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Infection and Immunity, September 2001, p. 5619-5625, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5619-5625.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Absence of All Components of the Flagellar Export and Synthesis Machinery Differentially Alters Virulence of Salmonella enterica Serovar Typhimurium in Models of Typhoid Fever, Survival in Macrophages, Tissue Culture Invasiveness, and Calf Enterocolitis

Clare K. Schmitt,1,dagger Jack S. Ikeda,1,Dagger Stephen C. Darnell,1 Patricia R. Watson,2 Jennifer Bispham,2 Timothy S. Wallis,2 Debra L. Weinstein,1 Eleanor S. Metcalf,1 and Alison D. O'Brien1,*

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine, Bethesda, Maryland 20814,1 and Institute for Animal Health, Compton, Newbury, Berkshire, United Kingdom RG20 7NN2

Received 21 March 2001/Returned for modification 3 May 2001/Accepted 13 June 2001

In this study, we constructed an flhD (the master flagellar regulator gene) mutant of Salmonella enterica serovar Typhimurium and compared the virulence of the strain to that of the wild-type strain in a series of assays that included the mouse model of typhoid fever, the mouse macrophage survival assay, an intestinal epithelial cell adherence and invasion assay, and the calf model of enterocolitis. We found that the flhD mutant was more virulent than its parent in the mouse and displayed slightly faster net growth between 4 and 24 h of infection in mouse macrophages. Conversely, the flhD mutant exhibited diminished invasiveness for human and mouse intestinal epithelial cells, as well as a reduced capacity to induce fluid secretion and evoke a polymorphonuclear leukocyte response in the calf ligated-loop assay. These findings, taken with the results from virulence assessment assays done on an fljB fliC mutant of serovar Typhimurium that does not produce flagellin but does synthesize the flagellar secretory apparatus, indicate that neither the presence of flagella (as previously reported) nor the synthesis of the flagellar export machinery are necessary for pathogenicity of the organism in the mouse. Conversely, the presence of flagella is required for the full invasive potential of the bacterium in tissue culture and for the influx of polymorphonuclear leukocytes in the calf intestine, while the flagellar secretory components are also necessary for the induction of maximum fluid secretion in that enterocolitis model. A corollary to this conclusion is that, as has previously been surmised but not demonstrated in a comparative investigation of the same mutant strains, the mouse systemic infection and macrophage assays measure aspects of virulence different from those of the tissue culture invasion assay, and the latter is more predictive of findings in the calf enterocolitis model.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine, 4301 Jones Bridge Rd., Bethesda, MD 20814. Phone: (301) 295-3419. Fax: (301) 295-3773. E-mail: aobrien{at}usuhs.mil.

dagger Present address: National Institutes of Health, Center for Scientific Review, Bethesda, MD 20892.

Dagger Present address: Department of Animal Sciences, Colorado State University, Fort Collins, CO 80523.

Infection and Immunity, September 2001, p. 5619-5625, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5619-5625.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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