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Prevalence of strains of Streptococcus mutans expressing Cnm in children and adults, and the role of this glycoprotein in the pathogen-host interactions

Grant number: 13/25080-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2014
Effective date (End): April 30, 2017
Field of knowledge:Health Sciences - Dentistry - Social and Preventive Dentistry
Principal Investigator:Pedro Luiz Rosalen
Grantee:Irlan de Almeida Freires
Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Associated scholarship(s):14/07231-0 - Prevalence of Cnm-expressing Streptococcus mutans and the role of this glycoprotein on platelet activation and adherence to cardiac tissues, BE.EP.DR


Streptococcus mutans is the leading microorganism associated with dental caries, the most common infectious disease afflicting humans, and it is also considered an important agent in the establishment of infective endocarditis (IE), a serious and negligible infection with high mortality rates. Invasive strains of S. mutans mainly of serotypes f and k were found to express a surface collagen-binding protein named Cnm, which avidly binds to collagen and laminin (extracellular matrix) and is associated with an increased ability of S. mutans to colonize human tissues, particularly coronary artery endothelial cells. These findings strongly suggest that the adhesion, invasion and persistence of S. mutans in the host's cytoplasm is an important pathogenic trait, hitherto unknown, which characterizes the presence of Cnm as a new virulence factor related to this microorganism. Hence, it was accomplished the molecular characterization of the cnm locus (transcriptional organization of the cnm operon, identification of environmental factors controlling the expression of Cnm), as well as the functional analysis of Cnm in relation to the binding to host's extracellular matrix. Ultimately, its biological ability of glycosylation was also assessed (unpublished data). Complementary, and because of the need to elucidate the mechanisms by which S. mutans interacts with the host, we aimed in this project to determine the prevalence of S. mutans strains expressing Cnm from caries-free and caries-active children and adults and establish a correlation between the presence of Cnm-expressing strains and the caries status of the individuals. Moreover, these Cnm-positive strains will be used to further investigate the role of such glycoprotein in the development and severity of root caries lesions in an animal model and in the S. mutans - host interactions (in vitro). Initially, samples of saliva, dental plaque and carious tissue will be collected from different caries-free and caries-active groups (children and smoker/non-smoker adults) and subjected to tests to identify which isolates express Cnm. Then, the Cnm-positive clinical isolates will be used to investigate the influence of such glycoprotein in the development and severity of root caries lesions in rats. Subsequently, the Cnm-positive isolates and also strains of S. mutans UA159 (non-invasive and Cnm-negative) and OMZ175 (invasive and Cnm-positive), cnm mutants and recombinant strains of Lactobacillus lactis expressing cnm will be used in the platelet activation assays, including the isolation of platelets from healthy donors and evaluation of bacterial-platelet complexes and platelet activation by flow cytometry. Subsequently, these microorganisms will be assessed for adhesion to heart valves using an ex vivo porcine model and evaluated by Field Emission Scanning Electron Microscopy. The results of this research project are expected to provide new knowledge on the mechanisms linking Cnm to oral diseases, such as tooth decay, and to extra-oral diseases, such as IE. At the end of this project, we will have determined the prevalence of strains expressing Cnm in different age groups and the influence of such glycoprotein in the development and severity of caries. Ultimately, we will have established the role of Cnm in processes related to the pathogenesis of IE such as platelet activation and adherence to cardiac tissues.

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Scientific publications (9)
(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)
FREIRES, I. A.; QUEIROZ, V. C. P. P.; FURLETTI, V. F.; IKEGAKI, M.; DE ALENCAR, S. M.; DUARTE, M. C. T.; ROSALEN, P. L.. Chemical composition and antifungal potential of Brazilian propolis against Candida spp.. JOURNAL DE MYCOLOGIE MEDICALE, v. 26, n. 2, p. 122-132, . (13/25080-7)
FREIRES, IRLAN ALMEIDA; DENNY, CARINA; BENSO, BRUNA; DE ALENCAR, SEVERINO MATIAS; ROSALEN, PEDRO LUIZ. Antibacterial Activity of Essential Oils and Their Isolated Constituents against Cariogenic Bacteria: A Systematic Review. Molecules, v. 20, n. 4, p. 7329-7358, . (11/15984-0, 11/14757-0, 13/25080-7)
FREIRES, IRIAN ALMEIDA; SANTAELLA, GUSTAVO MACHADO; ORLANDI SARDI, JANAINA DE CASSIA; ROSALEN, PEDRO LUIZ. The alveolar bone protective effects of natural products: A systematic review. ARCHIVES OF ORAL BIOLOGY, v. 87, p. 196-203, . (11/15984-0, 13/25080-7)
FREIRES, IRLAN A.; AVILES-REYES, ALEJANDRO; KITTEN, TODD; SIMPSON-HAIDARIS, P. J.; SWARTZ, MICHAEL; KNIGHT, PETER A.; ROSALEN, PEDRO L.; LEMOS, JOSE A.; ABRANCHES, JACQUELINE. Heterologous expression of Streptococcus mutans Cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence. VIRULENCE, v. 8, n. 1, p. 18-29, . (14/07231-0, 13/25080-7)
PEREIRA, JOZINETE VIEIRA; FREIRES, IRLAN ALMEIDA; CASTILHO, ALINE ROG ERIA; DA CUNHA, MARCOS GUILHERME; ALVES, HARLEY DA SILVA; ROSALEN, PEDRO LUIZ. Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans. Pharmaceutical Biology, v. 54, n. 10, p. 2312-2319, . (13/25080-7, 11/23635-6, 14/01723-9)
FREIRES, IRLAN ALMEIDA; DE ALENCAR, SEVERINO MATIAS; ROSALEN, PEDRO LUIZ. A pharmacological perspective on the use of Brazilian Red Propolis and its isolated compounds against human diseases. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 110, p. 267-279, . (11/15984-0, 13/25080-7)
FREIRES, IRLAN ALMEIDA; ROSALEN, PEDRO LUIZ. How Natural Product Research has Contributed to Oral Care Product Development? A Critical View. PHARMACEUTICAL RESEARCH, v. 33, n. 6, p. 1311-1317, . (11/15984-0, 13/25080-7)
FREIRES, IRLAN ALMEIDA; DE CASSIA ORLANDI SARDI, JANAINA; DE CASTRO, RICARDO DIAS; ROSALEN, PEDRO LUIZ. Alternative Animal and Non-Animal Models for Drug Discovery and Development: Bonus or Burden?. PHARMACEUTICAL RESEARCH, v. 34, n. 4, p. 681-686, . (11/15984-0, 13/25080-7)
AVILES-REYES, ALEJANDRO; FREIRES, IRLAN ALMEIDA; ROSALEN, PEDRO LUIZ; LEMOS, JOSE A.; ABRANCHES, JACQUELINE. Ex vivo Model of Human Aortic Valve Bacterial Colonization. BIO-PROTOCOL, v. 7, n. 11, . (13/25080-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FREIRES, Irlan de Almeida. The role of Streptococcus mutans Cnm in intracellular invasion, adhesion to human cardiac tissues, and cariogenicity in vivo. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.

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