BACTERICIDAL EFFECTS OF CHLOROQUINE ON ESCHERICHIA COLI : The effects of chloroquine on the viability of growing and non-growing Escherichia co1i in a MOPS (3-(N-Morpholino)-propanesulphonic acid) buffered medium, and its effect on thymidine utilisation
BACTERICIDAL EFFECTS OF CHLOROQUINE ON ESCHERICHIA COLI : The effects of chloroquine on the viability of growing and non-growing Escherichia co1i in a MOPS (3-(N-Morpholino)-propanesulphonic acid) buffered medium, and its effect on thymidine utilisation
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Date
1979-05
Authors
Olurinola, Philip Folaranmi
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Abstract
The bactericidal effects of chloroquine on growing and nongrowing
cells of Escherichia coli NCTC 1093 were investigated under
controlled experimental conditions in a MOPS buffered minimal salts
medium. Changes in cell mass and viable cell numbers were determined
by measurements of absorbance at 600nm, and by viable cell
counts respectively.
At pH 7.4, the approximate minimum bactericidal concentration
of chloroquine for the organism was 1.0 x 10-3M. This concentration
caused about 3 log cycles of kill within 2 hours, with an initial short
lag before kill commenced. Variation in the drug concentration up to
a ten-fold increase had no significant effect en the rate of kill, although
the time of maintenance of that rate was increased. In nongrowing
(glucose-starved) cells treated with the same drug concentrations,
however, there was virtually no loss in viability for at least
3 hours, except with the highest drug concentration used. Removal of
glucose from cultures treated with chloroquine did not appear to affect
bactericidal activity. The effect of pH on the action of chloroquine was also examined.
A four-fold increase in activity was observed with increase in pH from
6.7 to 7.7, and calculations indicated that both the monoprotonated
and diprotonated forms of chloroquine were biologically active, but
that the diprotonated form was only l/25th as effective as the monoprotonated Cellular uptake studies of chloroquine by a direct method, using
C-labelled chloroquine suggested a biphasic uptake process, a rapid
initial passive uptake followed by a slower active one. The latter
apparently did not occur in the absence of glucose.
The effect of the drug on the utilisation of thymidine by E. coli
cells was investigated. Chloroquine rapidly and strongly inhibited
both the uptake and incorporation of
14C-thymidine into the cells,
and caused a breakdown of preformed DNA.
This work establishes the bactericidal action of chloroquine
against growing cells of E. coli, and indicates that its antibacterial
activity has some similarity to the phenomenon of thymineless death
Description
A Dissertation submitted by
Philip Folaranmi Olurinola, B.Sc.(Pharm.), Ph.C., M.P.S.N.
to the University of Bradford
for the degree of Doctor of Philosophy
Postgraduate School of Studies in Pharmacy,
University of Bradford
May, 1979
Keywords
BACTERICIDAL,, CHLOROQUINE,, ESCHERICHIA COLI