Development of a bacterial adhesin into a next generation antimicrobial agent

Al-Saedi, Fitua Minuar Aziz (2018). Development of a bacterial adhesin into a next generation antimicrobial agent. University of Birmingham. Ph.D.

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Abstract

For most pathogenic bacteria, the adherence to host cells is a crucial step for infection. Therefore, targeting bacterial attachment could be a potential way for treating bacterial infections. This thesis focuses on the interactions between the adhesin Multivalent Adhesion Molecule (MAM7) from the commensal Escherichia coli strain HS with host receptors, aiming to understand the molecular basis of these interactions. Targeting the interactions between MAM7 and host cells was one of this study’s aims towards developing anti-bacterial agents. In this study, HSMAM7 based adhesion inhibitors- beads coupled to HSMAM7 and an engineered bacterium expressing HSMAM7- were designed and their role as anti–adhesion agents against pathogenic bacteria was investigated. This study demonstrates that HSMAM7 based inhibitors have the ability to displace pathogenic bacteria from the host cells.
Dissecting the binding of HSMAM7 to host receptors was the second part of this study. The findings revealed that HSMAM7 binds to sulfatide, several components of the extracellular matrix (ECM) and mucin. Further investigation of the interaction between HSMAM and host receptors revealed that HSMAM7 binds to mucin and the host lipid sulfatides via specific recognition of a shared 3-O-sulfo-galactosyl moiety in a sulfation dependent manner.
Sulfatase-producing Bacteroides thetaiotaomicron affect the binding of HSMAM7 to mucin. HSMAM7 binding to mucin was inhibited in the presence of B. thetaiotaomicron and that means the commensal E. coli would be free and able to attach to the host epithelial cells, a finding of potential relevance for inflammatory bowel diseases (IBDs).

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):