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Mutation frequency and biological cost of resistance in Helicobacter pylori.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
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2001 (English)In: Proc Natl Acad Sci U S A, Vol. 98, no 25, 14607-12 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2001. Vol. 98, no 25, 14607-12 p.
URN: urn:nbn:se:uu:diva-92062OAI: oai:DiVA.org:uu-92062DiVA: diva2:165013
Available from: 2004-09-15 Created: 2004-09-15 Last updated: 2011-06-30Bibliographically approved
In thesis
1. Development and Stability of Antibiotic Resistance
Open this publication in new window or tab >>Development and Stability of Antibiotic Resistance
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibiotic resistance is of current concern. Bacteria have become increasingly resistant to commonly used antibiotics and we are facing a growing resistance problem. The present thesis was aimed at studying the impact of antibiotic treatment on pathogenic bacteria as well as on the normal human microbiota, with focus on resistance development.

Among the factors that affect the appearance of acquired antibiotic resistance, the mutation frequency and biological cost of resistance are of special importance. Our work shows that the mutation frequency in clinical isolates of Helicobacter pylori was generally higher than for other studied bacteria such as Enterobacteriaceae; ¼ of the isolates displayed a mutation frequency higher than Enterobacteriaceae defective mismatch repair mutants and could be regarded as mutator strains.

In H. pylori, clarithromycin resistance confers a biological cost, as measured by decreased competitive ability of the resistant mutants in mice. In clinical isolates, this cost could be reduced, consistent with compensatory evolution stabilizing the presence of the resistant phenotype in the population. Thus, compensation is a clinically relevant phenomenon that can occur in vivo.

Furthermore, our results show that clinical use of antibiotics selects for stable resistance in the human microbiota. This is important for several reasons. First, many commensals occasionally can cause severe disease, even though they are part of the normal microbiota. Therefore, stably resistant populations increase the risk of unsuccessful treatment of such infections. Second, resistance in the normal microbiota might contribute to increased resistance development among pathogens by interspecies transfer of resistant determinants.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 63 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1370
Microbiology, antibiotic resistance, selection, mutation frequency, biological cost of resistance, compensatory evolution, Helicobacter pylori, normal microbiota, Mikrobiologi
National Category
Microbiology in the medical area
urn:nbn:se:uu:diva-4523 (URN)91-554-6026-7 (ISBN)
Public defence
2004-10-08, Hörsalen, Dag Hammarskjölds väg 17, Dag Hammarskjöldsv 17, Uppsala, 13:15
Available from: 2004-09-15 Created: 2004-09-15Bibliographically approved

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