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Clostridium difficile is a spore-forming, anaerobic, toxin-producing bacterium that is a "common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis in patients receiving antibiotic therapy." C. difficile superinfection after oral antibiotic therapy, leading to potentially fatal pseudomembranous enterocolitis, has been an increasingly severe public health problem. Indeed, many primary physicians now consider it wise to warn outpatients on antibiotics to seek immediate consultation if they develop severe diarrhea.

C. difficile is present at low levels in the gut flora of about 3% of adults. These people however show no symptoms and do not need to be treated. The infection occurs when a person is treated with antibiotics targeted against other bacteria. The disease is for the most part nosocomial. Patients who are hospitalized come in contact and are often inoculated with the bacteria. When the patient is treated with antibiotics, especially those with a broad range of activity, the normal gut flora is disrupted, and C. difficile, with its multi-drug resistance, experiences overgrowth. The bacteria releases large quantities of enterotoxins (toxin A) and cytotoxins (toxin B), causing pseudomembranous enterocolitis.

scanning electron micrograph of C. difficile

History

In 1935, Hall and O’Toole first isolated the bacteria from the stools of newborns and described it. They named it Bacillus difficilis because it was hard to isolate and grew very slowly in culture.

C. difficile is an important pathogen that is currently increasing in its prevalence world-wide. A complete genome sequence would enable geneticists to come up with a more direct and efficient treatment against the pathogen. The genetic material encodes for antimicrobial resistance, production of toxins (virulence), host interaction (adaptations for survival and growth within the gut environment), and the production of surface structures. The understanding of how these genes interact with their environment will be useful in developing therapies against C. difficile associated diseases.

Genome Structure

Sebaihia et al (2006) determined the complete genomic sequence of C. difficile strain 630, a highly virulent and multidrug-resistant strain. It was found that the genome consists of a circular chromosome of 4,290,252 bp and a plasmid, pCD630, of 7,881 bp. The chromosome encodes 3,776 predicted coding sequences (CDSs), with resistance, virulence, and host interaction genes, while the plasmid carries only 11 CDSs, none of which has any obvious function. C. difficile has a highly mobile genome, with 11% of the genome consisting of mobile genetic elements, mostly in the form of conjugative transposons. Conjugative transposons are mobile genetic elements that are capable of integrating into and excising from the host genome and transferring themselves, and are responsible for the evolutionary acquisition by C. difficile of genes involved in resistance, virulence, and host interactions. Some of the mobile elements are prophage sequences. Host interaction genes involve genes that code for metabolic capability adaptations for survival and growth within the gut environment.

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