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Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes
Karolinska Institute.
Södertörn University, School of Life Sciences. Karolinska Institute.
Swedish University of Agricultural Sciences.
Karolinska Institute / Medical Products Agency.
2006 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 58, no 6, 1160-1167 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim was to study the long-term consequences of 1 week clindamycin administration regarding selection and persistence of resistance, resistance determinants and diversity of the Bacteroides spp. in the intestinal microflora. Methods: A total of 1306 Bacteroides isolates were collected from constitutively cultured faecal samples during a 2 year period from eight healthy volunteers. The strains were identified by biochemical and genotyping methods. MIC values were determined by the agar dilution method and presence of resistance genes was screened by real-time PCR. Results: Ecological changes in the intestinal microflora persisting up to 24 months were recorded after a 7 day clindamycin administration to four healthy volunteers. Compared to a control group, not exposed to clindamycin, an enrichment and stabilization of resistant Bacteroides strains and resistance determinants were discovered up to 2 years after clindamycin exposure. Conclusions: The results indicate that even a short-term antibiotic administration can cause long-term alterations in the commensal microbiota of individual subjects, detectable 2 years after dosing. The recorded selection and persistence of resistant strains and resistance genes, illustrates the importance of increasing our knowledge of the role of the abundant intestinal microbial community as a reservoir for spread of resistance.

Place, publisher, year, edition, pages
2006. Vol. 58, no 6, 1160-1167 p.
National Category
Microbiology Pharmacology and Toxicology Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:sh:diva-14266DOI: 10.1093/jac/dkl420ISI: 000242716600009PubMedID: 17046967ScopusID: 2-s2.0-33845349674OAI: oai:DiVA.org:sh-14266DiVA: diva2:468822
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2011-12-21 Created: 2011-12-20 Last updated: 2017-02-08Bibliographically approved
In thesis
1. Use of microbiomics to study human impacts on complex microbial communities
Open this publication in new window or tab >>Use of microbiomics to study human impacts on complex microbial communities
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The study of bacterial communities in nature is currently a challenge. The majority of bacteria in clinical and environmental samples have not yet been cultured and therefore we cannot fully understand their roles in nature and how the ecological balance in a specific microbial ecosystem can be disrupted. For example, exposure to pollutants in soil and antibiotics in the human gut can have large consequences on microbial populations but the magnitude of these impacts is difficult to assess. In this thesis, a combination of molecular techniques, microbiomics, were used to assess complex microbial communities in soil and the human gut. One goal of this thesis was to study the impact of the toxic compound, 4-chlorophenol, on the soil microbiota. In addition, a specific 4-chlorophenol degrading bacterium, Arthrobacter chlorophenolicus, was monitored in soil. In order to monitor the cells they were chromosomally tagged with marker genes encoding either the green fluorescent protein (the gfp gene) or firefly luciferase (the luc gene). During degradation of high levels of 4-chlorophenol in soil, total cells counts of A. chlorophenolicus cells could be measured by flow cytometry (GFP protein) and the metabolic activity could be measured by lurninometry (luciferase activity). In addition, the relative abundance of A. chlorophenolicus in soil could be measured by terminal restriction fragment length polymorphism (T-RFLP) and a higher relative abundance was detected in soil contaminated with 4chlorophenol compared with non-treated soil. The impacts of 4-chlorophenol and A. chlorophenolicus on the dominant members of the soil microbiota were also assessed by T-RFLP. Another goal of this thesis was to study the impact of a short term antibiotic administration in a long term perspective, using either clindamycin, in a two year study or a triple therapy for eradication of Helicobacter pylori containing clarithromycin and metronidazole, in a four year study, on the human fecal microbiota. Both the total bacterial community and specific populations, i.e. Bacteroides spp. and Enterococcus spp., were monitored by T-RFLP. The Bacteroides populations never returned to their pre-treatment composition after clindamycin exposure during the two year study period. Selection and persistence of resistant Bacteroides clones up to two years after treatment was furthermore detected. In the four year study, Enterococcus populations increased as a response to the clarithromycin and metronidazole treatment. An increase in the levels of antibiotic resistance genes, specific erm genes, conferring resistance to macrolides and lincosamides were detected for up to 2 and 4 years after both types of antibiotic treatments in the respective studies. It was also possible to specifically monitor two probiotic Lactobacillus strains and their transient colonization by T-RFLP. In conclusion, the use of a polyphasic approach with complementary analytical tools made it possible to obtain a comprehensive picture of complex microbial communities. In addition, specific bacteria of interest in complex soil and fecal samples could be monitored using microbiomics approaches.

Place, publisher, year, edition, pages
Stockholm: Karolinska instiutet, 2006. 37 p.
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-31990 (URN)91-7140-960-2 (ISBN)
Public defence
2006-12-15, MB416, Alfred Nobels allé 7, Huddinge, 10:00 (English)
Opponent
Supervisors
Available from: 2017-02-08 Created: 2017-02-08 Last updated: 2017-02-08Bibliographically approved

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