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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

exsA  -  transcriptional regulator ExsA

Pseudomonas aeruginosa PAO1

 
 
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Disease relevance of exsA

  • Results showed that either a retS or an exsA (TTSS) mutation delayed disease progression, as illustrated by reduced severity scores and colonization levels during the first 48 h postinfection [1].
  • RESULTS: For the cytotoxic strain, mutation of either exoU or exoT alone had little effect on virulence, whereas simultaneous mutation of both exoT and exoU or of exsA resulted in a significantly reduced capacity to cause corneal disease [2].
 

High impact information on exsA

  • Although retS mutants caused more severe opacification of central corneas than both the wild type and the exsA mutants, neither mutant caused the peripheral ring opacity commonly associated with wild-type infection, suggesting that the TTSS was involved [1].
  • Strains with mutations in the exsA gene, which encodes a type III regulatory protein, or pscC, which encodes an essential component of the secretion apparatus, were also significantly attenuated [3].
  • Finally, we demonstrate that virulence can be restored in an adenylate cyclase mutant by the overexpression of exsA, which specifically restores expression of the type III secretion system in the absence of a functional cAMP-dependent regulatory network [3].
  • Mutation of exsA reduced both bacterial colonization levels and penetration through the epithelium 3 hours after bacterial inoculation, but only in the 6-hour healing situation, and only for the cytotoxic strain (PA103) [4].
  • Type 3 and 4 strains did not have detectable secretion phenotype; however, some type 4 strains were able to reach a level of cytotoxicity similar to that of type 1 and type 2 strains when complemented in trans by a functional exsA gene [5].
 

Biological context of exsA

  • Virulence of the invasive strain was not reduced by mutation of exsA or of genes encoding the ExsA-regulated secreted proteins [2].
  • The strains, although possessing TTSS genes and exsA, which encodes a positive regulator of the TTSS regulon, showed no transcriptional activation of the exsCBA regulatory operon [6].
  • Expression of the reporter gene was inducible in a low-cation growth environment and required a functional copy of exsA [7].
  • ExsA was produced and purified as a fusion protein, MALA3A2, which was shown to bind specifically to promoter regions that regulated transcription of the exoenzyme S trans-regulatory locus (pC) and a locus located directly downstream of exsA (pD) [8].
  • To ascertain the role of proteins secreted by the type III secretion system (TTSS) in HUVEC killing, defective mutants of PAO1 and PA103 were constructed by plasmid insertion in exsA or pscC genes [9].
 

Anatomical context of exsA

 

Associations of exsA with chemical compounds

  • Cytotoxic strains acquire some of the characteristics of invasive strains when a regulatory gene, exsA, that controls the expression of several extracellular proteins, is inactivated. exsA mutants are not cytotoxic and can be detected within epithelial cells by gentamicin survival assays [11].
  • This was tested by measuring invasion (gentamicin survival) and cytotoxicity (trypan blue staining) of PA103 mutants deficient in specific exsA-regulated proteins and by testing the effect of drugs that inhibit invasion for their effect on cytotoxicity [11].
 

Other interactions of exsA

  • A fimV mutant was unable to induce the expression of exoS, exoT and exsA genes under type III inducing conditions, thus exhibiting a defect in type III protein secretion [12].
  • Our data indicate that the untranslated exsB region of the trans-regulatory locus mRNA mediates either the stability or the translation of exsA [13].
  • Homology studies suggested that the region encoded three regulatory genes, exsC, exsB, and exsA [14].
 

Analytical, diagnostic and therapeutic context of exsA

  • Time-lapse video microscopy revealed that retS mutants, compared to exsA mutants, had a reduced capacity to access, and move along, the basal cell surfaces of corneal epithelial cell monolayers [15].

References

  1. Type III secretion-dependent modulation of innate immunity as one of multiple factors regulated by Pseudomonas aeruginosa RetS. Zolfaghar, I., Evans, D.J., Ronaghi, R., Fleiszig, S.M. Infect. Immun. (2006) [Pubmed]
  2. Contribution of ExsA-regulated factors to corneal infection by cytotoxic and invasive Pseudomonas aeruginosa in a murine scarification model. Lee, E.J., Cowell, B.A., Evans, D.J., Fleiszig, S.M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  3. An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Smith, R.S., Wolfgang, M.C., Lory, S. Infect. Immun. (2004) [Pubmed]
  4. Role of Pseudomonas aeruginosa ExsA in penetration through corneal epithelium in a novel in vivo model. Lee, E.J., Evans, D.J., Fleiszig, S.M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  5. Genotypic and phenotypic analysis of type III secretion system in a cohort of Pseudomonas aeruginosa bacteremia isolates: evidence for a possible association between O serotypes and exo genes. Berthelot, P., Attree, I., Plésiat, P., Chabert, J., de Bentzmann, S., Pozzetto, B., Grattard, F. J. Infect. Dis. (2003) [Pubmed]
  6. Expression of ExsA in trans confers type III secretion system-dependent cytotoxicity on noncytotoxic Pseudomonas aeruginosa cystic fibrosis isolates. Dacheux, D., Attree, I., Toussaint, B. Infect. Immun. (2001) [Pubmed]
  7. Transcriptional analysis of the Pseudomonas aeruginosa exoenzyme S structural gene. Yahr, T.L., Hovey, A.K., Kulich, S.M., Frank, D.W. J. Bacteriol. (1995) [Pubmed]
  8. Analyses of the DNA-binding and transcriptional activation properties of ExsA, the transcriptional activator of the Pseudomonas aeruginosa exoenzyme S regulon. Hovey, A.K., Frank, D.W. J. Bacteriol. (1995) [Pubmed]
  9. Type III secretion-mediated killing of endothelial cells by Pseudomonas aeruginosa. Saliba, A.M., Filloux, A., Ball, G., Silva, A.S., Assis, M.C., Plotkowski, M.C. Microb. Pathog. (2002) [Pubmed]
  10. Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct genotypes at the loci encoding exoenzyme S. Fleiszig, S.M., Wiener-Kronish, J.P., Miyazaki, H., Vallas, V., Mostov, K.E., Kanada, D., Sawa, T., Yen, T.S., Frank, D.W. Infect. Immun. (1997) [Pubmed]
  11. Pseudomonas aeruginosa invasion and cytotoxicity are independent events, both of which involve protein tyrosine kinase activity. Evans, D.J., Frank, D.W., Finck-Barbançon, V., Wu, C., Fleiszig, S.M. Infect. Immun. (1998) [Pubmed]
  12. The truA gene of Pseudomonas aeruginosa is required for the expression of type III secretory genes. Ahn, K.S., Ha, U., Jia, J., Wu, D., Jin, S. Microbiology (Reading, Engl.) (2004) [Pubmed]
  13. Functional analysis of exsC and exsB in regulation of exoenzyme S production by Pseudomonas aeruginosa. Goranson, J., Hovey, A.K., Frank, D.W. J. Bacteriol. (1997) [Pubmed]
  14. Cloning and sequence analysis of a trans-regulatory locus required for exoenzyme S synthesis in Pseudomonas aeruginosa. Frank, D.W., Iglewski, B.H. J. Bacteriol. (1991) [Pubmed]
  15. Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms. Zolfaghar, I., Angus, A.A., Kang, P.J., To, A., Evans, D.J., Fleiszig, S.M. Microbes Infect. (2005) [Pubmed]
 
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