Insights into Vibrio cholerae Intestinal Colonization from Monitoring Fluorescently Labeled Bacteria

PLoS Pathogens

David Alvarez¹  Simon Ringgaard¹  Brigid M. Davis¹  Matthew K. Waldor¹  Yves A. Millet²  Ulrich H. von Andrian² 

[1] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America;Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, United States of America

关键词: Vibrio cholerae;    Gastrointestinal tract;    Pathogen motility;    Mucus;    Confocal microscopy;    Small intestine;    Chemotaxis;    Gastrointestinal motility disorders;   

DOI  :  10.1371/journal.ppat.1004405

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Vibrio cholerae, the agent of cholera, is a motile non-invasive pathogen that colonizes the small intestine (SI). Most of our knowledge of the processes required for V. cholerae intestinal colonization is derived from enumeration of wt and mutant V. cholerae recovered from orogastrically infected infant mice. There is limited knowledge of the distribution of V. cholerae within the SI, particularly its localization along the villous axis, or of the bacterial and host factors that account for this distribution. Here, using confocal and intravital two-photon microscopy to monitor the localization of fluorescently tagged V. cholerae strains, we uncovered unexpected and previously unrecognized features of V. cholerae intestinal colonization. Direct visualization of the pathogen within the intestine revealed that the majority of V. cholerae microcolonies attached to the intestinal epithelium arise from single cells, and that there are notable regiospecific aspects to V. cholerae localization and factors required for colonization. In the proximal SI, V. cholerae reside exclusively within the developing intestinal crypts, but they are not restricted to the crypts in the more distal SI. Unexpectedly, V. cholerae motility proved to be a regiospecific colonization factor that is critical for colonization of the proximal, but not the distal, SI. Furthermore, neither motility nor chemotaxis were required for proper V. cholerae distribution along the villous axis or in crypts, suggesting that yet undefined processes enable the pathogen to find its niches outside the intestinal lumen. Finally, our observations suggest that host mucins are a key factor limiting V. cholerae intestinal colonization, particularly in the proximal SI where there appears to be a more abundant mucus layer. Collectively, our findings demonstrate the potent capacity of direct pathogen visualization during infection to deepen our understanding of host pathogen interactions.

【 授权许可】

CC BY