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Professor Maggie Smith

Emeritus

Overview

Molecular Genetics of the antibiotic-producing bacteria Streptomyces and their bacteriophages. 

 

Bacteria in the genus Streptomyces are prolific producers of antibiotics, anti-cancer agents, immune-suppressants, and other bioactive natural products. The aim of Maggie Smith’s research is to investigate and exploit genetic processes in Streptomyces and their close relatives to facilitate novel drug development.


Colonies of Streptomycelividans growing on an agar plate. The fuzzy surface of the colonies indicate the formation of spores.

colonies of S. lividans

A major theme in Maggie’s lab is to study the genetics of host-phage interactions. A new family of phage-encoded integrases, the serine integrases were first characterised in Maggie’s group. Integrases are natures DNA cut and paste tool and can be used to integrate and excise DNA from chromosomes. This is a useful tool for genetic engineering and has been deployed in bacteria, fungi, animals and plants.  In Streptomyces sp. vectors based on serine integrases are widely used to transfer genes for antibiotic biosynthesis between strains. Maggie’s lab have studied many different serine integrases and are now using them to create stable vectors for the cloning and design of new antibiotics analogues based on erythromycin.


Streptomyces grows with a mycelial growth habit that can be seen under the microscope. 

S. coelicolor hyphae

Left: An electron micrograph of a Streptomyces phage, Joe. Joe was isolated from soil and uses Streptomyces lividans as its host.  

Right: Phage infecting a lawn of Streptomyces growing on an agar plate. Each dark zone or plaque is derived from a single phage particle which kills the bacteria. 

EM of Joe and phage plaques

In other work mutants of Streptomyces were isolated that are resistant to some phages and, surprisingly, hypersensitive to certain antibiotics including two of the last resort antibiotics the carbapenems and vancomycin. These mutants are defective in protein glycosylation. This discovery is being studied further to try to understand the underlying processes that lead to antibiotic hypersensitivity. The goal is to translate this research to pathogenic bacteria to see if we can identify new targets for co-drugs that can be used in conjunction with existing antibiotics to make them more effective.


Strains of Streptomyces coelicolor that are defective in modifying membrane proteins with sugars are hypersensitive to some antibiotics. The plate on the right is sensitive to vancomycin whereas the normal strain on the left is resistant.

Vancomycin sensitivity assay

Publications

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Contact details

Professor Maggie Smith
Department of Biology
University of York
Wentworth Way
YO10 5DD

Tel: +44 1904 328686