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 Gunn, J. S.
Right arrow Articles by Miller, S. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gunn, J. S.
Right arrow Articles by Miller, S. I.

 Previous Article  |  Next Article 

Infection and Immunity, November 2000, p. 6139-6146, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Genetic and Functional Analysis of a PmrA-PmrB-Regulated Locus Necessary for Lipopolysaccharide Modification, Antimicrobial Peptide Resistance, and Oral Virulence of Salmonella enterica Serovar Typhimurium

John S. Gunn,1,* Sara S. Ryan,1 Jennifer C. Van Velkinburgh,1 Robert K. Ernst,2 and Samuel I. Miller2

Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229,1 and Departments of Medicine and Microbiology, University of Washington, Seattle, Washington 981952

Received 8 June 2000/Returned for modification 28 July 2000/Accepted 4 August 2000

The two-component regulatory system PmrA-PmrB confers resistance of Salmonella spp. to cationic antimicrobial peptides (AP) such as polymyxin (PM), bactericidal/permeability-increasing protein, and azurocidin. This resistance occurs by transcriptional activation of two loci termed pmrE and pmrHFIJKLM. Both pmrE and pmrHFIJKLM produce products required for the biosynthesis of lipid A with 4-aminoarabinose (Ara4N). Ara4N addition creates a more positively charged lipopolysaccharide (LPS) and thus reduces cationic AP binding. Experiments were conducted to further analyze the regulation of the pmrHFIJKLM operon and the role of this operon and the surrounding genomic region in LPS modification and antimicrobial peptide resistance. The pmrHFIJKLM genes are cotranscribed and over 3,000-fold regulated by PmrA-PmrB. The pmrHFIJKLM promoter bound PmrA, as determined by gel shift analysis, as did a 40-bp region of the PmrA-PmrB-regulated pmrCAB promoter. Construction of nonpolar mutations in the pmrHFIJKLM genes showed that all except pmrM were necessary for the Ara4N addition to lipid A and PM resistance. The flanking genes of the operon (pmrG and pmrD) were not necessary for PM resistance, but pmrD was shown to be regulated by the PhoP-PhoQ regulatory system. BALB/c mice inoculated with pmrA and pmrHFIJKLM mutant strains demonstrated virulence attenuation when the strains were administered orally but not when they were administered intraperitoneally, indicating that Ara4N addition may be important for resistance to host innate defenses within intestinal tissues.

* Corresponding author. Mailing address: University of Texas Health Science Center at San Antonio, Department of Microbiology, MC 7758, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. Phone: (210) 567-3973. Fax: (210) 567-3795. E-mail: gunnj{at}uthscsa.edu.

Infection and Immunity, November 2000, p. 6139-6146, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Pilonieta, M. C., Erickson, K. D., Ernst, R. K., Detweiler, C. S. (2009). A Protein Important for Antimicrobial Peptide Resistance, YdeI/OmdA, Is in the Periplasm and Interacts with OmpD/NmpC. J. Bacteriol. 191: 7243-7252 [Abstract] [Full Text]  
  • Abi Khattar, Z., Rejasse, A., Destoumieux-Garzon, D., Escoubas, J. M., Sanchis, V., Lereclus, D., Givaudan, A., Kallassy, M., Nielsen-Leroux, C., Gaudriault, S. (2009). The dlt Operon of Bacillus cereus Is Required for Resistance to Cationic Antimicrobial Peptides and for Virulence in Insects. J. Bacteriol. 191: 7063-7073 [Abstract] [Full Text]  
  • Adams, M. D., Nickel, G. C., Bajaksouzian, S., Lavender, H., Murthy, A. R., Jacobs, M. R., Bonomo, R. A. (2009). Resistance to Colistin in Acinetobacter baumannii Associated with Mutations in the PmrAB Two-Component System. Antimicrob. Agents Chemother. 53: 3628-3634 [Abstract] [Full Text]  
  • Arafah, S., Rosso, M.-L., Rehaume, L., Hancock, R. E. W., Simonet, M., Marceau, M. (2009). An iron-regulated LysR-type element mediates antimicrobial peptide resistance and virulence in Yersinia pseudotuberculosis. Microbiology 155: 2168-2181 [Abstract] [Full Text]  
  • Sun, S., Negrea, A., Rhen, M., Andersson, D. I. (2009). Genetic Analysis of Colistin Resistance in Salmonella enterica Serovar Typhimurium. Antimicrob. Agents Chemother. 53: 2298-2305 [Abstract] [Full Text]  
  • Gooderham, W. J., Gellatly, S. L., Sanschagrin, F., McPhee, J. B., Bains, M., Cosseau, C., Levesque, R. C., Hancock, R. E. W. (2009). The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa. Microbiology 155: 699-711 [Abstract] [Full Text]  
  • Manabe, T., Kawasaki, K. (2008). Extracellular Loops of Lipid A 3-O-Deacylase PagL Are Involved in Recognition of Aminoarabinose-Based Membrane Modifications in Salmonella enterica Serovar Typhimurium. J. Bacteriol. 190: 5597-5606 [Abstract] [Full Text]  
  • Pranting, M., Negrea, A., Rhen, M., Andersson, D. I. (2008). Mechanism and Fitness Costs of PR-39 Resistance in Salmonella enterica Serovar Typhimurium LT2. Antimicrob. Agents Chemother. 52: 2734-2741 [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]  
  • Eswarappa, S. M., Panguluri, K. K., Hensel, M., Chakravortty, D. (2008). The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence. Microbiology 154: 666-678 [Abstract] [Full Text]  
  • Yan, A., Guan, Z., Raetz, C. R. H. (2007). An Undecaprenyl Phosphate-Aminoarabinose Flippase Required for Polymyxin Resistance in Escherichia coli. J. Biol. Chem. 282: 36077-36089 [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]  
  • Mohapatra, N. P., Soni, S., Bell, B. L., Warren, R., Ernst, R. K., Muszynski, A., Carlson, R. W., Gunn, J. S. (2007). Identification of an Orphan Response Regulator Required for the Virulence of Francisella spp. and Transcription of Pathogenicity Island Genes. Infect. Immun. 75: 3305-3314 [Abstract] [Full Text]  
  • Kawasaki, K., China, K., Nishijima, M. (2007). Release of the Lipopolysaccharide Deacylase PagL from Latency Compensates for a Lack of Lipopolysaccharide Aminoarabinose Modification-Dependent Resistance to the Antimicrobial Peptide Polymyxin B in Salmonella enterica. J. Bacteriol. 189: 4911-4919 [Abstract] [Full Text]  
  • Mascher, T., Helmann, J. D., Unden, G. (2006). Stimulus Perception in Bacterial Signal-Transducing Histidine Kinases. Microbiol. Mol. Biol. Rev. 70: 910-938 [Abstract] [Full Text]  
  • Reynolds, C. M., Ribeiro, A. A., McGrath, S. C., Cotter, R. J., Raetz, C. R. H., Trent, M. S. (2006). An Outer Membrane Enzyme Encoded by Salmonella typhimurium lpxR That Removes the 3'-Acyloxyacyl Moiety of Lipid A. J. Biol. Chem. 281: 21974-21987 [Abstract] [Full Text]  
  • Trent, M. S., Stead, C. M., Tran, A. X., Hankins, J. V. (2006). Invited review: Diversity of endotoxin and its impact on pathogenesis. Innate Immunity 12: 205-223 [Abstract]  
  • Campos, M. A., Morey, P., Bengoechea, J. A. (2006). Quinolones sensitize gram-negative bacteria to antimicrobial peptides.. Antimicrob. Agents Chemother. 50: 2361-2367 [Abstract] [Full Text]  
  • Tran, A. X., Whittimore, J. D., Wyrick, P. B., McGrath, S. C., Cotter, R. J., Trent, M. S. (2006). The Lipid A 1-Phosphatase of Helicobacter pylori Is Required for Resistance to the Antimicrobial Peptide Polymyxin.. J. Bacteriol. 188: 4531-4541 [Abstract] [Full Text]  
  • Cole, A. L., Yang, O. O., Warren, A. D., Waring, A. J., Lehrer, R. I., Cole, A. M. (2006). HIV-1 Adapts to a Retrocyclin with Cationic Amino Acid Substitutions That Reduce Fusion Efficiency of gp41.. J. Immunol. 176: 6900-6905 [Abstract] [Full Text]  
  • Faucher, Séb. P., Porwollik, S., Dozois, C. M., McClelland, M., Daigle, F. (2006). Transcriptome of Salmonella enterica serovar Typhi within macrophages revealed through the selective capture of transcribed sequences. Proc. Natl. Acad. Sci. USA 103: 1906-1911 [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]  
  • Merighi, M., Ellermeier, C. D., Slauch, J. M., Gunn, J. S. (2005). Resolvase-In Vivo Expression Technology Analysis of the Salmonella enterica Serovar Typhimurium PhoP and PmrA Regulons in BALB/c Mice. J. Bacteriol. 187: 7407-7416 [Abstract] [Full Text]  
  • Kristian, S. A., Datta, V., Weidenmaier, C., Kansal, R., Fedtke, I., Peschel, A., Gallo, R. L., Nizet, V. (2005). D-Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion. J. Bacteriol. 187: 6719-6725 [Abstract] [Full Text]  
  • Kim, W., Surette, M. G. (2005). Prevalence of Surface Swarming Behavior in Salmonella. J. Bacteriol. 187: 6580-6583 [Abstract] [Full Text]  
  • Tran, A. X., Lester, M. E., Stead, C. M., Raetz, C. R. H., Maskell, D. J., McGrath, S. C., Cotter, R. J., Trent, M. S. (2005). Resistance to the Antimicrobial Peptide Polymyxin Requires Myristoylation of Escherichia coli and Salmonella typhimurium Lipid A. J. Biol. Chem. 280: 28186-28194 [Abstract] [Full Text]  
  • Williams, G. J., Breazeale, S. D., Raetz, C. R. H., Naismith, J. H. (2005). Structure and Function of Both Domains of ArnA, a Dual Function Decarboxylase and a Formyltransferase, Involved in 4-Amino-4-deoxy-L-arabinose Biosynthesis. J. Biol. Chem. 280: 23000-23008 [Abstract] [Full Text]  
  • Rediers, H., Rainey, P. B., Vanderleyden, J., De Mot, R. (2005). Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression. Microbiol. Mol. Biol. Rev. 69: 217-261 [Abstract] [Full Text]  
  • Tamayo, R., Choudhury, B., Septer, A., Merighi, M., Carlson, R., Gunn, J. S. (2005). Identification of cptA, a PmrA-Regulated Locus Required for Phosphoethanolamine Modification of the Salmonella enterica Serovar Typhimurium Lipopolysaccharide Core. J. Bacteriol. 187: 3391-3399 [Abstract] [Full Text]  
  • Zhang, H., Morikawa, K., Ohta, T., Kato, Y. (2005). In vitro resistance to the CS{alpha}{beta}-type antimicrobial peptide ASABF- is conferred by overexpression of sigma factor sigB in Staphylococcus aureus. J Antimicrob Chemother 55: 686-691 [Abstract] [Full Text]  
