This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zahid, M. S. H.
Right arrow Articles by Faruque, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zahid, M. S. H.
Right arrow Articles by Faruque, S. M.

 Previous Article  |  Next Article 

Infection and Immunity, November 2008, p. 5266-5273, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00578-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Effect of Phage on the Infectivity of Vibrio cholerae and Emergence of Genetic Variants{triangledown}

M. Shamim Hasan Zahid,1 S. M. Nashir Udden,1 A. S. G. Faruque,1 Stephen B. Calderwood,2 John J. Mekalanos,3 and Shah M. Faruque1*

Molecular Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka-1212, Bangladesh,1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115,2 Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 021153

Received 12 May 2008/ Returned for modification 24 June 2008/ Accepted 3 September 2008

Seasonal epidemics of cholera in Bangladesh are self-limited in nature, presumably due to phage predation of the causative Vibrio cholerae during the late stage of an epidemic, when cholera patients excrete large quantities of phage in their stools. To further understand the mechanisms involved, we studied the effect of phage on the infectivity and survival of V. cholerae shed in stools. The 50% infectious dose of stool vibrios in infant mice was ~10-fold higher when the stools contained a phage (1.8 x 103 to 5.7 x 106 PFU/ml) than when stools did not contain a detectable phage. In competition assays in mice using a reference strain and phage-negative cholera stools, the infectivity of biofilm-like clumped cells was 3.9- to 115.9-fold higher than that of the corresponding planktonic cells. However, the difference in infectivity of these two cell populations in phage-positive stools was significantly less than that in phage-negative stools (P = 0.0006). Coculture of a phage and V. cholerae or dilutions of phage-positive cholera stools in nutrient medium, but not in environmental water, caused rapid emergence of phage-resistant derivatives of the bacteria, and these derivatives lost their O1 antigen. In cholera stools and in intestinal contents of mice prechallenged with a mixture of V. cholerae and phage, the bacteria remained completely phage susceptible, suggesting that the intestinal environment did not favor the emergence of phage-resistant derivatives that lost the O1 antigen. Our results indicate that phages lead to the collapse of epidemics by modulating the required infectious dose of the bacteria. Furthermore, the dominance of phage-resistant variants due to the bactericidal selective mechanism occurs rarely in natural settings, and the emerging variants are thus unable to sustain the ongoing epidemic.

* Corresponding author. Mailing address: Molecular Genetics Laboratory, ICDDR,B, Mohakhali, Dhaka-1212, Bangladesh. Phone: 880 2 9886464. Fax: 880 2 8812529. E-mail: faruque{at}icddrb.org

{triangledown} Published ahead of print on 15 September 2008.

Editor: V. J. DiRita

Infection and Immunity, November 2008, p. 5266-5273, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00578-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»