CIHR-UBC Strategic Training Program for
Translational Research in Infectious Diseases
Address: D452 – 2733 Heather Pavilion, Vancouver, BC V5Z 3J5
E-mail: tonychow@interchange.ubc.ca
Voice: (604) 875-5063 Fax: (604) 875-4013 Website: http://cmdr.ubc.ca/trainingprogram
Research Theme:
Antibiotic resistance, novel therapeutic targets
Sub-theme:
Antibiotic resistance mechanisms and mode-of-action studies on antibiotics
Principal Investigator:
Dr. Julian Davies, PhD, FRS, FRSC
Telephone: (604) 822-5856
Fax:
(604) 822-6041
E-mail:
jed@interchange.ubc.ca
My laboratory will address both of these topics. With respect to antibiotic resistance, we propose to analyse for novel
biochemical mechanisms in newly-isolated strains as they are reported. In addition, we will study the development of
antibiotic resistance – how many genetic changes are required to create robust, resistant strain in a clinical situation?
We will study the interacting roles of mutation, plasmid acquisition and the accompanying compensatory and
antagonistic functions. With techniques that are currently available to detect point mutations in different genes (such as
high resolution base change detection), it should be possible to track resistance development and perhaps identify
compensatory changes as potential new targets for the design of new drugs. As a second topic, we will continue our
studies of antibiotic mode of action and its role in drug discovery. We have found that sub-inhibitory concentrations of
antibiotics modulate (activate or repress) transcription in bacteria. This effect has been identified using promoterreporter fusions and detection of transcription changes by light (lux) or chromogenic (gfp) changes. With the use of
selected promoter fusions and hosts, we plan to develop panels of reporter strains that can be used for mode-of-action
based screening. We also wish to employ reporter panels to identify mechanisms of resistance; such as distinguishing
efflux from target mutation, etc.
Updated: August 2003
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