The Role of Highly Phosphorylated Nucleotides in Antibiotic Resistance
of Slow Growing Bacteria.
Supervisors: Dr. Reg England, Dr. Dave Greenway & Professor Eric
Bolton (PHLS- Royal Preston Hospital)
Background: The influence of growth rate and nutrient limitations of
pathogenic bacteria has been extensively studied in chemostat culture
and also within biofilms. It has been unequivocally demonstrated that
a decrease in growth rate of bacteria is accompanied by rapid
alterations in cellular structure and composition associated with
antibiotic resistance mechanisms.
When bacterial cells experience nutrient limitation, their growth rate
decreases and they make a series of rapid adjustments to their
metabolism. One response elicited is the stringent response mediated
by an accumulation of ppGpp, which in turn is the product of relA
gene activity. It is known that in E.coli, ppGpp has a significant
role in growth rate control.
Aims: i) to determine the role of ppGpp in the regulation
of phenotypic antimicrobial resistance mechanisms in E. coli; ii) to
elucidate the interrelationship between ppGpp and sigma factor (*s)
levels as a function of specific growth rate; growth-limiting
substrate; transcript profiles of efflux transport genes; PBP's and
outer membrane porin (OMP) expression; and iii) in collaboration with
PHLS -Royal Preston carry out a wide ranging survey of pathogenic
E.coli strains and to correlate levels of intracellular ppGpp with
antibiotic resistance.
If you have at least an upper second degree in microbiology or
biochemistry and are interested then e-mail either r.england at uclan.ac.uk or
d.greenway at uclan.ac.uk for more details before July 4th.
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Dr Reg England
Department of Applied Biology
University of Central Lancashire
Preston
PR1 2HE
U.K.
Tel: +44 01772 893513
Fax: +44 01772 892929
E-mail: r.england at uclan.ac.uk
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