Twin-arginine translocation system (tat) mutants of Salmonella are attenuated due to envelope defects, not respiratory defects

Maureen Craig, Adam Y. Sadik, Yekaterina A. Golubeva, Avital Tidhar, James M. Slauch

Research output: Contribution to journalArticle

Abstract

The twin-arginine translocation system (Tat) transports folded proteins across the cytoplasmic membrane and is critical to virulence in Salmonella and other pathogens. Experimental and bioinformatic data indicate that 30 proteins are exported via Tat in SalmonellaTyphimurium. However, there are no data linking specific Tat substrates with virulence. We inactivated every Tat-exported protein and determined the virulence phenotype of mutant strains. Although a tat mutant is highly attenuated, no single Tat-exported substrate accounts for this virulence phenotype. Rather, the attenuation is due primarily to envelope defects caused by failure to translocate three Tat substrates, the N-acetylmuramoyl-l-alanine amidases, AmiA and AmiC, and the cell division protein, SufI. Strikingly, neither the amiA amiC nor the sufI mutations alone conferred any virulence defect. Although AmiC and SufI have previously been localized to the divisome, the synthetic phenotypes observed are the first to suggest functional overlap. Many Tat substrates are involved in anaerobic respiration, but we show that a mutant completely deficient in anaerobic respiration retains full virulence in both the oral and systemic phases of infection. Similarly, an obligately aerobic mutant is fully virulent. These results suggest that in the classic mouse model of infection, S. Typhimurium is replicating only in aerobic environments.

Original languageEnglish (US)
Pages (from-to)887-902
Number of pages16
JournalMolecular Microbiology
Volume89
Issue number5
DOIs
StatePublished - Sep 1 2013

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Salmonella
Virulence
Phenotype
Respiration
Amidohydrolases
Proteins
Twin-Arginine-Translocation System
Infection
Computational Biology
Alanine
Cell Division
Carrier Proteins
Cell Membrane
Mutation

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Twin-arginine translocation system (tat) mutants of Salmonella are attenuated due to envelope defects, not respiratory defects. / Craig, Maureen; Sadik, Adam Y.; Golubeva, Yekaterina A.; Tidhar, Avital; Slauch, James M.

In: Molecular Microbiology, Vol. 89, No. 5, 01.09.2013, p. 887-902.

Research output: Contribution to journalArticle

Craig, Maureen ; Sadik, Adam Y. ; Golubeva, Yekaterina A. ; Tidhar, Avital ; Slauch, James M. / Twin-arginine translocation system (tat) mutants of Salmonella are attenuated due to envelope defects, not respiratory defects. In: Molecular Microbiology. 2013 ; Vol. 89, No. 5. pp. 887-902.
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