Discovery and characterization of a novel heme-iron acquisition pathway from enterohemorrhagic e. coli

Iron is an essential nutrient bacteria must acquire to survive within their niche, which can be a major barrier during colonization and pathogenesis. Therefore, pathogenic microorganisms have developed pathways to utilize heme as an iron source. Heme oxygenases are the canonical enzymes that degrade heme and require diatomic oxygen in the enzymatic mechanism. However, the hemolytic enteric bacteria Escherichia coli O157:H7 and Vibrio cholerae do not contain an equivalent enzyme and are subjected to low oxygen tensions during pathogenesis. In this work, we establish the function of ChuW and ChuY from E. coli O157:H7. Our data indicate ChuW is a radical S-adenosylmethionine methyltransferase that degrades heme to release the heme-iron and produce the novel tetrapyrrole anaerobilin. ChuY is the downstream enzyme to ChuW that can reduce anaerobilin using NADPH as a cosubstrate. Thus, ChuW and ChuY represent a novel oxygen-independent heme degradation pathway.