Pathophysiology of antibiotic resistance: clarithromycin.
Resistance of Helicobacter pylori to antibiotics ranges from 3% to 10% and may exceed these levels in some countries. The pathophysiology of clarithromycin resistance is reviewed, including the mode of action by which the antibiotic inhibits protein synthesis and the mechanism of resistance, which involves a mutation at position 2142 or 2143 in the V loop domain of the 23SrRNA genes. Mutations of A2142G confer a higher minimum inhibitory concentration than mutations of A2143G. The former demonstrate cross-resistance to macrolide, lincosamide and streptogramin antibiotics, whereas the latter are susceptible to streptogramin B. In vitro mutagenesis combined with natural transformation were used to create several types of clarithromycin-resistant mutants. H pylori strains with A2142G and A2143G mutations had a higher growth rate than those with A2142C, A2143 or A2142T mutations. Data from this study indicate why clarithromycin-resistant clinical isolates of H pylori are more likely to have A2142G or A2143G mutations and only occassionally A2142C mutations.
Taylor
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Department of Medical Microbiology and Immunization, University of Alberta, Edmonton, Canada. Diane.Taylor@ualberta.ca
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D017291:Clarithromycin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D012329:RNA, Bacterial / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012329:RNA, Bacterial; D017291:Clarithromycin