Digitala Vetenskapliga Arkivet

Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
The Physiological Cost of Antibiotic Resistance
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
2003 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Becoming antibiotic resistant is often associated with fitness costs for the resistant bacteria. This is seen as a loss of competitiveness against the antibiotic-sensitive wild-type in an antibiotic-free environment. In this study, the physiological alterations associated with fitness cost of antibiotic resistance in vitro (in the laboratory medium), and in vivo (in a mouse infection model), are identified in the model system of fusidic acid resistant (FusR) Salmonella enterica serovar Typhimurium.

FusR mutants have mutations in fusA, the gene that encodes translation elongation factor G (EF-G). FusR EF-G has a slow rate of regeneration of active EF-G·GTP off the ribosome, resulting in a slow rate of protein synthesis. The low fitness of FusR mutants in vitro, and in vivo, can be explained in part by a slow rate of protein synthesis and resulting slow growth. However, some FusR mutants with normal rates of protein synthesis still suffer from reduced fitness in vivo. We observed that FusR mutants have perturbed levels of the global regulatory molecule ppGpp. One consequence of this is an inefficient induction of RpoS, a regulator of general stress reponse and an important virulence factor for Salmonella. In addition, we found that FusR mutants have reduced amounts of heme, a co-factor of catalases and cytochromes. As a consequence of the heme defect, FusR mutants have a reduced ability to withstand oxidative stress and a low rate of aerobic respiration.

The pleiotropic phenotypes of FusR mutants suggest that antibiotic resistance can be associated with broad changes in bacterial physiology. Knowledge of physiological alterations that reduce the fitness of antibiotic-resistant mutants can be useful in identifying novel targets for antimicrobial agents. Drugs that alter the levels of global transcriptional regulators such as ppGpp or RpoS deserve attention as potential antimicrobial agents. Finally, the observation that FusR mutants have increased sensitivity to several unrelated classes of antibiotics suggests that the identification of physiological cost of resistance can help in optimizing treatment of resistant bacterial populations.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis , 2003. , s. 63
Serie
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 904
Nyckelord [en]
Microbiology, fusidic acid, fitness cost, protein synthesis, EF-G, ppGpp, RpoS, oxidative stress, heme
Nyckelord [sv]
Mikrobiologi
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:uu:diva-3761ISBN: 91-554-5794-0 (tryckt)OAI: oai:DiVA.org:uu-3761DiVA, id: diva2:163601
Disputation
2003-12-12, C8:305, Biomedical Center, Uppsala, 13:00
Opponent
Handledare
Tillgänglig från: 2003-11-21 Skapad: 2003-11-21 Senast uppdaterad: 2022-03-11Bibliografiskt granskad
Delarbeten
1. Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
Öppna denna publikation i ny flik eller fönster >>Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
2000 Ingår i: Molecular Microbiology, Vol. 37, nr 1, s. 98-107Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-91024 (URN)
Tillgänglig från: 2003-11-21 Skapad: 2003-11-21Bibliografiskt granskad
2. Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction
Öppna denna publikation i ny flik eller fönster >>Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction
Visa övriga...
2003 Ingår i: Antimicrobial Agents and Chemotherapy, Vol. 47, nr 12Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-91025 (URN)
Tillgänglig från: 2003-11-21 Skapad: 2003-11-21Bibliografiskt granskad
3. Reduced levels of heme and respiration rate in elongation factor G mutants of Salmonella enterica serovar Typhimurium
Öppna denna publikation i ny flik eller fönster >>Reduced levels of heme and respiration rate in elongation factor G mutants of Salmonella enterica serovar Typhimurium
Manuskript (Övrigt vetenskapligt)
Identifikatorer
urn:nbn:se:uu:diva-91026 (URN)
Tillgänglig från: 2003-11-21 Skapad: 2003-11-21 Senast uppdaterad: 2010-01-13Bibliografiskt granskad
4. Hypersensitivity of fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium to several classes of antibiotics
Öppna denna publikation i ny flik eller fönster >>Hypersensitivity of fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium to several classes of antibiotics
Manuskript (Övrigt vetenskapligt)
Identifikatorer
urn:nbn:se:uu:diva-91027 (URN)
Tillgänglig från: 2003-11-21 Skapad: 2003-11-21 Senast uppdaterad: 2010-01-13Bibliografiskt granskad

Open Access i DiVA

fulltext(619 kB)2545 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 619 kBChecksumma SHA-1
950448a378c63c24835542d342a17f509ad1ec7f3d09e4530c4f3ab39323720055176824
Typ fulltextMimetyp application/pdf

Av organisationen
Institutionen för cell- och molekylärbiologi
Mikrobiologi inom det medicinska området

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 2545 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

isbn
urn-nbn

Altmetricpoäng

isbn
urn-nbn
Totalt: 2079 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf