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Infection and Immunity, July 2009, p. 2741-2753, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00006-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prolonged Impact of Antibiotics on Intestinal Microbial Ecology and Susceptibility to Enteric Salmonella Infection

Amy Croswell,¹ Elad Amir,¹ Paul Teggatz,¹ Melissa Barman,¹ and Nita H. Salzman^1,2*

Department of Pediatrics, Division of Gastroenterology,¹ Department of Microbiology and Molecular Genetics, the Medical College of Wisconsin, Milwaukee, Wisconsin²

Received 2 January 2009/ Returned for modification 6 February 2009/ Accepted 15 April 2009

The impact of antibiotics on the host's protective microbiota and the resulting increased susceptibility to mucosal infection are poorly understood. In this study, antibiotic regimens commonly applied to murine enteritis models are used to examine the impact of antibiotics on the intestinal microbiota, the time course of recovery of the biota, and the resulting susceptibility to enteric Salmonella infection. Molecular analysis of the microbiota showed that antibiotic treatment has an impact on the colonization of the murine gut that is site and antibiotic dependent. While combinations of antibiotics were able to eliminate culturable bacteria, none of the antibiotic treatments were effective at sterilizing the intestinal tract. Recovery of total bacterial numbers occurs within 1 week after antibiotic withdrawal, but alterations in specific bacterial groups persist for several weeks. Increased Salmonella translocation associated with antibiotic pretreatment corrects rapidly in association with the recovery of the most dominant bacterial group, which parallels the recovery of total bacterial numbers. However, susceptibility to intestinal colonization and mucosal inflammation persists when mice are infected several weeks after withdrawal of antibiotics, correlating with subtle alterations in the intestinal microbiome involving alterations of specific bacterial groups. These results show that the colonizing microbiotas are integral to mucosal host protection, that specific features of the microbiome impact different aspects of enteric Salmonella pathogenesis, and that antibiotics can have prolonged deleterious effects on intestinal colonization resistance.

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* Corresponding author. Mailing address: Department of Pediatrics, Division of Gastroenterology, the Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Phone: (414) 456-4244. Fax: (414) 266-3676. E-mail: nsalzman{at}mcw.edu

Published ahead of print on 20 April 2009.

Editor: B. A. McCormick

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Infection and Immunity, July 2009, p. 2741-2753, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00006-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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