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Associate Professor
Departamento de Análises Clínicas
Faculdade de Ciências Farmacêuticas -UNESP
Rua Expedicionários do Brasil, 1621
CEP: 14801-902
Telephone: +55 16-3301-6556
Fax: +55 16 3301-6547

        Our group is engaged in researching the relationship between the fungal pathogen and
its host. In this endeavor, we have developed a cell-culture model designed to unravel the steps
involved in the process of infection, from the first contact of the fungus to the adhesion and
invasion events that culminate in its establishment inside the mammalian cell. Currently, we are
studying the adhesins produced and the signaling events that occur during contact between cells
of   Paracoccidioides   brasiliensis   and   epithelial   and   mononuclear     cells,   employing
immunocytochemical, molecular and proteomic methods. By these methods, not only have we
demonstrated that P. brasiliensis has the capacity to invade human and animal epithelial cell
lines, but have also shown a correlation, for the first time, between the degree of virulence and
adhesion capacity of different strains of the fungus. Further, we proved that their pattern of
adhesion to individual components of the extracellular matrix, such as types I and IV collagen,
laminin, fibronectin and entactin, differed between samples showing different degrees of
virulence. Recently, a 30 kDa adhesin was isolated from P. brasiliensis that showed an ability to
bind laminin. This protein was expressed more strongly in an isolate of the fungus that
possessed a high capacity for adhesion. In experiments to elucidate the role of 30 and 43 kDa
fungal proteins in interactions with epithelial cells, the adhesion of P. brasiliensis was found to
be greatly inhibited when the epithelial cells were pretreated with these adhesins. Among the
components of the host cytoskeleton, we have shown that this fungus probably makes use of
actin and tubulin to gain entrance to the cell and that cytokeratin also seems to play an
important part. Finally, in the same mammalian cell cultures, it was observed that P. brasiliensis
and some of its components were capable of inducing apoptosis in epithelial cells.
        Another line of research in this laboratory concerns the molecular epidemiology of the
major fungi affecting immunocompetent and immunodeficient patients, with the aim of finding
out which are the main classes of molecules involved in human fungal disease and recording the
sensitivity profiles of these organisms to the main antifungal agents used in clinical treatment.
We have an ongoing interest in the study of isolates that show resistance to antifungal drugs, in
particular the azoles, in the hope of discovering new mechanisms of resistance.
        In very recent work we have applied representational difference analysis to identifying
the genes likely to be involved in the fungal infection process. We also contribute to the FAPESP
BIOTA project and its database, BIOprospecTA, screening plant species of the cerrado
(savannah-like scrub forest) and Atlantic Forest biomes for antifungal substances.
Barbosa MS, Bao SN, Andreotti PF, de Faria FP, Felipe MS, dos Santos Feitosa L, Mendes-
Giannini MJ, Soares CM.
Glyceraldehyde-3-phosphate dehydrogenase of Paracoccidioides brasiliensis is a cell surface
protein involved in fungal adhesion to extracellular matrix proteins and interaction with cells.
Infect Immun. 2006 Jan;74(1):382-9.
Mendes-Giannini MJ, Soares CP, da Silva JL, Andreotti PF.
Interaction of pathogenic fungi with host cells: Molecular and cellular approaches.
FEMS Immunol Med Microbiol. 2005 Sep 1;45(3):383-94. Review.
Andreotti PF, Monteiro da Silva JL, Bailao AM, Soares CM, Benard G, Soares CP, Mendes-
Giannini MJ.
Isolation and partial characterization of a 30 kDa adhesin from Paracoccidioides brasiliensis.
Microbes Infect. 2005 May;7(5-6):875-81.
Mendes-Giannini MJ, Hanna SA, da Silva JL, Andreotti PF, Vincenzi LR, Benard G, Lenzi HL,
Soares CP.
Invasion of epithelial mammalian cells by Paracoccidioides brasiliensis leads to cytoskeletal
rearrangement and apoptosis of the host cell.
Microbes Infect. 2004 Aug;6(10):882-91
Benard G, Kavakama J, Mendes-Giannini MJ, Kono A, Duarte AJ, Shikanai-Yasuda MA.
Contribution to the natural history of paracoccidioidomycosis: identification of the primary
pulmonary infection in the severe acute form of the disease--a case report.
Clin Infect Dis. 2005 Jan 1;40(1):e1-4.
Romano CC, Mendes-Giannini MJ, Duarte AJ, Benard G.
The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta2
receptor on patients with active or treated paracoccidioidomycosis and healthy infected
subjects.Clin Immunol. 2005 Jan;114(1):86-94.
Martins-Diniz JN, da Silva RA, Miranda ET, Mendes-Giannini MJ.
Monitoring of airborne fungus and yeast species in a hospital unit]
Rev Saude Publica. 2005 Jun;39(3):398-405.
Baeza, LC; Giannini,MJ
Strain differentiation of Trichophyton rubrum by random amplification of polymorphic DNA
(RAPD). Rev Inst Med Trop Sao Paulo. 2004 Nov-Dec;46(6):339-41.
Raso TF, Werther K, Miranda ET, Mendes-Giannini MJ.
Cryptococcosis outbreak in psittacine birds in Brazil. Med Mycol. 2004 Aug;42(4):355-62.
Romano CC, Mendes-Giannini MJ, Duarte AJ, Benard G.
IL-12 and neutralization of endogenous IL-10 revert the in vitro antigen-specific cellular
immunosuppression of paracoccidioidomycosis patients. Cytokine. 2002 May 7;18(3):149-57.
Cacere CR, Romano CC, Mendes Giannini MJ, Duarte AJ, Benard G.
The role of apoptosis in the antigen-specific T cell hyporesponsiveness of paracoccidioidomycosis
patients.Clin Immunol. 2002 Nov;105(2):215-22.
Biselli PJ, Juvenale M, Mendes-Giannini MJ, Duarte AJ, Benardi G.
IgE antibody response to the main antigenic component of Paracoccidioides brasiliensis in
patients with paracoccidioidomycosis.Med Mycol. 2001 Dec;39(6):475-8.
Benard G, Romano CC, Cacere CR, Juvenale M, Mendes-Giannini MJ, Duarte AJ.
Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with
human paracoccidioidomycosis. Cytokine. 2001 Feb 21;13(4):248-52.
Verweij PE, Figueroa J, Van Burik J, Holdom MD, Dei-Cas E, Gomez BL, Mendes-Giannini MJ.
Clinical applications of non-culture based methods for the diagnosis and management of
opportunistic and endemic mycoses.Med Mycol. 2000;38 Suppl 1:161-71. Review.
Mendes-Giannini MJ, Taylor ML, Bouchara JB, Burger E, Calich VL, Escalante ED, Hanna SA,
Lenzi HL, Machado MP, Miyaji M, Monteiro Da Silva JL, Mota EM, Restrepo A, Restrepo S,
Tronchin G, Vincenzi LR, Xidieh CF, Zenteno E.
Pathogenesis II: fungal responses to host responses: interaction of host cells with fungi.
Med Mycol. 2000;38 Suppl 1:113-23. Review
Hanna SA, Monteiro da Silva JL, Giannini MJ.
Adherence and intracellular parasitism of Paracoccidioides brasiliensis in Vero cells.
Microbes Infect. 2000 Jul;2(8):877-84.

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