Biochemical Signals Guide Intestinal Pathogens

Researchers have found that Escherichia coli O157:H7, an intestinal pathogen that produces large quantities of one or more potent toxins that cause severe damage to the lining of the intestine, responds to biochemical signals transmitted by bacteria of the intestinal flora as well as hormones from intestinal cells in order to locate sites of attachment--a prelude to activation of toxin-producing genes.


The inter-bacterial communication system known as quorum sensing (QS) utilizes hormone-like compounds referred to as autoinducers to regulate bacterial gene expression. The QS system used by O157:H7 is the LuxS/autoinducer 2 (AI-2) system extensively involved in interspecies communication. The autoinducer AI-2 is a furanosyl borate diester whose synthesis depends on the enzyme LuxS.


In the current study, published July 7, 2003, in the online edition of the Proceedings of the National Academy of Sciences, investigators at the University of Texas Southwestern Medical Center (Dallas) showed that an O157:H7 luxS mutant, unable to produce the bacterial autoinducer, still responded to a eukaryotic cell signal to activate expression of its virulence genes. They identified this signal as the hormone epinephrine and showed that beta- and alpha-adrenergic antagonists blocked the bacterial response to this hormone.

The authors speculated that their study could lead to the development of beta blockers as a therapy to impede this cellular signaling system, causing the harmful bacteria to pass blindly through the digestive tract. "You are not really attacking the bacteria per se,” explained first author Dr. Vanessa Sperandio, assistant professor of microbiology at the University of Texas Southwestern Medical Center. "You are just rendering it blind. The bacteria will not activate the virulent genes unless it knows where it is. If it cannot activate the things it needs to bind to the intestine, it will be washed away.”




Related Links:
University of Texas Southwestern Medical Center