Exit Seminar - Investigating interplay between the pathogen and the host in pathogenic Escherichia coli infection using multi-omics approaches

Sponsored by: UBC Department of Microbiology & Immunology

Abstract: Enteropathogenic Escherichia coli (EPEC) is a bacterial pathogen that causes significant morbidity and mortality worldwide. During infection, EPEC attaches to the intestinal epithelium and utilizes a Type 3 Secretion system (T3SS) to secrete virulence ‘effector’ proteins directly into human cells, where they manipulate host cell physiology to establish a favorable replicative niche. Such complex undertaking requires a significant rewiring of both the host and the pathogen transcriptomes. The host targets of many effectors remain unknown and their collective impact on global host transcriptome has not been widely explored. Using RNA-sequencing approaches, I found that the T3SS subverts host responses during late infection, leading to alterations to pathways involved in cell death and metabolism. There was a significant change in transcriptional regulation by miRNA, several of which were found to reduce the T3SS-associated cell death.  Notably, EPEC has a plethora of effectors involved in cell death modulation. One such effector, map, was shown to be significantly upregulated over the course of infection. Using proteomic proximity-labelling and complementary molecular biology approaches, I identified several host proteins, through which map causes apoptosis. Intriguingly, EPEC’s Type 2 Secretion System (T2SS) was also strongly upregulated during EPEC infection. The role of this virulence system was determined using an in vivo model of infection and model pathogen, Citrobacter rodentium. T2SS proved important for colonization and lethality of infection. This work demonstrates the power of omics techniques to characterize impacts of EPEC infection on the host and identify dysregulated pathways that can inform novel treatments. 

This is a hybrid seminar which you can attend in person in LSC3 (Life Sciences Institute, UBC Vancouver Campus) or on Zoom. If you are joining on zoom, please use the meeting ID and passcode below: 

Meeting ID: 91037 579420 

Passcode: 579420