Study of the role of the typical enteroaggregative Escherichia coli (EAEC) pAA plasmid in the development of extraintestinal E. coli infections

• Grant number: 22/08145-7
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Tânia Aparecida Tardelli Gomes do Amaral
• Grantee: Tânia Aparecida Tardelli Gomes do Amaral
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ana Carolina de Mello Santos Gheller ; Ulrich Dobrindt
• Associated scholarship(s): 23/05910-7 - Genetic and bioinformatic approaches for comparative and functional analysis of the genome and plasmid of typical EAEC strains isolated from urinary tract infections., BP.TT

Abstract

Classically, pathogenic strains of Escherichia coli were thought to cause intestinal infections (II) or extraintestinal infections (IEI). However, several recent reports have demonstrated the occurrence of E. coli strains causing II and IEI in the same patient. Typical enteroaggregative E. coli (EAEC), one of the intestinal pathogenic E. coli pathotypes, is characterized by harboring a virulence plasmid called pAA, which is directly related to the onset of intestinal infection. On the other hand, a high frequency of EAEC in extraintestinal infections has been reported. The continuous isolation of EAEC strains from these sites, most devoid of virulence factors (VFs) associated with these infections, raised the hypothesis that pAA could encode VFs involved in extraintestinal bacterial virulence. In addition, high global risk E. coli clones that received pAA have been described in children and adults with diarrhea and bloodstream infection, increasing the death rates associated with the disease. It is unknown how much VFs encoded in different pAAs could contribute to the increased capacity of EAEC strains to become potential extraintestinal pathogens. In this project, we will investigate whether the acquisition of pAA would increase the extraintestinal virulence potential of E. coli strains, and its loss by EAEC strains isolated from UTI would attenuate this potential. Therefore, pAA plasmids from EAEC isolated from UTI in Brazil will be transferred to non-pathogenic strains and prototype strains of ExPEC lacking pAA. In addition, pAA from strains of EAEC will be eliminated. The extraintestinal virulence of the resulting strains will be evaluated in vitro and in vivo. In addition, a comparative analysis of the differentially expressed bacterial transcripts obtained in in vivo assays will be conducted, and the changes in the innate immune response resulting from the presence of pAA in the infection model will be evaluated. (AU)