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Impact of Streptococcus pneumoniae cultivation strategies on capsular polysaccharide production

Grant number: 08/10364-1
Support Opportunities:Regular Research Grants
Duration: June 01, 2009 - May 31, 2011
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Viviane Maimoni Gonçalves
Grantee:Viviane Maimoni Gonçalves
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


S. pneumoniae is a human pathogen which causes 1.9 million deaths of children under 5 years old worldwide each year and the vaccines are not accessible to the poorest people in the world due to their high price. The antigen of the current vaccines is the capsular polysaccharide (PS). In our laboratory, significant results have been obtained for PS production from serotypes 23F and 6B, but biomass and PS productivities are still low, because pneumococcal metabolism is restricted to substrate level phosphorylation and the organic acids produced cause catabolic repression. Therefore, it is essential to develop cultivation strategies and to improve medium formulation with the aim of increasing the PS productivity, making viable the production of a low-cost Brazilian vaccine. This project intends: i) to establish the culture conditions of the three most important pediatric serotypes in Brazil: 1, 6B and 14; ii) to investigate the influence of carbon/nitrogen ratio, bioreactor operation mode and cultivation time on the PS production so that conditions for obtaining high concentration of high molecular mass PS can be identified; iii) to elaborate culture strategies to control the acids formation and to increase the PS production, evaluating the impact of these strategies on the PS characteristics: size and content of proteins and nucleic acids. In order to define the strategies to be adopted, computer simulations will be performed and the experiments will be conducted at different operation modes (repeated batch, fed-batch, fed-batch with medium perfusion) in high performance bioreactors, which are equipped with computational interface for on-line data acquisition and monitoring. The collected data from different cultivations will be used for adjustment of the models, which will be then used to search the Best conditions for obtaining the PS with the desired characteristics. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RODEGE GOGOLA-KOLLING, VERONICA MARIA; ZANARDO, RAFAELA TAIS; CARMO, TALITA SOUZA; ZAMPOLI, NATALIA DALFRE; FIGUEIREDO, DOUGLAS BORGES; GONCALVES, VIVIANE MAIMONI. Improved capsular polysaccharide production by Streptococcus pneumoniae serotype 14 using continuous cultivation. Biochemical Engineering Journal, v. 91, p. 16-22, . (08/05207-4, 08/10364-1)
GONCALVES, VIVIANE M.; DIAS, WALDELY O.; CAMPOS, IVANA B.; LIBERMAN, CELIA; SBROGIO-ALMEIDA, MARIA E.; SILVA, ELIANE P.; CARDOSO, JR., CELSO P.; ALDERSON, MARK; ROBERTSON, GEORGE; MAISONNEUVE, JEAN-FRANCOIS; et al. Development of a whole cell pneumococcal vaccine: BPL inactivation, cGMP production, and stability. Vaccine, v. 32, n. 9, p. 1113-1120, . (08/10364-1)
R. T. ZANARDO; A. L. S. FERRI; D. B. FIGUEIREDO; S. KRASCHOWETZ; J. CABRERA-CRESPO; V. M. GONÇALVES. DEVELOPMENT OF A NEW PROCESS FOR PURIFICATION OF CAPSULAR POLYSACCHARIDE FROM Streptococcus pneumoniae SEROTYPE 14. Brazilian Journal of Chemical Engineering, v. 33, n. 3, p. 435-443, . (08/05207-4, 08/10364-1, 11/02805-0, 12/04858-7)
MARTHOS, BRUNO VITORIO; SILVA FERRI, ANNE LETICIA; DE FIGUEIREDO, DOUGLAS BORGES; ZANGIROLAMI, TERESA CRISTINA; GONCALVES, VIVIANE MAIMONI. Capsular polysaccharide production by Streptococcus pneumoniae serotype 1: from strain selection to fed-batch cultivation. Applied Microbiology and Biotechnology, v. 99, n. 24, p. 10447-10456, . (11/01262-3, 08/05207-4, 11/02805-0, 08/10364-1)

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