User:Caleb Holaway/Sandbox 1: Difference between revisions

Pathogenic bacteria require several metal cofactors for enzymatic activity and, therein, performance of biochemical processes. As a result, these parasites have evolved mechanisms by which they can uptake essential nutrients from their host.  Though many of these ions are present in the cytosol of host cells or in the extracellular matrix of host tissue at various concentrations, thereby making sequestering these materials relatively simple, iron presents an interesting obstacle in terms of accessibility for bacteria in that it exists mainly in erythrocytes in the heme compound hemoglobin, though it also exists in storage compounds such as ferritin, lactoferrin, transferrin, and hemosiderin. As a result, pathogens have evolved several means by which heme and hemoglobin can be uptaken by cells and degraded for abstraction of iron <ref>DOI: 10.1086/518040</ref>

M. Tuberculosis (Mtb) is a droplet-spread bacteria which causes tuberculosis. The bacterium lives and reproduces within the phagosomes of alveolar macrophages.  In 2018 alone, nearly 1.5 million people died from tuberculosis, making it among the top 10 diseases in terms of mortality.  Being that iron is relatively scarce within alveolar macrophage phagosomes, Mtb has evolved intricate means by which iron is uptaken.  The sheer number of genes dedicated to these processes is an indication of the complex evolution of this uptake.  For instance, M. tuberculosis have approximately 35 known genes alone associated only with the production of salicylate-derivative iron siderophores termed mycobactins.

Periplasmic binding proteins (PBPs) are non-enzymatic receptors that bacteria use to sense small molecules such as carbohydrates, amino acids, and ions, and transport them into the cytoplasm.  These sorts of proteins are ubiquitous in both gram-negative and gram-positive bacteria, appearing in gram-positive bacteria as membrane-anchored lipoproteins.  The glucose/galactose binding protein (<scene name='84/842887/Gbbp/4'>GBBP</scene>) of E. Coli is amongst the best studied of these proteins.    These proteins typically exhibit a “Venus fly-trap” appearance, consisting of two globular domains connected by a small hinge region.  The hinge-like appearance is evident in GBBP.  These proteins often also work in conjunction with an ABC-binding cassette transporter which catalyzes the movement of the substance at hand across the cytoplasmic membrane.