The role of multidrug efflux pumps in biofilm formation of Salmonella enterica serovar Typhimurium

Baugh, Stephanie (2014). The role of multidrug efflux pumps in biofilm formation of Salmonella enterica serovar Typhimurium. University of Birmingham. Ph.D.

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Multidrug resistance (MDR) efflux pumps and biofilm formation are two mechanisms by which bacteria can evade the action of many antimicrobials. MDR efflux pumps confer low level multidrug resistance and are over-expressed in MDR clinical isolates. Biofilms are three dimensional, complex communities of bacteria encased in a self produced extra cellular matrix. Biofilms protect the bacteria within them both physically by acting as a barrier to any external threats, and metabolically by containing high proportions of persister cells.

This thesis explores the link between MDR efflux and biofilm formation in S. Typhimurium and shows that genetic inactivation of any one of the nine MDR efflux systems results in a biofilm defect. We found that the transcriptional repression of curli, an essential component of the Salmonella matrix, is the reason for the efflux mutants' inability to form a biofilm.

The biofilm defect in a tolC mutant was rescued by inactivation of a gene encoding an osmolarity sensor, envZ, suggesting that membrane stress response is a possible link between efflux and biofilm formation.

Chemical efflux inhibitors (EIs) were found to impart curli repression and cause subsequent biofilm defect. This finding is clinically important as biofilms are a major cause of infection EIs could be a potential novel anti-biofilm therapy.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Immunity and Infection
Funders: None/not applicable
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology


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