Digitala Vetenskapliga Arkivet

Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet 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 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis , 2003. , s. 63
Serie
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 904
Emneord [en]
Microbiology, fusidic acid, fitness cost, protein synthesis, EF-G, ppGpp, RpoS, oxidative stress, heme
Emneord [sv]
Mikrobiologi
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-3761ISBN: 91-554-5794-0 (tryckt)OAI: oai:DiVA.org:uu-3761DiVA, id: diva2:163601
Disputas
2003-12-12, C8:305, Biomedical Center, Uppsala, 13:00
Opponent
Veileder
Tilgjengelig fra: 2003-11-21 Laget: 2003-11-21 Sist oppdatert: 2022-03-11bibliografisk kontrollert
Delarbeid
1. Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
Åpne denne publikasjonen i ny fane eller vindu >>Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
2000 Inngår i: Molecular Microbiology, Vol. 37, nr 1, s. 98-107Artikkel i tidsskrift (Fagfellevurdert) Published
Identifikatorer
urn:nbn:se:uu:diva-91024 (URN)
Tilgjengelig fra: 2003-11-21 Laget: 2003-11-21bibliografisk kontrollert
2. Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction
Åpne denne publikasjonen i ny fane eller vindu >>Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction
Vise andre…
2003 Inngår i: Antimicrobial Agents and Chemotherapy, Vol. 47, nr 12Artikkel i tidsskrift (Fagfellevurdert) Published
Identifikatorer
urn:nbn:se:uu:diva-91025 (URN)
Tilgjengelig fra: 2003-11-21 Laget: 2003-11-21bibliografisk kontrollert
3. Reduced levels of heme and respiration rate in elongation factor G mutants of Salmonella enterica serovar Typhimurium
Åpne denne publikasjonen i ny fane eller vindu >>Reduced levels of heme and respiration rate in elongation factor G mutants of Salmonella enterica serovar Typhimurium
Manuskript (Annet vitenskapelig)
Identifikatorer
urn:nbn:se:uu:diva-91026 (URN)
Tilgjengelig fra: 2003-11-21 Laget: 2003-11-21 Sist oppdatert: 2010-01-13bibliografisk kontrollert
4. Hypersensitivity of fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium to several classes of antibiotics
Åpne denne publikasjonen i ny fane eller vindu >>Hypersensitivity of fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium to several classes of antibiotics
Manuskript (Annet vitenskapelig)
Identifikatorer
urn:nbn:se:uu:diva-91027 (URN)
Tilgjengelig fra: 2003-11-21 Laget: 2003-11-21 Sist oppdatert: 2010-01-13bibliografisk kontrollert

Open Access i DiVA

fulltekst(619 kB)2545 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 619 kBChecksum SHA-1
950448a378c63c24835542d342a17f509ad1ec7f3d09e4530c4f3ab39323720055176824
Type fulltextMimetype application/pdf

Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 2545 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

isbn
urn-nbn

Altmetric

isbn
urn-nbn
Totalt: 2079 treff
RefereraExporteraLink to record
Permanent link

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