marriott H. M., Mitchell T. J., Dockrell D. H., Curr. Mol. Med., 2008, 8(6), 497
[15] Rubins J. B., Charboneau D., Fasching C., Berry A. M., Paton J. C., Alexander J. E., Andrew P. W., Mitchell T. J., Janoff E. N., Am. J. Respir. Crit. Care Med., 1996, 153, 1339
[16] Jounblat R., Kadioglu A., Mitchell T. J., Andrew P. W., Infect. Immun., 2003, 71(4), 1813
[17] Jefferies J. M., Tocheva A. S., Rubery H., Bennett J., Garland J., Christodoulides M., Faust S. N., Smith A., Mitchell T. J., Clarke S. C., J. Med. Microbiol., 2010, 59, 808
[18] Fu H. Y., Zhu G. L., Wu G. Z., Sha M. L., Dou Q., Chem. Res. Chinese Universities, 2011, 27(4), 688
[19] Wang F., Zhou H. P., Kong B. H., Fan J. H., Chen H. R., Liu J. Y., Chem. Res. Chinese Universities, 2007, 23(5), 562
[20] Shi Q. Y., Zheng Y. C., Ren J. S., Qu X. G., Chem. Res. Chinese Universities, 2008, 24(2), 192
[21] Gao Y., Zhang H., Zhang M., Zhang H., Yu X., Kong W., Zha X., Wu Y., J. Phys. Chem. B, 2010, 114(47), 15656
[22] Yin Q., Zhang Z., Zhao Y. F., Chem. Res. Chinese Universities, 2007, 23(1), 44
[23] Gao Y., Zhang M., Zhang H., Yu X., Kong W., Zha X., Wu Y., J. Phys. Chem. B, 2011, 115(21), 7038