Host-induced epidemic spread of the cholera bacterium - PubMed (original) (raw)

Host-induced epidemic spread of the cholera bacterium

D Scott Merrell et al. Nature. 2002.

Abstract

The factors that enhance the transmission of pathogens during epidemic spread are ill defined. Water-borne spread of the diarrhoeal disease cholera occurs rapidly in nature, whereas infection of human volunteers with bacteria grown in vitro is difficult in the absence of stomach acid buffering. It is unclear, however, whether stomach acidity is a principal factor contributing to epidemic spread. Here we report that characterization of Vibrio cholerae from human stools supports a model whereby human colonization creates a hyperinfectious bacterial state that is maintained after dissemination and that may contribute to epidemic spread of cholera. Transcriptional profiling of V. cholerae from stool samples revealed a unique physiological and behavioural state characterized by high expression levels of genes required for nutrient acquisition and motility, and low expression levels of genes required for bacterial chemotaxis.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Human-shed V. cholerae are hyperinfectious in competition assays in infant mice. a, b, Freshly isolated stool samples from six patients (representing experiments 1, 2 and 3 on the x axes in a and b) were either mixed directly with _in vitro_-grown DSM-V984 (a), or incubated in local pond water for 5 h before mixing (b), and then used for intragastric infection of animals. Data points represent the output ratio of stool-derived V. cholerae to _in vitro_-grown competitor strain after correction for deviations in input ratios. Each data point represents the output from a single animal and symbols and colours are used to facilitate visual discrimination of data values. The geometric mean is indicated by a horizontal bar. n, total number of animals per experiment.

Figure 2

Figure 2

Transcription profile of human-shed V. cholerae. Cluster diagram showing the whole-genome expression profile of V. cholerae recovered from the stools of three ICDDR patients (left panel). Patient samples are labelled A–C and replicate arrays are indicated by the numbers 1–4. The dendrogram shows tight clustering of technical replicates. The right panel is a cluster diagram of genes showing consistent differential regulation from patients A, B and C. Fold changes relative to V. cholerae grown in vitro were calculated using the average values from the quadruplicate arrays shown on the left, and are schematically represented here. Red indicates a minimum twofold increase in expression; green represents a minimum twofold reduction in expression. Representative genes are listed and their relative location indicated by an arrow. See Supplementary Information for a complete list with relative fold changes.

Similar articles

Cited by

References

    1. Cash RA, et al. Response of man to infection with Vibrio cholerae. I. Clinical, serologic, and bacteriologic responses to a known inoculum. J. Infect. Dis. 1974;129:45–52. - PubMed
    1. Gitelson S. Gastrectomy, achlorhydria and cholera. Israel J. Med. Sci. 1971;7:663–667. - PubMed
    1. Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270:467–470. - PubMed
    1. Heidelberg JF, et al. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature. 2000;406:477–483. - PMC - PubMed
    1. Freter R, Smith HL, Sweeney FJ. Enumeration of cholera vibrios in faecal samples. J. Infect. Dis. 1961;109:31–34. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources