This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tamayo, R.
Right arrow Articles by Gunn, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tamayo, R.
Right arrow Articles by Gunn, J. S.

 Previous Article  |  Next Article 

Infection and Immunity, December 2002, p. 6770-6778, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6770-6778.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification and Genetic Characterization of PmrA-Regulated Genes and Genes Involved in Polymyxin B Resistance in Salmonella enterica Serovar Typhimurium

Rita Tamayo, Sara S. Ryan, Andrea J. McCoy,{dagger} and John S. Gunn*

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-7758

Received 9 May 2002/ Returned for modification 24 July 2002/ Accepted 21 August 2002

Salmonella enterica serovar Typhimurium encounters antimicrobial peptides (AP) within the phagosomes of professional phagocytes and at intestinal mucosal surfaces. Salmonella serovar Typhimurium utilizes the two-component regulatory system PmrA-PmrB, which is activated in response to the environmental conditions encountered in vivo, to regulate resistance to several AP, including polymyxin B (PM). Random MudJ transposon mutagenesis was used to identify PmrA-PmrB-regulated genes, as well as genetic loci necessary for PM resistance. Three different phenotypic classes of genes were identified: those necessary for PM resistance and regulated by PmrA, those necessary for PM resistance and not regulated by PmrA, and PmrA-regulated genes not required for PM resistance. Loci identified as necessary for PM resistance showed between 6- and 192-fold increased sensitivities to PM, and transposon insertion sites include surA, tolB, and gnd. PmrA-regulated loci identified included dgoA and yibD and demonstrated 500- and 2,500-fold activation by PmrA, respectively. The role of the identified loci in aminoarabinose modification of lipid A was determined by paper chromatography. The gnd mutant demonstrated a loss of aminoarabinose from lipid A, which was suggested to be due to a polar effect on the downstream gene pmrE. The remaining PMs mutants (surA and tolB), as well as the two PmrA-regulated gene (yibD and dgoA) mutants, retained aminoarabinose on lipid A. yibD, dgoA, and gnd (likely affecting pmrE) played no role in PmrA-regulated resistance to high iron concentrations, while surA and tolB mutations grew poorly on high iron media. All PMs mutants identified in this study demonstrated a defect in virulence compared to wild-type Salmonella serovar Typhimurium when administered orally to mice, while the PmrA-regulated gene (yibD and dgoA) mutants showed normal virulence in mice. These data broaden our understanding of in vivo gene regulation, lipopolysaccharide modification, and mechanisms of resistance to AP in enteric bacteria.

* Corresponding author. Mailing address: University of Texas Health Science Center at San Antonio, Department of Microbiology, MC7758, 7703 Floyd Curl Dr., San Antonio, TX 77229-3900. Phone: (210) 567-3973. Fax: (210) 567-3795. E-mail: gunnj{at}uthscsa.edu.

Editor: V. J. DiRita

{dagger} Present address: Molecular and Cell Biology, USUHS, Herbert School of Medicine, Bethesda, MD 20814.

