The anaerobe, Fusobacterium nucleatum, is an opportunistic oral pathogen that is associated with colorectal cancer. Escherichia coli O157:H7 and Vibrio cholera, two facultative anaerobes, cause severe gastrointestinal illness. The ability of these organisms to establish infection in the anoxic colon depends on the acquisition of iron, an essential nutrient. To meet this nutritional requirement, all three of these organisms possess heme uptake/utilization operons, designated chu (E. coli O157:H7), hmu (F. nucleatum), and hut (V. cholera), that enable the organisms to acquire heme, the most abundant source of iron in the human host. Once heme enters the cell, the porphyrin ring is broken open in an O2-independent reaction that is catalyzed by anaerobilin synthase, a radical S-adenosylmethionine-dependent enzyme. The reaction generates a linear tetrapyrrole, termed anaerobilin and releases iron that can be used for other cellular processes. Anaerobilin is cytotoxic due to its high level of conjugation and a reactive methylene group. To protect itself from the cytotoxicity of labile heme and anaerobilin, F. nucleatum encodes HmuF, which binds tightly to heme and traffics it to anaerobilin synthase for degradation. HmuF then catalyzes a four-electron reduction of anaerobilin, removing conjugation and the reactive methylene group. In E. coli O157:H7, two structurally distinct proteins, ChuS and ChuY, fulfill the function of HmuF in that ChuS traffics heme to anaerobilin synthase and ChuY catalyzes a four-electron reduction of anaerobilin. Strikingly, V. cholera does not contain a homolog for ChuS, ChuY or HmuF, raising questions about how the organism protects itself during heme degradation. We showed that HutZ of V. cholera binds tightly to heme (thereby preventing labile heme toxicity) and sequesters it from HutW, preventing heme degradation. Counterintuitively, V. cholera seemingly avoids anaerobilin toxicity by simply preventing its formation. In sum, structurally distinct chu, hmu, and hut operons have functionally converged to protect the cell from anaerobilin accumulation and heme cytotoxicity.