Microbial Genomics

This sub-theme applies research in fundamental genetic mechanisms and technologies (many developed by the Genome Science theme), to the study of bacterial genomes and their role in physiology and pathogenesis.

A major interest is in the mechanisms responsible for high frequency generation of genetic variation in microbial genomes, which is key to the remarkable ability of bacteria to adapt to changing selective pressures (for example exposure to
antibiotics and hostile immune responses).

A key achievement in this area is the use of whole-genome sequencing to identify the targets of antibiotic-driven positive selection in multi-drug resistant Mycobacterium tuberculosis (Oggioni).

A particular focus is on the role of hyper-mutable repetitive DNA sequences, which are a prominent feature of microbial genomes and are responsible for localised increases in rates of mutation and recombination resulting in rapid generation of genetic and Phenotypic variation. For example, “mutations” in simple sequence repeats (SSRs), due to spontaneous variation in the number of repeat units, can cause alteration in expression of neighbouring genes (either “on” or “off”) resulting in high frequency, reversible changes, termed phase variation. Many of these genes are involved in the formation of surface structures that interact with host receptors or the immune response which are critical for bacterial survival and/ or Pathogenicity.

The mechanisms and role of phase variation in host colonisation and avoidance of immune responses are being investigated in Campylobacter and Neisseria meningitidis (the causative organism for bacterial meningitis), whose
genomes contain more than 20 genes subject to phase variation mediated by SSRs. Related work is studying the role of a different source of genetic variation, based on horizontal transfer of DNA between bacteria. Another application of genetics to microbial sciences is to exploit the power of high-throughput “next-generation” DNA sequencing technology to “profile” bacterial populations present in a host (the “microbiome”), far more comprehensively and rapidly than could previously be achieved by conventional methods based on culturing live organisms. For example, this approach is being used to characterise changes in the microbiome in patients suffering from antibiotic-associated Clostridium difficile mediated diarrhoea (in particular in cases of relapse). It is also being used to investigate how host responses such as inflammation and stress affect the Microbiome and what are the consequences on pathogen colonisation and virulence – both in man and domestic animals – E.G. the effect of stress on gut Microbiota in chickens.

The key players in this area are Bayliss , Clokie, Oggioni, Ketley and Rajakumar with many others sustaining minor interests.

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Contact Details

College of Life Sciences
University of Leicester
Maurice Shock Building
University Road
Leicester
LE1 7RH