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Infection and Immunity, May 2001, p. 3350-3358, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3350-3358.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Visualizing Pneumococcal Infections in the Lungs of Live Mice Using Bioluminescent Streptococcus pneumoniae Transformed with a Novel Gram-Positive lux Transposon

Kevin P. Francis,1,* Jun Yu,1 Carolyn Bellinger-Kawahara,1 Danny Joh,1 Matthew J. Hawkinson,1 Grace Xiao,1 Tony F. Purchio,1 Michael G. Caparon,2 Marc Lipsitch,3 and Pamela R. Contag1

Xenogen Corporation, Alameda, California 945011; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 631302; and Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 021153

Received 4 December 2000/Returned for modification 18 January 2001/Accepted 24 January 2001

Animal studies with Streptococcus pneumoniae have provided valuable models for drug development. In order to monitor long-term pneumococcal infections noninvasively in living mice, a novel gram-positive lux transposon cassette, Tn4001 luxABCDE Kmr, that allows random integration of lux genes onto the bacterial chromosome was constructed. The cassette was designed so that the luxABCDE and kanamycin resistance genes were linked to form a single promoterless operon. Bioluminescence and kanamycin resistance only occur in a bacterial cell if this operon has transposed downstream of a promoter on the bacterium's chromosome. S. pneumoniae D39 was transformed with plasmid pAUL-A Tn4001 luxABCDE Kmr, and a number of highly bioluminescent colonies were recovered. Genomic DNA from the brightest D39 strain was used to transform a number of clinical S. pneumoniae isolates, and several of these strains were tested in animal models, including a pneumococcal lung infection model. Strong bioluminescent signals were seen in the lungs of the animals containing these pneumococci, allowing the course and antibiotic treatment of the infections to be readily monitored in real time in the living animals. Recovery of the bacteria from the animals showed that the bioluminescent signal corresponded to the number of CFU and that the lux construct was highly stable even after several days in vivo. We believe that this lux transposon will greatly expand the ability to evaluate drug efficacy against gram-positive bacteria in living animals using bioluminescence.

* Corresponding author. Mailing address: Xenogen Corporation, 860 Atlantic Ave., Alameda, CA 94501. Phone: (510) 291-6100. Fax: (510) 291-6196. E-mail: kfrancis{at}xenogen.com.

Infection and Immunity, May 2001, p. 3350-3358, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3350-3358.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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