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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,
Jack S.
Ikeda,1,
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.

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

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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