Using genomics to understand bacterial pathways in Enterobacteriaceae

Dunne, Karl (2019). Using genomics to understand bacterial pathways in Enterobacteriaceae. University of Birmingham. Ph.D.

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Abstract

Antibiotic resistant Enterobacteriaceae have been come a dangerous threat as some strains are now almost resistant to all known antibiotics. The two largest causes of antibiotic resistant infections in Enterobacteriaceae are E. coli and K. pneumonia. In 1885, Theodor Escherich first described Escherichia coli. In this study, we report the complete genome sequence of this original E. coli strain. We show it encodes the genes for 4805 proteins, and includes an antimicrobial-resistance locus despite being isolated in the pre-antibiotic era. Armed with the knowledge that antimicrobial loci predate introduction of antibiotics and the rise of Klebsiella antibiotic resistant strains, we turned our focus to K. pneumonia. As most antibiotics target essential proteins encoded by essential genes, we set out to identify them. Using TraDIS we uncover 235 essential genes in K. pneumonia ECL8. Many compounds target key bacterial pathways, but as bacterial have functionally redundant systems these compounds are not lethal. As the need for new antibiotics grows it may be time to use a combination of compounds that target functionally redundant systems. To do this we chose the three main periplasmic chaperones, where we show that despite having overlapping roles they respond to stress in different ways.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):