Heme Oxidase Isolated from E coli

Researchers have reported the crystal structure of ChuS, a novel heme oxygenase (HO) isolated from a highly pathogentic strain of Escherichia coli.

E coli is a normal inhabitant of the intestines of all animals, including humans. Normally E coli serves a useful function in the body by suppressing the growth of harmful bacterial species and by synthesizing appreciable amounts of vitamins. A minority of E coli strains are capable of causing human illness by several mechanisms. E coli serotype O157:H7 is a rare variety that produces large quantities of one or more related, potent toxins that cause severe damage to the lining of the intestine. These toxins (verotoxin, shiga-like toxin) are closely related or identical to the toxin produced by Shigella dysenteriae.

E coli O157:H7 was first recognized as the cause of human illness in 1982 with outbreaks in Oregon and Michigan in the United States. Following sporadic outbreaks of hemorrhagic colitis and hemolytic uremic syndrome (HUS) studies were undertaken to isolate and characterize the responsible organism. After the E coli outbreak in the northwestern U.S. in 1993 in which some small children died from eating hamburgers from a fast food restaurant, the U.S. meat industry introduced additional inspection programs to eliminate or prevent pathogenic bacteria from contaminating the meat supply.

However, while original outbreaks of E coli O157:H7 were associated with undercooked ground beef, later outbreaks were traced to apple cider, vegetables, and drinking or swimming in contaminated water. A recent massive outbreak in Japan (more than 11,000 cases) was traced to white radish seeds imported from the U.S.

Investigators at Queen's University (Kingston, ON, Canada) isolated the heme oxygenase ChuS, an enzyme that catabolizes hemoglobin and releases its iron atom for metabolic use by the bacteria. The crystal structure of the protein displayed a previously uncharacterized fold that is unique compared with other characterized HOs. ChuS was capable of using ascorbic acid or cytochrome P450 reductase-NADPH as electron sources for heme oxygenation. Based on sequence analysis, ChuS is present in many bacteria, although not in the E coli K-12 strain. The N- and C-terminal halves of ChuS are each a functional HO. These findings were published in the November 7, 2005, online edition of the Proceedings of the [U.S.] National Academy of Sciences.

"This discovery opens the door for studying the function of heme iron in this strain of E coli, and may lead to an understanding of how to therapeutically isolate the protein to keep the bacteria from thriving,” said senior author Dr. Zongchao Jia, professor of biochemistry at Queen's University.