This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kadurugamuwa, J. L. Articles by Contag, P. R. Search for Related Content PubMed PubMed Citation Articles by Kadurugamuwa, J. L. Articles by Contag, P. R.

 Previous Article  |  Next Article 

Infection and Immunity, July 2005, p. 3878-3887, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.3878-3887.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Noninvasive Biophotonic Imaging for Monitoring of Catheter-Associated Urinary Tract Infections and Therapy in Mice

Xenogen Corporation, 860 Atlantic Avenue, Alameda, California 94501

Received 12 November 2004/ Returned for modification 16 February 2005/ Accepted 9 March 2005

Urinary tract infections (UTIs) are among the most common bacterial infections acquired by humans, particularly in catheterized patients. A major problem with catheterization is the formation of bacterial biofilms on catheter material and the risk of developing persistent UTIs that are difficult to monitor and eradicate. To better understand the course of UTIs and allow more accurate studies of in vivo antibiotic efficacy, we developed a catheter-based biofilm infection model with mice, using bioluminescently engineered bacteria. Two important urinary tract pathogens, Pseudomonas aeruginosa and Proteus mirabilis, were made bioluminescent by stable insertion of a complete lux operon. Segments of catheter material (precolonized or postimplant infected) with either pathogen were placed transurethrally in the lumen of the bladder by using a metal stylet without surgical manipulation. The bioluminescent strains were sufficiently bright to be readily monitored from the outside of infected animals, using a low-light optical imaging system, including the ability to trace the ascending pattern of light-emitting bacteria through ureters to the kidneys. Placement of the catheter in the bladder not only resulted in the development of strong cystitis that persisted significantly longer than in mice challenged with bacterial suspensions alone but also required prolonged antibiotic treatment to reduce the level of infection. Treatment of infected mice for 4 days with ciprofloxacin at 30 mg/kg of body weight twice a day cured cystitis and renal infection in noncatheterized mice. Similarly, ciprofloxacin reduced the bacterial burden to undetectable levels in catheterized mice but did not inhibit rebound of the infection upon cessation of antibiotic therapy. This methodology easily allows spatial information to be monitored sequentially throughout the entire disease process, including ascending UTI, treatment efficacy, and relapse, all without exogenous sampling, which is not possible with conventional methods.

Editor: A. D. O'Brien

This article has been cited by other articles:

• Jacobsen, S. M., Stickler, D. J., Mobley, H. L. T., Shirtliff, M. E. (2008). Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis. Clin. Microbiol. Rev. 21: 26-59 [Abstract] [Full Text]  
• Lane, M. C., Alteri, C. J., Smith, S. N., Mobley, H. L. T. (2007). Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract. Proc. Natl. Acad. Sci. USA 104: 16669-16674 [Abstract] [Full Text]  
• Brady, R. A., Leid, J. G., Kofonow, J., Costerton, J. W., Shirtliff, M. E. (2007). Immunoglobulins to Surface-Associated Biofilm Immunogens Provide a Novel Means of Visualization of Methicillin-Resistant Staphylococcus aureus Biofilms. Appl. Environ. Microbiol. 73: 6612-6619 [Abstract] [Full Text]  
• Kadurugamuwa, J. L., Modi, K., Coquoz, O., Rice, B., Smith, S., Contag, P. R., Purchio, T. (2005). Reduction of Astrogliosis by Early Treatment of Pneumococcal Meningitis Measured by Simultaneous Imaging, In Vivo, of the Pathogen and Host Response. Infect. Immun. 73: 7836-7843 [Abstract] [Full Text]