New compound to control many virulence genes in Listeria monocytogenes

Fluoro-phenyl-styrene-sulfonamide inhibits key bacterial virulence component.

Cantaloupe contaminated with the bacterium Listeria monocytogenes killed 29 people in the U.S. this year in the deadliest foodborne outbreak since 1924, but the pathogen usually strikes in less public ways, quietly sickening an average of 1,600 people per year, according to the CDC. The authors of a study in mBio this week screened 57,000 small molecules to find one compound that can stop Listeria monocytogenes in its tracks. This needle-in-the-haystack approach has turned up a compound that could lead to novel therapeutics for listeriosis and other infections.

Palmer et al. targeted an Achilles tendon for many Gram positive bacteria, the stress responsive alternative sigma factor “σB”, since it poses a small target that, when struck, could bring down the entire pathogen. In Listeria, the σB gene controls the transcription of more than 150 other genes, many of which contribute to virulence and survival inside the human host. After screening tens of thousands of different small molecules, both synthetic and natural, for their activity against σB, the authors settled on fluoro-phenyl-styrene-sulfonamide (FPSS), a compound that specifically inhibits activity of σB and doesn’t pack any nasty side effects for mammalian cells. This shuts down many of Listeria’s virulence factors and inhibits invasion of the intestinal lining. As a bonus, FPSS could well prove effective against other pathogens that rely on σB, including Staphylococcus aureus (the cause of a wide range of maladies, from pimples to pneumonia) and Bacillus anthracis (the delightful bacterium that brought you Anthrax).
The authors point out that FPSS could serve not only as a therapeutic, but also as a tool for studying the regulatory networks that enable Listeria monocytogenes and other Gram-positive pathogens to invade and take advantage of the human host. An ongoing problem that has come to the public’s attention only when hundreds were sickened in the outbreak earlier this year, perhaps listeriosis is overdue for this exploration and for some new antibiotic therapy options.
Source: mBio ASM, 2012, http://mbio.asm.org/content/2/6/e00241-11.executive-summary