uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Show others and affiliations
2003 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 47, no 12, 3743-3749 p.Article in journal (Refereed) Published
Abstract [en]

Mutants of Salmonella enterica serovar Typhimurium resistant to fusidic acid (Fusr) have mutations in fusA, the gene encoding translation elongation factor G (EF-G). Most Fusr mutants have reduced fitness in vitro and in vivo, in part explained by mutant EF-G slowing the rate of protein synthesis and growth. However, some Fusr mutants with normal rates of protein synthesis still suffer from reduced fitness in vivo. As shown here, Fusr mutants could be similarly ranked in their relative fitness in mouse infection models, in a macrophage infection model, in their relative hypersensitivity to hydrogen peroxide in vivo and in vitro, and in the amount of RpoS production induced upon entry into the stationary phase. We identify a reduced ability to induce production of RpoS (sigmas) as a defect associated with Fusr strains. Because RpoS is a regulator of the general stress response, and an important virulence factor in Salmonella, an inability to produce RpoS in appropriate amounts can explain the low fitness of Fusr strains in vivo. The unfit Fusr mutants also produce reduced levels of the regulatory molecule ppGpp in response to starvation. Because ppGpp is a positive regulator of RpoS production, we suggest that a possible cause of the reduced levels of RpoS is the reduction in ppGpp production associated with mutant EF-G. The low fitness of Fusr mutants in vivo suggests that drugs that can alter the levels of global regulators of gene expression deserve attention as potential antimicrobial agents.

Place, publisher, year, edition, pages
2003. Vol. 47, no 12, 3743-3749 p.
National Category
Microbiology in the medical area
URN: urn:nbn:se:uu:diva-47239DOI: 10.1128/AAC.47.12.3743-3749.2003PubMedID: 14638476OAI: oai:DiVA.org:uu-47239DiVA: diva2:75146
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-07-18Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Hughes, Diarmaid
By organisation
Department of Cell and Molecular Biology
In the same journal
Antimicrobial Agents and Chemotherapy
Microbiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 272 hits
ReferencesLink to record
Permanent link

Direct link