Infection and Immunity, December 2002, p. 6770-6778, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6770-6778.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sikora, A. E., Beyhan, S., Bagdasarian, M., Yildiz, F. H., Sandkvist, M. (2009). Cell Envelope Perturbation Induces Oxidative Stress and Changes in Iron Homeostasis in Vibrio cholerae. J. Bacteriol. 191: 5398-5408 [Abstract] [Full Text]  
  • Lamarche, M. G., Kim, S.-H., Crepin, S., Mourez, M., Bertrand, N., Bishop, R. E., Dubreuil, J. D., Harel, J. (2008). Modulation of Hexa-Acyl Pyrophosphate Lipid A Population under Escherichia coli Phosphate (Pho) Regulon Activation. J. Bacteriol. 190: 5256-5264 [Abstract] [Full Text]  
  • Wang, W.-B., Chen, I-C., Jiang, S.-S., Chen, H.-R., Hsu, C.-Y., Hsueh, P.-R., Hsu, W.-B., Liaw, S.-J. (2008). Role of RppA in the Regulation of Polymyxin B Susceptibility, Swarming, and Virulence Factor Expression in Proteus mirabilis. Infect. Immun. 76: 2051-2062 [Abstract] [Full Text]  
  • Altman, E., Segal, G. (2008). The Response Regulator CpxR Directly Regulates Expression of Several Legionella pneumophila icm/dot Components as Well as New Translocated Substrates. J. Bacteriol. 190: 1985-1996 [Abstract] [Full Text]  
  • Kindrachuk, J., Paur, N., Reiman, C., Scruten, E., Napper, S. (2007). The PhoQ-Activating Potential of Antimicrobial Peptides Contributes to Antimicrobial Efficacy and Is Predictive of the Induction of Bacterial Resistance. Antimicrob. Agents Chemother. 51: 4374-4381 [Abstract] [Full Text]  
  • Murray, S. R., Ernst, R. K., Bermudes, D., Miller, S. I., Low, K. B. (2007). PmrA(Con) Confers pmrHFIJKL-Dependent EGTA and Polymyxin Resistance on msbB Salmonella by Decorating Lipid A with Phosphoethanolamine. J. Bacteriol. 189: 5161-5169 [Abstract] [Full Text]  
  • McPhee, J. B., Bains, M., Winsor, G., Lewenza, S., Kwasnicka, A., Brazas, M. D., Brinkman, F. S. L., Hancock, R. E. W. (2006). Contribution of the PhoP-PhoQ and PmrA-PmrB Two-Component Regulatory Systems to Mg2+-Induced Gene Regulation in Pseudomonas aeruginosa. J. Bacteriol. 188: 3995-4006 [Abstract] [Full Text]  
  • Skovierova, H., Rowley, G., Rezuchova, B., Homerova, D., Lewis, C., Roberts, M., Kormanec, J. (2006). Identification of the {sigma}E regulon of Salmonella enterica serovar Typhimurium.. Microbiology 152: 1347-1359 [Abstract] [Full Text]  
  • Kim, S.-H., Jia, W., Parreira, V. R., Bishop, R. E., Gyles, C. L. (2006). Phosphoethanolamine substitution in the lipid A of Escherichia coli O157 : H7 and its association with PmrC.. Microbiology 152: 657-666 [Abstract] [Full Text]  
  • Froelich, J. M., Tran, K., Wall, D. (2006). A pmrA Constitutive Mutant Sensitizes Escherichia coli to Deoxycholic Acid. J. Bacteriol. 188: 1180-1183 [Abstract] [Full Text]  
  • Merighi, M., Carroll-Portillo, A., Septer, A. N., Bhatiya, A., Gunn, J. S. (2006). Role of Salmonella enterica Serovar Typhimurium Two-Component System PreA/PreB in Modulating PmrA-Regulated Gene Transcription. J. Bacteriol. 188: 141-149 [Abstract] [Full Text]  
  • Porwollik, S., Santiviago, C. A., Cheng, P., Florea, L., McClelland, M. (2005). Differences in Gene Content between Salmonella enterica Serovar Enteritidis Isolates and Comparison to Closely Related Serovars Gallinarum and Dublin. J. Bacteriol. 187: 6545-6555 [Abstract] [Full Text]  
  • Tzeng, Y.-L., Ambrose, K. D., Zughaier, S., Zhou, X., Miller, Y. K., Shafer, W. M., Stephens, D. S. (2005). Cationic Antimicrobial Peptide Resistance in Neisseria meningitidis. J. Bacteriol. 187: 5387-5396 [Abstract] [Full Text]  
  • Winfield, M. D., Groisman, E. A. (2004). Phenotypic differences between Salmonella and Escherichia coli resulting from the disparate regulation of homologous genes. Proc. Natl. Acad. Sci. USA 101: 17162-17167 [Abstract] [Full Text]  
  • Maier, R. J., Olczak, A., Maier, S., Soni, S., Gunn, J. (2004). Respiratory Hydrogen Use by Salmonella enterica Serovar Typhimurium Is Essential for Virulence. Infect. Immun. 72: 6294-6299 [Abstract] [Full Text]  
  • Tzeng, Y.-L., Datta, A., Ambrose, K., Lo, M., Davies, J. K., Carlson, R. W., Stephens, D. S., Kahler, C. M. (2004). The MisR/MisS Two-component Regulatory System Influences Inner Core Structure and Immunotype of Lipooligosaccharide in Neisseria meningitidis. J. Biol. Chem. 279: 35053-35062 [Abstract] [Full Text]  
  • Codling, C. E., Jones, B. V., Mahenthiralingam, E., Russell, A. D., Maillard, J.-Y. (2004). Identification of genes involved in the susceptibility of Serratia marcescens to polyquaternium-1. J Antimicrob Chemother 54: 370-375 [Abstract] [Full Text]  
  • Cao, M., Helmann, J. D. (2004). The Bacillus subtilis Extracytoplasmic-Function {sigma}X Factor Regulates Modification of the Cell Envelope and Resistance to Cationic Antimicrobial Peptides. J. Bacteriol. 186: 1136-1146 [Abstract] [Full Text]  
  • Kim, W., Killam, T., Sood, V., Surette, M. G. (2003). Swarm-Cell Differentiation in Salmonellaenterica Serovar Typhimurium Results in Elevated Resistance to Multiple Antibiotics. J. Bacteriol. 185: 3111-3117 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»