Exploring the pathogenic metamorphosis of Escherichia coli of serotype O3:H2 associated with human infections

• Grant number: 22/08132-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2023
• Effective date (End): April 30, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Rodrigo Tavanelli Hernandes
• Grantee: Daiany Ribeiro Paz de Lira
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 17/14821-7 - Exploring novel virulence strategies in Escherichia coli, AP.TEM

Abstract

Pathogenic Escherichia coli is subdivided according to the type of disease that they cause into diarrheagenic E. coli (DEC), associated with intestinal infections, and extra-intestinal E. coli (ExPEC), which causes several infections, among which we can highlight: urinary tract infections (UTI), sepsis and meningitis. Among the DEC pathotypes, enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC) are among the most frequently DEC pathotypes isolated from cases of gastrointestinal infections in Brazil. The main genetic marker of EPEC is the chromosomal pathogenicity island locus of enterocyte effacement (LEE region) and the bfp (bundle-forming pilus) operon, used to subdivide EPEC isolates into typical (bfp+) and atypical (bfp-). EAEC harbors the aggregative adhesion plasmid (pAA), where several virulence factor-encoding genes are located, such as genes encoding proteins necessary for the biogenesis of the aggregative adherence fimbriae (AFF/I-AAF/IV). Recently, our laboratory reported an outbreak of diarrhea in Brazil due to a hybrid aEPEC/EAEC isolate of serotype O3:H2. Looking more closely at the O3:H2 serotype, a recent study showed that the EAEC 17-2 prototype harbors genetic markers common associates with ExPEC isolates and was able to cause UTI in an in vivo experimental model. In view of these observations, we divided the objectives of this study into two central perspectives: (1) to compare the genetic similarity between the isolates involved in the diarrhea outbreak, aEPEC, EAEC and the hybrid aEPEC/EAEC, belonging to the O3:H2 serotype, and (2) to analyze the genetic similarity of E. coli isolates of serotype O3:H2 circulating in Brazil, obtained from intestinal infections (symptomatic or asymptomatic) and UTI, with the isolates involved in the diarrhea outbreak mentioned above. In addition, we are going to evaluate the influence of the AAF/I of the hybrid aEPEC/EAEC on EAEC-associated phenotypes. After classification of these isolates into different E. coli pathogenic groups, representative isolates of each pathogenic group will be sequenced and evaluated in silico, focusing on the genetic similarity of the LEE region between aEPEC and hybrid aEPEC/EAEC, as well as the AAF/I-encoding genes and its regulator among EAEC and hybrid aEPEC/EAEC. All sequenced isolates will be submitted to classificatory and phylogenetic analysis, as well as the pan and core genome will be defined. Together, all these analyses will allow us to better understand the genomic plasticity of E. coli isolates of serotype O3:H2, as well as the influence of these distinct genetic profiles on their pathogenicity.