Transposition of ISAba13 in Acinetobacter baumannii AB5075

Cooper, Charles (2024). Transposition of ISAba13 in Acinetobacter baumannii AB5075. University of Birmingham. Ph.D.

Preview

Cooper2024PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (50MB) | Preview

Abstract

Acinetobacter baumannii is a critical priority category pathogen for which new drug treatments are urgently required. A major cause of nosocomial infection, A. baumannii is able to colonise and persist for long periods of time in hospital environments. Here we have characterised a novel colony variant of the well-studied, highly virulent, and drug-resistant, model strain AB5075.

We determined the biological mechanism for formation of these rare colonies; insertion sequence ISAba13 disrupts gene gtr52 of the capsule synthesis locus. As a consequence, there are profound phenotypic effects. We also probed the effects of ISAba13 on transcription of adjacently located genes. This led to the discovery of the first bidirectional promoter within a bacterial insertion sequence.

Finally, we developed a method termed native Tn-Seq to map genome-wide natural insertions of ISAba13 across a population of AB5075. This highlighted a propensity for insertion into AT-rich DNA, and a pivotal role for the chromosome folding protein H-NS in directing transposition to these regions. We show that the ability of H-NS to bridge DNA is required for directing these transposition events. To our knowledge, this is the first example of a bacterium dictating its own downstream evolution by manipulating patterns of transposition.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):