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Infection and Immunity, June 2003, p. 3392-3401, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3392-3401.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Contribution of Proton-Translocating Proteins to the Virulence of Salmonella enterica Serovars Typhimurium, Gallinarum, and Dublin in Chickens and Mice

A. K. Turner,{dagger} L. Z. Barber,{ddagger} P. Wigley, S. Muhammad, M. A. Jones, M. A. Lovell, S. Hulme, and P. A. Barrow*

Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, United Kingdom

Received 4 December 2002/ Returned for modification 29 January 2003/ Accepted 18 March 2003

We investigated the attenuating effects of a range of respiratory chain mutations in three Salmonella serovars which might be used in the development of live vaccines. We tested mutations in nuoG, cydA, cyoA, atpB, and atpH in three serovars of Salmonella enterica: Typhimurium, Dublin, and Gallinarum. All three serovars were assessed for attenuation in their relevant virulence assays of typhoid-like infections. Serovar Typhimurium was assessed in 1-day-old chickens and the mouse. Serovar Gallinarum 9 was assessed in 3-week-old chickens, and serovar Dublin was assessed in 6-week-old mice. Our data show variation in attenuation for the nuoG, cydA, and cyoA mutations within the different serovar-host combinations. However, mutations in atpB and atpH were highly attenuating for all three serovars in the various virulence assays. Further investigation of the mutations in the atp operon showed that the bacteria were less invasive in vivo, showing reduced in vitro survival within phagocytic cells and reduced acid tolerance. We present data showing that this reduced acid tolerance is due to an inability to adapt to conditions rather than a general sensitivity to reduced pH. The data support the targeting of respiratory components for the production of live vaccines and suggest that mutations in the atp operon provide suitable candidates for broad-spectrum attenuation of a range of Salmonella serovars.

* Corresponding author. Mailing address: Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, United Kingdom. Phone: 44-1635-578411. Fax: 44-1635-577243. E-mail: paul.barrow{at}bbsrc.ac.uk.

Editor: A. D. O'Brien

{dagger} Present address: Acambis Research Ltd., Peterhouse Technology Park, Cambridge CB1 9PT, United Kingdom.

{ddagger} Present address: Institute of Infection and Immunity, Queen's Medical Centre, Nottingham University, Nottingham NG7 2UH, United Kingdom.

Infection and Immunity, June 2003, p. 3392-3401, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3392-3401.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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