title: Lethality of quinolones against Mycobacterium smegmatis in the presence or absence of chloramphenicol.
abstract: Quinolones were examined for rapid lethal activity against Mycobacterium smegmatis in the presence and absence of chloramphenicol, an inhibitor of protein synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents enhanced rapid killing. With the surprising exception of moxifloxacin, higher quinolone concentrations were required for lethal activity in the presence of chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone dimers, which represent quinolones with large C-7 substituents, showed modest bacteriostatic activity. Unlike other quinolones, the dimers failed to display lethal activity. The insensitivity of moxifloxacin to chloramphenicol has not been observed with other bacteria and may therefore reflect unique aspects of mycobacterial gyrase.
authors.affiliation: Public Health Research Institute, 225 Warren St., Newark, NJ 07103, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Malik
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhao
authors.forename: Anubha
authors.initials: A
authors.lastname: Singh
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hattan
authors.forename: John
authors.initials: J
authors.lastname: Domagala
authors.forename: Robert
authors.initials: R
authors.lastname: Kerns
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002701:Chloramphenicol / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D002701:Chloramphenicol