Characterization of resistance to quinolones, sulfonamide and trimethoprim in Campylobacter jejuni as well as to macrolides in the related bacterium, Helicobacter pylori
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Gastroenteritis caused by C. jejuni is usually a mild to moderate self-limiting disease. Treatment is recommended in some cases. In recent years, quinolones have been increasingly used to treat acute bacterial enteritis. Quinolone resistance in clinical isolates of C. jejuni in Sweden increased more than 20-fold at the beginning of 1990s. Quinolone resistance in C. jejuni was found to be associated with chromosomal mutations leading to a Thr-86-to Ile substitution in the gyrA gene and an Arg-139-to Gln substitution in the parC gene.
Sulfonamides and trimethoprim have always been considered as inefficient antimicrobial agents for the treatment of Campylobacter infections. Detailed studies regarding the molecular basis of resistance to sulfonamide and trimethoprim in C. jejuni are lacking. Further data about the molecular basis of resistance might be a good contribution to the general understanding of the nathogenicity of C. jejuni. Resistance of C. jejuni to a high-level of trimethoprim was found to be due to the acquisition of dfr genes expressing-drug-resistant variants of the target enzyme, dihydrofolate reductase (DHFR). The most commonly found gene was dfr1 but another gene, dfr9,was also detected. These genes were observed to be chromosomally located in an integron and a transposon context, respectively. In some cases, a 90 bp repeat-containing variant of the dfr1 gene was detected. Moreover, in 5% of the examined C. jejuni strains, the repeat-containing dfr 1 variant was found to occur in the form of two cassettes in tandem located in an integron context. The existence of the 90 bp repeat within the coding sequence of the dfr 1 gene was found to play a role in the adaptability of C. jejuni isolates to the variation in the selection pressure induced by trimethoprim.
The acquisition of sulfonamide resistance, however, was found to be associated with the mutational substitution of four amino acid residues in the chromosomal folP gene of C. jejuni. Kinetic measurements established different affinities of sulfonamide for the DHPS enzyme isolated from the resistant and susceptible strains.
Treatment regimen with clarithromycin has been found to cure H. pylori infection efficiently. The development of macrolide resistance should be monitored during the course of the treatment. Transition mutations in the 23S rRNA gene at locations corresponding to macrolide resistance in other bacteria were observed. No other mechanisms of resistance were detected.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 58 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 202
Research subject Pharmaceutical Microbiology
IdentifiersURN: urn:nbn:se:uu:diva-962ISBN: 91-554-4427-XOAI: oai:DiVA.org:uu-962DiVA: diva2:173299
1999-05-07, lecture room C4:301, Biomedical Centre (BMC), Uppsala, Uppsala, 10:00