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Dynamic Gene Network Analysis of Caco-2 Cell Response to Shiga Toxin-Producing Escherichia coli-Associated Hemolytic-Uremic Syndrome

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Autor(es):
Bando, Silvia Y. [1] ; Iamashita, Priscila [1] ; Silva, Filipi N. [2] ; Costa, Luciano da F. [2] ; Abe, Cecilia M. [3] ; Bertonha, Fernanda B. [1] ; Guth, Beatriz E. C. [4] ; Fujita, Andre [5] ; Moreira-Filho, Carlos A. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Pediat, Fac Med, BR-05403000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil
[3] Butantan Inst, Lab Bacteriol, BR-05503900 Sao Paulo, SP - Brazil
[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, BR-04023062 Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Inst Matemat & Estat, Dept Comp Sci, BR-05508090 Sao Paulo, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: MICROORGANISMS; v. 7, n. 7 JUL 2019.
Citações Web of Science: 0
Resumo

Shiga toxin-producing Escherichia coli (STEC) O113:H21 strains are associated with human diarrhea and some strains may cause hemolytic-uremic syndrome (HUS). In Brazil, these strains are commonly found in cattle but, so far, were not isolated from HUS patients. Here, a system biology approach was used to investigate the differential transcriptomic and phenotypic responses of enterocyte-like Caco-2 cells to two STEC O113:H21 strains with similar virulence factor profiles (i.e., expressing stx2, ehxA, epeA, espA, iha, saa, sab, and subA): EH41 (Caco-2/EH41), isolated from a HUS patient in Australia, and Ec472/01 (Caco-2/Ec472), isolated from bovine feces in Brazil, during a 3 h period of bacteria-enterocyte interaction. Gene co-expression network analysis for Caco-2/EH41 revealed a quite abrupt pattern of topological variation along 3 h of enterocyte-bacteria interaction when compared with networks obtained for Caco-2/Ec472. Transcriptional module characterization revealed that EH41 induces inflammatory and apoptotic responses in Caco-2 cells just after the first hour of enterocyte-bacteria interaction, whereas the response to Ec472/01 is associated with cytoskeleton organization at the first hour, followed by the expression of immune response modulators. Scanning electron microscopy showed more intense microvilli destruction in Caco-2 cells exposed to EH41 when compared to those exposed to Ec472/01. Altogether, these results show that EH41 expresses virulence genes, inducing a distinctive host cell response, and is likely associated with severe pathogenicity. (AU)

Processo FAPESP: 15/22308-2 - Representações intermediárias em Ciência Computacional para descoberta de conhecimento
Beneficiário:Roberto Marcondes Cesar Junior
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
Beneficiário:Roberto Marcondes Cesar Junior
Linha de fomento: Auxílio à Pesquisa - Temático