Lower concentrations of clarithromycin suppress urease activity, motility, and binding to gastric epithelial cells in Helicobacter pylori isolates.
BACKGROUND
Our previous study showed that histological scores of gastric mucosal inflammation and Helicobacter pylori density decreased even in patients who failed to eradicate Helicobacter pylori after antimicrobial therapy including clarithromycin. This may reflect indirect suppressive effects of lower concentrations of clarithromycin on Helicobacter pylori, as suggested in other Gram-negative rod infections.


OBJECTIVE
To investigate whether clarithromycin suppresses virulence factors of Helicobacter pylori at sub-minimal inhibitory concentration.


METHODS
Six clarithromycin-susceptible Helicobacter pylori isolates and 7 clarithromycin-resistant isolates were obtained from patients with peptic ulcer disease. These isolates were analysed for urease activity, motility, and ability to bind to gastric epithelial cells after they were incubated with or without clarithromycin at sub-minimal inhibitory concentrations.


RESULTS
Incubation of Helicobacter pylori isolates with clarithromycin at sub-minimal inhibitory concentrations reduced urease activity motility, and binding to gastric epithelial cells in a dose-dependent manner. These findings were observed both in clarithromycin-susceptible and resistant strains.


CONCLUSIONS
Suppressive effects of clerithromycin on virulence factors of Helicobacter pylori at sub-minimal inhibitory concentrations may be associated with observed attenuation of gastric inflammation and Helicobacter pylori density in patients who failed in bacterial eradication after triple therapy including clarithromycin.
Nobata
K
K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Ina
K
K
Ohta
M
M
Kawamura-Sato
K
K
Tsuzuki
T
T
Ando
T
T
Kusugami
K
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001667:Binding, Competitive / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use*; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D010437:Peptic Ulcer / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D013270:Stomach / Q000166:cytology*; D016896:Treatment Outcome; D014510:Urease / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D014510:Urease; D017291:Clarithromycin