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Cholera is a disease arising from contaminated water supplies; in the United States, contaminated shellfish, eaten raw, are the major source of infection. The causative agent, Vibrio cholerae, attaches itself to the brush border of the villous absorptive cells of the small intestine of its victim. There it produces the cholera toxin, a multimeric protein including 5 subunits arranged as a doughnut, shown in Figure 1. The toxin is internalized by the intestinal cells where it activates G-proteins leading to massive fluid and electrolyte loss. Control of the production of the cholera toxin is via the ToxR transcription factor, which activates the operon encoding the cholera protein. This operon also contains the ToxT gene, whose product activates several other virulence factors. The complete genome of V. cholerae, encoding its toxin toolkit, can be examined now in Entrez Genomes. From www.ncbi.nlm.nih.gov/Entrez, select the Genomes database. —DW

Figure 1

Cn3D view of cholera toxin B-Pentamer complexed with
Metanitrophenyl-Alpha-D-Galactose (MMDB entry 12741,
PDB code 1EE1).

View the Blueprint for a Motile, Hardy Bug

Pseudomonas aeruginosa is an opportunistic pathogen that is extremely resistant to disinfectants and antibiotics used to control it—the bug can live quite happily on a bar of soap. At 6.26 megabases, it is the largest bacterial genome sequenced to date.

P. aeruginosa is also highly motile due to a flagellum that it builds with the help of a couple dozen genes. Using this flagellum, P. aeruginosa can travel to places in the body that other microbes do not normally reach, such as the respiratory sinuses, where it can inflict lethal damage. In fact, P. aeruginosa causes a wide range of infections in people who are ill or have damaged immune systems, and is particularly dangerous to people with cystic fibrosis or on respirators. About 80% of treated infections are still fatal.

The microbe has 5,565 protein-coding genes, including the blueprint for its flagella, within a six-million-base genome that can now be explored via Entrez Genomes. From www.ncbi.nlm.nih.gov/Entrez, select the Genomes database.

The complete sequence can be found at ftp://ncbi.nlm.nih.gov/genbank/genomes/bacteria/Paer/. —DW

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