  • Winfield, M. D., Latifi, T., Groisman, E. A. (2005). Transcriptional Regulation of the 4-Amino-4-deoxy-L-arabinose Biosynthetic Genes in Yersinia pestis. J. Biol. Chem. 280: 14765-14772 [Abstract] [Full Text]  
  • Breazeale, S. D., Ribeiro, A. A., McClerren, A. L., Raetz, C. R. H. (2005). A Formyltransferase Required for Polymyxin Resistance in Escherichia coli and the Modification of Lipid A with 4-Amino-4-deoxy-L-arabinose: IDENTIFICATION AND FUNCTION OF UDP-4-DEOXY-4-FORMAMIDO-L-ARABINOSE. J. Biol. Chem. 280: 14154-14167 [Abstract] [Full Text]  
  • Tanabe, H., Ayabe, T., Bainbridge, B., Guina, T., Ernst, R. K., Darveau, R. P., Miller, S. I., Ouellette, A. J. (2005). Mouse Paneth Cell Secretory Responses to Cell Surface Glycolipids of Virulent and Attenuated Pathogenic Bacteria. Infect. Immun. 73: 2312-2320 [Abstract] [Full Text]  
  • Kawasaki, K., Ernst, R. K., Miller, S. I. (2005). Inhibition of Salmonella enterica Serovar Typhimurium Lipopolysaccharide Deacylation by Aminoarabinose Membrane Modification. J. Bacteriol. 187: 2448-2457 [Abstract] [Full Text]  
  • Sahl, H.-G., Pag, U., Bonness, S., Wagner, S., Antcheva, N., Tossi, A. (2005). Mammalian defensins: structures and mechanism of antibiotic activity. J. Leukoc. Biol. 77: 466-475 [Abstract] [Full Text]  
  • Geurtsen, J., Steeghs, L., Hove, J. t., van der Ley, P., Tommassen, J. (2005). Dissemination of Lipid A Deacylases (PagL) among Gram-negative Bacteria: IDENTIFICATION OF ACTIVE-SITE HISTIDINE AND SERINE RESIDUES. J. Biol. Chem. 280: 8248-8259 [Abstract] [Full Text]  
  • Bennett, H. P. J., Clarke, D. J. (2005). The pbgPE operon in Photorhabdus luminescens Is Required for Pathogenicity and Symbiosis. J. Bacteriol. 187: 77-84 [Abstract] [Full Text]  
  • Shelburne, C. E., Coulter, W. A., Olguin, D., Lantz, M. S., Lopatin, D. E. (2005). Induction of {beta}-Defensin Resistance in the Oral Anaerobe Porphyromonas gingivalis. Antimicrob. Agents Chemother. 49: 183-187 [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]  
  • Campos, M. A., Vargas, M. A., Regueiro, V., Llompart, C. M., Alberti, S., Bengoechea, J. A. (2004). Capsule Polysaccharide Mediates Bacterial Resistance to Antimicrobial Peptides. Infect. Immun. 72: 7107-7114 [Abstract] [Full Text]  
  • Marceau, M., Sebbane, F., Ewann, F., Collyn, F., Lindner, B., Campos, M. A., Bengoechea, J.-A., Simonet, M. (2004). The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is not required for virulence. Microbiology 150: 3947-3957 [Abstract] [Full Text]  
  • Matsukawa, M., Greenberg, E. P. (2004). Putative Exopolysaccharide Synthesis Genes Influence Pseudomonas aeruginosa Biofilm Development. J. Bacteriol. 186: 4449-4456 [Abstract] [Full Text]  
  • Lee, H., Hsu, F.-F., Turk, J., Groisman, E. A. (2004). The PmrA-Regulated pmrC Gene Mediates Phosphoethanolamine Modification of Lipid A and Polymyxin Resistance in Salmonella enterica. J. Bacteriol. 186: 4124-4133 [Abstract] [Full Text]  
  • Baud, D., Benyacoub, J., Revaz, V., Kok, M., Ponci, F., Bobst, M., Curtiss, R. III, De Grandi, P., Nardelli-Haefliger, D. (2004). Immunogenicity against Human Papillomavirus Type 16 Virus-Like Particles Is Strongly Enhanced by the PhoPc Phenotype in Salmonella enterica Serovar Typhimurium. Infect. Immun. 72: 750-756 [Abstract] [Full Text]  
