This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rabsch, W. Articles by Williams, P. H. Search for Related Content PubMed PubMed Citation Articles by Rabsch, W. Articles by Williams, P. H.

 Previous Article  |  Next Article 

Infection and Immunity, December 2003, p. 6953-6961, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6953-6961.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of Receptor Proteins for Enterobactin and 2,3-Dihydroxybenzoylserine in Virulence of Salmonella enterica

Robert Koch-Institut, Wernigerode,¹ Bundesforschungsanstalt für Viruskrankheiten der Tiere, Jena, Germany,² Department of Microbiology and Immunology, University of Leicester, Leicester, United Kingdom³

Received 10 March 2003/ Returned for modification 15 April 2003/ Accepted 11 September 2003

Single, double, and triple mutants of an enterobactin-deficient mutant strain of Salmonella enterica serovar Typhimurium were constructed that were defective in the expression of the iron-regulated outer membrane proteins (IROMPs) FepA, IroN, and Cir, which are proposed to function as catecholate receptors. Uptake of naturally occurring and chemically synthesized catecholate molecules by these mutants was assessed in standard growth promotion assays. Unique patterns of uptake were identified for each IROMP; specifically, FepA and IroN were confirmed to be required for transport of enterobactin, and all three proteins were shown to function as receptors for the enterobactin breakdown product 2,3-dihydroxybenzoylserine. The fepA, iroN, and cir alleles were transduced to enterobactin-proficient strains of S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, and the resulting phenotypes were confirmed by analysis of outer membrane protein profiles, by sensitivity to KP-736, a catecholate-cephalosporin conjugate, and by growth promotion tests on egg white agar. Intragastric infections of mice with the S. enterica serovar Typhimurium strains indicated that the parental strain and the fepA iroN double mutant were similarly virulent but that the fepA iroN cir triple mutant was significantly attenuated. Moreover, in mixed infections, the fepA iroN mutant showed similar cecal colonization and invasion of the liver to the parental strain, while the triple mutant showed significantly reduced cecal colonization and no measurable spread to the liver. Infections of 4-day-old chicks with S. enterica serovar Enteritidis strains also indicated that mutation of the fepA iroN genes did not significantly reduce cecal colonization and systemic spread compared with those of the parental strain. The results indicate that, while enterobactin uptake is not essential for the virulence of S. enterica serovars in mouse and chicken infection models, the ability to take up 2,3-dihydroxybenzoylserine via any of the three catecholate siderophore receptors appears to play an important role, since the S. enterica serovar Typhimurium triple mutant was significantly attenuated in the mouse model. Salmochelins appear not to be involved in the virulence of S. enterica.

Editor: F. C. Fang

This article has been cited by other articles:

• Caza, M., Lepine, F., Milot, S., Dozois, C. M. (2008). Specific Roles of the iroBCDEN Genes in Virulence of an Avian Pathogenic Escherichia coli O78 Strain and in Production of Salmochelins. Infect. Immun. 76: 3539-3549 [Abstract] [Full Text]  
• Milne, T. S., Michell, S. L., Diaper, H., Wikstrom, P., Svensson, K., Oyston, P. C. F., Titball, R. W. (2007). A 55 kDa hypothetical membrane protein is an iron-regulated virulence factor of Francisella tularensis subsp. novicida U112. J Med Microbiol 56: 1268-1276 [Abstract] [Full Text]  
• Rabsch, W., Ma, L., Wiley, G., Najar, F. Z., Kaserer, W., Schuerch, D. W., Klebba, J. E., Roe, B. A., Gomez, J. A. L., Schallmey, M., Newton, S. M. C., Klebba, P. E. (2007). FepA- and TonB-Dependent Bacteriophage H8: Receptor Binding and Genomic Sequence. J. Bacteriol. 189: 5658-5674 [Abstract] [Full Text]  
• Balado, M., Osorio, C. R., Lemos, M. L. (2006). A gene cluster involved in the biosynthesis of vanchrobactin, a chromosome-encoded siderophore produced by Vibrio anguillarum. Microbiology 152: 3517-3528 [Abstract] [Full Text]  
• Leveille, S., Caza, M., Johnson, J. R., Clabots, C., Sabri, M., Dozois, C. M. (2006). Iha from an Escherichia coli Urinary Tract Infection Outbreak Clonal Group A Strain Is Expressed In Vivo in the Mouse Urinary Tract and Functions as a Catecholate Siderophore Receptor.. Infect. Immun. 74: 3427-3436 [Abstract] [Full Text]  
• Speziali, C. D., Dale, S. E., Henderson, J. A., Vines, E. D., Heinrichs, D. E. (2006). Requirement of Staphylococcus aureus ATP-Binding Cassette-ATPase FhuC for Iron-Restricted Growth and Evidence that It Functions with More than One Iron Transporter. J. Bacteriol. 188: 2048-2055 [Abstract] [Full Text]  
• Palyada, K., Threadgill, D., Stintzi, A. (2004). Iron Acquisition and Regulation in Campylobacter jejuni. J. Bacteriol. 186: 4714-4729 [Abstract] [Full Text]