Mechanisms of bacterial heme uptake and degradation: Diverse strategies for ring opening
Year: 2025
Type: article
Abstract: Iron acquisition by bacterial pathogens is critical for their survival and virulence within the host. Heme represents a viable source of iron by which pathogens overcome the limited iron availability and establish infection. Over the past decade several new paradigms in bacterial heme degradation have been identified. Herein, we will briefly discuss the mechanisms by which bacterial pathogens acquire and utilize heme with a particular focus on the three major classes of heme-degrading enzymes: the canonical heme oxygenases (HO), the non-canonical HOs, and the class C radical SAM methyl transferases. The canonical HO enzymes typified by the gram-negative pathogens Pseudomonas aeruginosa and Neisseriae meningitidis were shown to be structurally and mechanistically similar to the eukaryotic HO enzymes. In contrast, the non-canonical HOs of the gram-positive pathogen Staphylococcus aureus and Mycobacterium tuberculosis have a distinct ferredoxin-like structural fold and extreme heme ruffling that gives rise to alternate heme metabolites. Enteric pathogens such as E. coli O157:H7 and Vibrio cholera encode a heme-dependent radical SAM methyl transferase that opens the porphyrin ring in an oxygen-independent manner essential in the anoxic environment of the gut. All three classes of heme-degrading enzymes provide an advantage for survival within the host, while also yielding metabolites that play a role in bacterial adaptation and virulence. Therefore, a complete understanding of the distinct mechanisms of heme degradation and the role of the unique heme metabolites will provide a platform for the development of antibacterial strategies targeting heme catabolism. Heme degrading enzymes of bacterial pathogens vary based on their physiological niche and oxygen availability. The canonical-HO enzymes release iron yielding biliverdin IX and CO. The non-canonical HO enzymes on ring opening release either CH 2 O and staphylobilin or retain the meso ‑carbon as the formyl-bilin as in the case of mycobilin. Anaerobic heme degradation by the class C radical SAM methyl transferases opens the porphyrin ring through addition of a methylene radical. • Iron is essential for survival and virulence of bacterial pathogens. • Heme is a viable source of iron within the host. • Heme degrading enzymes vary depending on the host's physiological niche. • Heme metabolites function as signaling molecules in adaptation and virulence.
Authors: Kieran Johnson, Fengtian Xue, Angela Wilks
Institution: University of Maryland, Baltimore
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,220
OpenAlex ID: W4413118457