  • Moskowitz, S. M., Ernst, R. K., Miller, S. I. (2004). PmrAB, a Two-Component Regulatory System of Pseudomonas aeruginosa That Modulates Resistance to Cationic Antimicrobial Peptides and Addition of Aminoarabinose to Lipid A. J. Bacteriol. 186: 575-579 [Abstract] [Full Text]  
  • Swords, W. E., Jones, P. A., Apicella, M. A. (2003). Review: The lipo-oligosaccharides of Haemophilus influenzae: an interesting array of characters. Innate Immunity 9: 131-144 [Abstract]  
  • 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]  
  • Kato, A., Latifi, T., Groisman, E. A. (2003). Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD. Proc. Natl. Acad. Sci. USA 100: 4706-4711 [Abstract] [Full Text]  
  • Tamayo, R., Ryan, S. S., McCoy, A. J., Gunn, J. S. (2002). Identification and Genetic Characterization of PmrA-Regulated Genes and Genes Involved in Polymyxin B Resistance in Salmonella enterica Serovar Typhimurium. Infect. Immun. 70: 6770-6778 [Abstract] [Full Text]  
  • Tucker, D. L., Tucker, N., Conway, T. (2002). Gene Expression Profiling of the pH Response in Escherichia coli. J. Bacteriol. 184: 6551-6558 [Abstract] [Full Text]  
  • Ulvatne, H., Haukland, H. H., Samuelsen, O., Kramer, M., Vorland, L. H. (2002). Proteases in Escherichia coli and Staphylococcus aureus confer reduced susceptibility to lactoferricin B. J Antimicrob Chemother 50: 461-467 [Abstract] [Full Text]  
  • Swords, W. E., Chance, D. L., Cohn, L. A., Shao, J., Apicella, M. A., Smith, A. L. (2002). Acylation of the Lipooligosaccharide of Haemophilus influenzae and Colonization: an htrB Mutation Diminishes the Colonization of Human Airway Epithelial Cells. Infect. Immun. 70: 4661-4668 [Abstract] [Full Text]  
  • Brodsky, I. E., Ernst, R. K., Miller, S. I., Falkow, S. (2002). mig-14 Is a Salmonella Gene That Plays a Role in Bacterial Resistance to Antimicrobial Peptides. J. Bacteriol. 184: 3203-3213 [Abstract] [Full Text]  
  • Zhou, Z., Ribeiro, A. A., Lin, S., Cotter, R. J., Miller, S. I., Raetz, C. R. H. (2001). Lipid A Modifications in Polymyxin-resistant Salmonella typhimurium. PMRA-DEPENDENT 4-AMINO-4-DEOXY-L-ARABINOSE, AND PHOSPHOETHANOLAMINE INCORPORATION. J. Biol. Chem. 276: 43111-43121 [Abstract] [Full Text]  
  • Trent, M. S., Ribeiro, A. A., Lin, S., Cotter, R. J., Raetz, C. R. H. (2001). An Inner Membrane Enzyme in Salmonella and Escherichia coli That Transfers 4-Amino-4-deoxy-L-arabinose to Lipid A. INDUCTION IN POLYMYXIN-RESISTANT MUTANTS AND ROLE OF A NOVEL LIPID-LINKED DONOR. J. Biol. Chem. 276: 43122-43131 [Abstract] [Full Text]  
  • Trent, M. S., Ribeiro, A. A., Doerrler, W. T., Lin, S., Cotter, R. J., Raetz, C. R. H. (2001). Accumulation of a Polyisoprene-linked Amino Sugar in Polymyxin-resistant Salmonella typhimurium and Escherichia coli. STRUCTURAL CHARACTERIZATION AND TRANSFER TO LIPID A IN THE PERIPLASM. J. Biol. Chem. 276: 43132-43144 [Abstract] [Full Text]  
  • Breazeale, S. D., Ribeiro, A. A., Raetz, C. R. H. (2002). Oxidative Decarboxylation of UDP-Glucuronic Acid in Extracts of Polymyxin-resistant Escherichia coli. ORIGIN OF LIPID A SPECIES MODIFIED WITH 4-AMINO-4-DEOXY-L-ARABINOSE. J. Biol. Chem. 277: 2886-2896 [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»