Lethality of quinolones against Mycobacterium smegmatis in the presence or absence of chloramphenicol.
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.
Malik
Muhammad
M
Public Health Research Institute, 225 Warren St., Newark, NJ 07103, USA.
Lu
Tao
T
Zhao
Xilin
X
Singh
Anubha
A
Hattan
Christopher M
CM
Domagala
John
J
Kerns
Robert
R
Drlica
Karl
K
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
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D002701:Chloramphenicol