Análise da sinalização química e virulência em Escherichia coli enterohemorrágica e Citrobacter rodentium mediado por membros da microbiota

Author(s)

Karine Melchior

• Document type: Master's Dissertation
• Press: Araraquara. 0000-00-00.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2020-06-25
• Advisor: Cristiano Gallina Moreira

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a gastrointestinal pathogen well known for its ability to cause hemorrhagic diarrhea. It has in its genome the Island of pathogenicity locus of enterocyte effacement (LEE), responsible for encoding genes related to important virulence factors. The QseC histidine kinase sensor, present in the EHEC membrane, regulates this island. Recently, our group demonstrated that commensal bacteria beneficial to the microbiota, such as Bacteroides tethaitaomicron (Bt), can antagonically increase the expression of virulence genes in pathogenic bacteria, such as EHEC, by altering the metabolic landscape. In this way, this work aimed to understand the regulation of EHEC virulence in the presence of butyrate, as well as commensal bacteria, in order to understand the relationship between microbiota - pathogen, how the pathogen modulates its response to the environment, as well as participation of the QseC sensor in the signaling involved in these processes. The results obtained in this study, showed that QseC changes the gene regulation through butyrate in EHEC and there were differences in the motility and growth in presence of this fatty acidThe expression of hcp-2 gene from T6SS is increased in low glucose, nevertheless decreased in the mutant strain, indicating that QseC modulates this system. However, the introduction of Bt in low glucose media, induced a decrease in the expression of the hcp-2 gene in EHEC, which indicates a regulation of this commensal bacterium in the T6SS of this pathogen. Beneficial members of the human microbiota were increased in the absence of QseC in the Human Intestinal Microbial Ecosystem Simulator, indicating differences in EHEC competition in the absence of this sensor. Lactobacillus acidophilus decreased the growth of EHEC, however the same was not observed for Lactobacillus reuteri, indicating the inhibition observed is Lactobacillus strain-dependent. The QseC sensor is necessary for an effective colonization and dissemination of Citrobacter rodentium in C57BL/6 mice. Therefore, these results indicate that members of the microbiota modulate EHEC response, the QseC sensor has a role in signaling promoted by these commensal bacteria and is necessary for effective colonization in the host. (AU)

• FAPESP's process: 18/22042-0 - Chemical signaling and virulence in Escherichia coli enterohemorrhagic mediated by members of the microbiota
• Grantee: Karine Melchior
• Support Opportunities: Scholarships in Brazil - Master