Regulation of the PatAB efflux pump in streptococcus pneumoniae

Baylay, Alison (2014). Regulation of the PatAB efflux pump in streptococcus pneumoniae. University of Birmingham. Ph.D.

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Abstract

Streptococcus pneumoniae is the primary cause of community acquired pneumonia and represents a substantial disease burden worldwide. The PatAB ABC transporter is a multidrug efflux pump in this organism, encoded by the patA and patB genes, and over-expression of PatAB confers resistance to fluoroquinolone antibiotics.
This thesis investigates the clinical relevance and the regulation of PatAB expression. A strong association was found between cross-resistance to fluoroquinolones and dyes and over-expression of patAB in pneumococcal clinical isolates, supporting previous assertions that PatAB is the main fluoroquinolone efflux pump in S. pneumoniae. Two mechanisms that caused increased expression of patA and patB were identified by whole genome sequencing of multidrug resistant mutants of S. pneumoniae R6. Firstly, a novel duplication of a nine kilobase genomic region, including patA and patB, was identified in one mutant. Further investigation suggested that duplication caused high expression of the second copy of patAB by bringing these genes under the control of a tRNA gene promoter. Secondly, mutations were identified in the terminator stem-loop of a predicted transcriptional attenuator upstream of patA in three other mutants. Transcriptional fusion of mutated attenuator sequences with a GFP reporter gene suggested that these mutations increased transcription from the patA promoter.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):