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| 2. |
- Gustafsson, Ingegerd, et al.
(författare)
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Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage
- 2003
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 52:4, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We examined how prolonged antibiotic treatment affected the resistance and mutation frequency of human microflora isolated from intestine (Escherichia coli, enterococci spp.), pharynx (alpha-streptococci) and nostril (coagulase-negative staphylococci, CoNS).METHODS: Samples were collected from patients at the Center of Cystic Fibrosis (n=18) and the haematology ward (n=18) of the University Hospital, Uppsala, Sweden. The individually used amount of antibiotics for 1 year was recorded as the defined daily dose (DDD). Primary health care patients (n=30), with no antibiotic treatment for 1 year before sampling, were used as controls. Three isolates of each bacterium from each patient were examined. Antibiotic susceptibilities were determined by disc diffusion. Mutation frequencies to rifampicin resistance were measured on 30 independent cultures of each bacterial species from each individual by plating on rifampicin agar plates. For alpha-streptococci the mutation frequency to streptomycin resistance was also determined.RESULTS: Isolates from patients with high antibiotic use showed a pronounced shift towards increased resistance and a small but significant increase in the mutation frequency compared with isolates from the controls. For E. coli, enterococci and CoNS the increase in geometric mean mutation frequency in the patient group was 3-, 1.8- and 1.5-fold, respectively (P values 0.0001, 0.016 and 0.012). For alpha-streptococci there was a significant difference in geometric mean mutation frequency between patient and control groups for streptomycin resistance (P=0.024) but not for rifampicin resistance (P=0.74).CONCLUSIONS: High antibiotic use selected for commensals with highly increased resistance and a slight increase in mutation frequency.
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| 3. |
- Lundin, A., et al.
(författare)
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Slow genetic divergence of Helicobacter pylori strains during long-term colonization
- 2005
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 73:8, s. 4818-4822
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Tidskriftsartikel (refereegranskat)abstract
- The genetic variability of Helicobacter pylori is known to be high compared to that of many other bacterial species. H. pylori is adapted to the human stomach, where it persists for decades, and adaptation to each host results in every individual harboring a distinctive bacterial population. Although clonal variants may exist within such a population, all isolates are generally genetically related and thus derived from a common ancestor. We sought to determine the rate of genetic change of H. pylori over 9 years in two asymptomatic adult patients. Arbitrary primed PCR confirmed the relatedness of individual subclones within a patient. Furthermore, sequencing of 10 loci (similar to 6,000 bp) in three subclones per time and patient revealed only two base pair changes among the subclones from patient I. All sequences were identical among the patient II subclones. However, PCR amplification of the highly divergent gene amiA revealed great variation in the size of the gene between the subclones within each patient. Thus, both patients harbored a single strain with clonal variants at both times. We also studied genetic changes in culture- and mouse-passaged strains, and under both conditions no genetic divergence was found. These results suggest that previous estimates of the rate of genetic change in H. pylori within an individual might be overestimates.
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| 4. |
- Lundin, Annelie, et al.
(författare)
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The NudA protein in the gastric pathogen Helicobacter pylori is an ubiquitous and constitutively expressed dinucleoside polyphosphate hydrolase
- 2003
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 278:14, s. 12574-12578
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The gastric pathogen Helicobacter pylori harbors one Nudix hydrolase, NudA, that belongs to the nucleoside polyphosphate hydrolase subgroup. In this work, the enzymatic activity of purified recombinant NudA protein was analyzed on a number of nucleoside polyphosphates. This predicted 18.6-kDa protein preferably hydrolyzes diadenosine tetraphosphate, Ap(4)A at a k(cat) of 0.15 s(-1) and a K(m) of 80 microm, resulting in an asymmetrical cleavage of the molecule into ATP and AMP. To study the biological role of this enzyme in H. pylori, an insertion mutant was constructed. There was a 2-7-fold decrease in survival of the mutant as compared with the wild type after hydrogen peroxide exposure but no difference in survival after heat shock or in spontaneous mutation frequency. Western blot analyses revealed that NudA is constitutively expressed in H. pylori at different growth stages and during stress, which would indicate that this protein has a housekeeping function. Given that H. pylori is a diverse species and that all the H. pylori strains tested in this study harbor the nudA gene and show protein expression, we consider NudA to be an important enzyme in this bacterium.
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| 6. |
- Sjölund, Maria, et al.
(författare)
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Long-term persistence of resistant Enterococcus species after antibiotics to eradicate Helicobacter pylori
- 2003
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 139:6, s. 483-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Antibiotic treatment selects for resistance not only in the pathogen to which it is directed but also in the indigenous microflora. OBJECTIVE: To determine whether a widely used regimen (clarithromycin, metronidazole, and omeprazole) for Helicobacter pylori eradication affects resistance development in enterococci. DESIGN: Cohort study. SETTING: Endoscopy units at 3 community hospitals in Sweden. PATIENTS: 5 consecutive dyspeptic patients who were colonized with H. pylori, had endoscopy-confirmed duodenal ulcer, and received antibiotic treatment, and 5 consecutive controls with dyspepsia but no ulcer who did not receive treatment. MEASUREMENTS: Fecal samples were obtained from patients and controls before, immediately after, 1 year after, and 3 years after treatment. From each patient and sample, enterococci were isolated and analyzed for DNA fingerprint, clarithromycin susceptibility, and presence of the erm(B) gene. RESULTS: In treated patients, all enterococci isolated immediately after treatment showed high-level clarithromycin resistance due to erm(B). In 3 patients, resistant enterococci persisted for 1 to 3 years after treatment. No resistance developed among controls. CONCLUSION: A common H. pylori treatment selects for highly resistant enterococci that can persist for at least 3 years without further selection.
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| 7. |
- Sjölund, Maria, et al.
(författare)
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Persistence of resistant Staphylococcus epidermidis after single course of clarithromycin
- 2005
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 11:9, s. 1389-1393
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Tidskriftsartikel (refereegranskat)abstract
- We examined how a common therapy that includes clarithromycin affects normally colonizing Staphylococcus epidermidis. Samples from the nostrils of 5 patients receiving therapy were collected before, immediately after, 1 year after, and 4 years after treatment. From each patient and sample, S. epidermidis strains were isolated and analyzed for clarithromycin susceptibility and presence of the erm(C) gene. We show that macrolide-resistant strains of S. epidermidis were selected during therapy and that the same resistant strain may persist for 4 years, in the absence of further antimicrobial treatment.
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