Mechanisms Of Functioning And Control Of Heme Uptake In Gram-Negative Pathogenic Bacteria

Iron is one of the most important micronutrients used by bacteria, essential for their basic metabolism. Over 70% of bioavailable iron in mammals is in the heme molecule. Gram-negative pathogenic bacteria during colonization and infection of the host organism use heme as the main source of iron. Bacteria have developed two types of outer membrane receptors/transporters involved in the heme uptake. The first one focuses on the receptors recognizing heme or hemoproteins and transporting the ligand through the outer membrane. The second type of receptor recognizes and takes up heme in a complex with a hemophore, a small protein released from a bacterial cell. Microorganisms have developed appropriate transcriptional and post-transcriptional mechanisms that control the iron/ heme uptake, protecting against their toxic excess. One of the most important regulatory systems is based on the functioning of the Fur protein, a repressor of gene transcription. More and more is known about the role of non-coding RNAs in post-transcriptional regulation of Fur regulon gene expression.

1. Introduction. 2. Hem and heme compounds in the host organism. 3. Binding and transport of heme through bacterial wall and membranes. 3.1. Active transport of heme through the outer membrane of Gram-negative bacteria. 3.2. ATP-dependent transport across the cytoplasmic membrane. 4. Regulation of gene expression of heme uptake. 4.1. Characteristics of Fur protein. 4.2. Fur-DNA interaction. 4.3. Regulation of fur gene expression in E. coli. 4.4. Fur as a global regulator of gene expression in E. coli. 4.5. Other mechanisms for controlling the expression of heme uptake genes. 5. Summary