title: 4-Quinolone bactericidal mechanisms.
abstract: The bactericidal activity of nalidixic acid against Escherichia coli strain KL16 in nutrient broth was abolished by the addition of rifampicin. Cells suspended in phosphate-buffered normal saline (PBS) were also not killed by nalidixic acid. Experiments with modern 4-quinolones showed their activities varied according to the conditions under which they were tested. Rifampicin did not affect the concentration at which ofloxacin became bactericidal in nutrient broth, but did limit the extent of ofloxacin-induced death. However, rifampicin produced a 10-fold increase in the concentration at which ciprofloxacin became bactericidal in nutrient broth, and completely abolished the bactericidal activity of norfloxacin. Unlike nalidixic acid all of the modern 4-quinolones killed cells suspended in PBS. Based on these results it was possible to differentiate 3 processes by which 4-quinolones induced death. Mechanism A was only active against dividing bacteria and required RNA and protein synthesis; it was therefore not active against bacteria suspended in PBS and was inhibited in nutrient broth by the addition of rifampicin. Mechanism B required neither RNA nor protein synthesis and was also active against non-dividing bacteria; it was therefore not inhibited by rifampicin nor by suspending bacteria in PBS. Mechanism C killed non-dividing bacteria, but required protein and RNA synthesis: it therefore functioned in PBS, but was inhibited by rifampicin.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of London, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Howard
authors.forename: R J
authors.initials: RJ
authors.lastname: Pinney
authors.forename: J T
authors.initials: JT
authors.lastname: Smith
mesh_terms: D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010710:Phosphates / Q000494:pharmacology; D012329:RNA, Bacterial / Q000096:biosynthesis; D012293:Rifampin / Q000494:pharmacology
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D003470:Culture Media; D010710:Phosphates; D012329:RNA, Bacterial; D012293:Rifampin