Metal Acquisition- Lecture 18 Flashcards
Heme
Binds fe2+
Hemoglobin
Binds heme
Hemopexin and haptoglobin
binds heme when erythrocytes have been lysed
Ferritin
Binds Fe3+ intracellularly
Transferrin
Fe3+ binding protein in serum
NRAMP 1
localizes the phagosomal membranes, pumps Mn and Fe2+ out of the phagosome, sequesters nutrients away from pathogens
Lactoferrin
Binds Fe3+ in breast milk, tears and Saliva
Hemophores
Binds heme or heme-binding proteins, found in gram-negative and gram-positive bacteria
HmuR
an example of a Ton-B dependent transporter for heme or heme-binding proteins , found in gram-negative bacteria
Which bacteria can sequester transferrin?
Corynebacteria diphtheria, has lipoprotein transporters for heme, HtaA and HtaB
Which bacteria has transferrin-binding proteins
Neisseria, Haemophilus influenza, moraxella catarrhalid
Transferrin-binding proteins
TbpA/TbpB, Ton-B dependent receptors that bind iron 3+
Lactoferrin receptors
Found in Neisseria, Treponema palladium, H. pylori and Streptococcus pneumonia
Red Queen Hypothesis
Transferrin variant Ser589, confers immunity to transferrin-binding protein A of H. influenza
Genetic heterogeneity of transferrin among hominids displays natural selection
Siderophores
Fe3+ binding proteins, high-affinity outcompetes transferrin, ex: Enterobactin produced by Enterobacteriaeae
Transport of siderophores in bacteria
Gram negative: use Ton-B dependent OM transporters, and ABC transporters at IM
Gram- positive: use diffusion across PG, then ABC transporters
Lipocalin/Siderocalin
Part of the innate immune system, binds and sequesters siderophores
Chelating subunit of siderophores
1,2-dihydroxybenzoyl subunits
Strategies to evade Lipocalin siderophore sequestering
Glycosylation or use of 3,4-dihydroxy benzoyl subunits, prevents lactoferrin from binding
Nissle 1917
Salmochelin-producing bacteria, E. coli, probiotic found solider immune to diarhea causing bacterial pathogen
Reduces Salmonella colonization in mouse models of acute colitis
Siderophore vaccination
Reduces salmonella colonization and leads to expansion of gut commensals
Add chemical conjugates to siderophores
Psoriasin
Secreted by keratinocytes, inhibits microbial growth through chelation of Zn2+
Calprotectin
Dual-binding properties for Mn2+ and Zn2+, contain Calgranulin A and B subunits which form S1 and S2 binding sites. S1 can bind both Mn and Zn, through six histidine residues, and S2 binds only Zn through 3 histidine residues and 1 aspartate residue.
Results from liver abscesses of mice infected with S. Aureus
Calprotectin sequesters zinc and manganese in abscesses
What effect does Calprotectin have on biofilm formation
Promotes biofilm formation since is disrupts the LPS synthesis pathway in H. pylori
Znu
Ton-B dependent zinc uptake system, uses ABC transporters at IM
Zinc Acquisition in yersina pseudotuberculosis
Uses both T6SS and Znu, secretes, T6SS secretes zinc binding proteins
Yersiniabactin
Zinc-siderophore found in yersinia pests, binds zinc and transports using YbtX IM transporter
Calprotectin-binding protein A
CpbA extracts Zn from calprotectin in a TonB-dependent manner, found in Neisseria meningitides
Systems for manganese acquisition
Found in all bacteria
(1): Mn2+ importers at the inner membrane, Manganese can diffuse into both positive or negative bacteria
(2): SitABC system, consists of substrate-binding sit protein, and ABC transporter, can also bind Fe3+ with low affinity
