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 McCoy, A. J.
Right arrow Articles by Gunn, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCoy, A. J.
Right arrow Articles by Gunn, J. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2001, p. 2030-2037, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2030-2037.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Proteus mirabilis Mutants with Increased Sensitivity to Antimicrobial Peptides

Andrea J. McCoy,1 Hongjian Liu,2 Timothy J. Falla,2 and John S. Gunn1,*

Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900,1 and IntraBiotics Pharmaceuticals, Inc., Mountain View, California 940432

Received 20 September 2000/Returned for modification 29 January 2001/Accepted 21 April 2001

Antimicrobial peptides (APs) are important components of the innate defenses of animals, plants, and microorganisms. However, some bacterial pathogens are resistant to the action of APs. For example, Proteus mirabilis is highly resistant to the action of APs, such as polymyxin B (PM), protegrin, and the synthetic protegrin analog IB-367. To better understand this resistance, a transposon mutagenesis approach was used to generate P. mirabilis mutants sensitive to APs. Four unique PM-sensitive mutants of P. mirabilis were identified (these mutants were >2 to >128 times more sensitive than the wild type). Two of these mutants were also sensitive to IB-367 (16 and 128 times more sensitive than the wild type). Lipopolysaccharide (LPS) profiles of the PM- and protegrin-sensitive mutants demonstrated marked differences in both the lipid A and O-antigen regions, while the PM-sensitive mutants appeared to have alterations of either lipid A or O antigen. Matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis of the wild-type and PM-sensitive mutant lipid A showed species with one or two aminoarabinose groups, while lipid A from the PM- and protegrin-sensitive mutants was devoid of aminoarabinose. When the mutants were streaked on an agar-containing medium, the swarming motility of the PM- and protegrin-sensitive mutants was completely inhibited and the swarming motility of the mutants sensitive to only PM was markedly decreased. DNA sequence analysis of the mutagenized loci revealed similarities to an O-acetyltransferase (PM and protegrin sensitive) and ATP synthase and sap loci (PM sensitive). These data further support the role of LPS modifications as an elaborate mechanism in the resistance of certain bacterial species to APs and suggest that LPS surface charge alterations may play a role in P. mirabilis swarming motility.

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

Antimicrobial Agents and Chemotherapy, July 2001, p. 2030-2037, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2030-2037.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Gooderham, W. J., Bains, M., McPhee, J. B., Wiegand, I., Hancock, R. E. W. (2008). Induction by Cationic Antimicrobial Peptides and Involvement in Intrinsic Polymyxin and Antimicrobial Peptide Resistance, Biofilm Formation, and Swarming Motility of PsrA in Pseudomonas aeruginosa. J. Bacteriol. 190: 5624-5634 [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]  
  • Jacobsen, S. M., Stickler, D. J., Mobley, H. L. T., Shirtliff, M. E. (2008). Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis. Clin. Microbiol. Rev. 21: 26-59 [Abstract] [Full Text]  
  • Pamp, S. J., Tolker-Nielsen, T. (2007). Multiple Roles of Biosurfactants in Structural Biofilm Development by Pseudomonas aeruginosa. J. Bacteriol. 189: 2531-2539 [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]  
  • 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]  
  • Clavijo, R. I., Loui, C., Andersen, G. L., Riley, L. W., Lu, S. (2006). Identification of Genes Associated with Survival of Salmonella enterica Serovar Enteritidis in Chicken Egg Albumen. Appl. Environ. Microbiol. 72: 1055-1064 [Abstract] [Full Text]  
  • Soo, P.-C., Wei, J.-R., Horng, Y.-T., Hsieh, S.-C., Ho, S.-W., Lai, H.-C. (2005). Characterization of the dapA-nlpB Genetic Locus Involved in Regulation of Swarming Motility, Cell Envelope Architecture, Hemolysin Production, and Cell Attachment Ability in Serratia marcescens. Infect. Immun. 73: 6075-6084 [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]  
  • Mason, K. M., Munson, R. S. Jr., Bakaletz, L. O. (2005). A Mutation in the sap Operon Attenuates Survival of Nontypeable Haemophilus influenzae in a Chinchilla Model of Otitis Media. Infect. Immun. 73: 599-608 [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]  
  • Belas, R., Manos, J., Suvanasuthi, R. (2004). Proteus mirabilis ZapA Metalloprotease Degrades a Broad Spectrum of Substrates, Including Antimicrobial Peptides. Infect. Immun. 72: 5159-5167 [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]  
  • Yeaman, M. R., Yount, N. Y. (2003). Mechanisms of Antimicrobial Peptide Action and Resistance. Pharmacol. Rev. 55: 27-55 [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]  
  • Starner, T. D., Swords, W. E., Apicella, M. A., McCray, P. B. Jr. (2002). Susceptibility of Nontypeable Haemophilus influenzae to Human {beta}-Defensins Is Influenced by Lipooligosaccharide Acylation. Infect. Immun. 70: 5287-5289 [Abstract] [Full Text]  
  • Sitaram, N., Sai, K. P., Singh, S., Sankaran, K., Nagaraj, R. (2002). Structure-Function Relationship Studies on the Frog Skin Antimicrobial Peptide Tigerinin 1: Design of Analogs with Improved Activity and Their Action on Clinical Bacterial Isolates. Antimicrob. Agents Chemother. 46: 2279-2283 [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]  


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