Antibacterial action of quinolones on Escherichia coli

Mahmood, Fakhira (1967) Antibacterial action of quinolones on Escherichia coli. PhD thesis, University of Glasgow.

Abstract

Quinolones exhibit both bacteriostatic and bactericidal actions against three strains of Escherichia coli (ATCC 11229/198, NCIB 8114 and 8583). A carboxylic quinolone (N-ethyl-3-carboxyl-7-chloro-4-quinolone, "carboxyQ") is characterised by an absolute requirement for growing cells to exert its antibacterial action. It does not affect susceptible cells during lag phase when the cells are not actively dividing. Its effect on growth and viability is noticed only after the control enters the logarithmic phase of growth and its action diminishes when the control approaches stationary phase. Moreover, its action is completely antagonized under conditions where growth is prevented by withdrawal of an essential nutrient. If the essential nutrient is added to cells pre-incubated in deficient medium with carboxyQ, a period of induction is still required before any antibacterial effect of carboxyQ is observed. Inhibition of growth, e.g. by addition of chloramphenicol, reduces the antibacterial action appreciably. Its activity is also proportional to the rate of growth. A noncarbosylic quinolone (1,2-dimethyl-6-nitro-4-quinolone "nitroQ") has been found to be more active against nongrowing cells, It exerts an Immediate action on susceptible cells in the lag phase and its activity is reduced when growth occurs. Its activity is not affected by prevention of growth either by withdrawal of nitrogen source or by addition of chloramphenicol. Activity of nitroQ is not proportional to the rate of growth. However, the activity of nitroQ has been found to, depend on concurrent energy metabolism. The antibacterial action of quinolones is accompanied by appearance of long filamentous cells as seen microscopically and by measurement of the increase in average cell size. At bactericidal concentrations. DNA synthesis is preferentially inhibited as compared with RNA and protein synthesis. These results indicate "unbalanced growth" analogous to a variety of conditions which affect DNA synthesis. The close inter-relationship of quinolone activity and DNA synthesis is further supported by the observation that the thymine auxotroph, E. coli 8583, becomes independent of thymine at the same time as it becomes resistant to carboxyQ. However, DNA synthesis is not the sole process affected by quinolones. Both carboxyQ and nitroQ affect the respiration of E. coli 11229 at bactericidal concentrations. She action of quinolones can be completely reversed by removal of drug which suggests that quinolones are not firmly bound to their sensitive site. Partial reversal can also be achieved by addition of precursors of DNA in the thymine auxotroph indicating that inhibition of DNA synthesis is the main if not the sole and primary effect. Resistance to carboxyQ and nitroQ is developed by different mechanisms which adds weight to the division into carboxylic and noncarboxylic quinolones but does not necessarily reflect any fundamental difference in the mode of action.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: W H Holms
• Keywords: Pharmacology
• Date of Award: 1967
• Depositing User: Enlighten Team
• Unique ID: glathesis:1967-72679
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Jun 2019 11:06
• Last Modified: 11 Jun 2019 11:06
• URI: https://theses.gla.ac.uk/id/eprint/72679