SIDEROPHORE Tanvi Raulaji M.Sc Department of Biosciences, Bakrol
. 2 Definition A siderophore is a small, high affinity iron chelating molecule produced by microorganism such as bacteria and fungi. These organisms release siderophores to scavenge iron from their environment which is essential for their growth and metabolism Siderophores bind to iron tightly and transport it back to the microorganism, facilitating its uptake . Kloepper et al. were first to demonstrate the importance of siderophores. The siderophores producing organism are Azotobacter , pseudomonas, Bacillus , Streptomyces .
1] CATECHOLATE This is known as pyrocatechol & 1,2 dihyroxybenzene . It is ortho isomer of 3 isomeric benzendiol . This colour less compound occur in trace amount. In iron limited medium, Azotobacter vinelandii produce 3 catecholate siderophore namely Tricatecholate Protochelin Dicatecholate Azotochelin Monoactecholate Aminochelin Example ENTEROBACTIN . 5
ADD A FOOTER 6 Enterobactin It was First Tricatechol Siderophore, isolated from E.coli Aerobacter aerogenes Salmonella typhimurium Enterobactin are produced by bacteria of family Enterobacteriaceae inciudes all strain of E.coli having high affinity for iron Enterobactin is strongest siderophore having the capacity to chelate iron even from the environment where concentration of iron is low. Enterobactin are synthesized with help of active transport mechanism for transport and capturing iron.
Ferrichrome type hydroxamate siderophore are special ecological interest because of their production by many soil fungi. Hydroxamate siderophore are generally produced by fungi Zygomycotina Ascomycotina Deuteromycotina Hydroxamate siderophore formed hexadentate,Tetradentates , Bidentate ligands. Certain ferrichrome derivatives display antibiotic activity and have been designated as Ferrimycine . ADD A FOOTER 7 2] HYDROXAMATE
. 8 Aferrioxamine These are linear trihydroxamates siderophores produced by Streptomyces and nocardia. These are used therapeutically for the binding of excess blood iron in treatment of thalsaemia . Ferrichrome These are cyclic trihydroxamate siderophore. This are cyclic hexapeptide siderophore composed of 3 N acyl N hydroxyl Ornithine 2 variable amino acid Glycine linked by peptide bond. Ferrichrome produced by Fungus Ustilago sphaerogena was first siderophore to be isolated and shown to be growth Factor for other microb es.
. 9 Aerobactin Aerobactin is bacterial iron chelating agent found in E.coli This hydroxamate siderophore is an exogeneous siderophore of Pseudomonas (Marine origin) K.pneumonia A.aerogenes E.coli It is a virulence factor enabling E.coli to sequester iron in iron poor environment Under iron limiting condition the Pseudomonas spp. Produced aerobactin a dihydroxamate siderophore previously found only in family Enterobacteriaceae .
3] CARBOXYLATE This is novel class of siderophore whose membrane Rhizoferrin is composed of Di amino propane symmetrically acylated with citric acid via amine bonds. Rhizoferrin is only known Carboxylate siderophore produced by fungi (Zygomycetes) Carboxylate Sidrophore like Rhizobacteria Staphloferrin Rhizopherrin Both fungi and bacteria produce Rhizoferrin , fungi produce only R- rhizoferrin Bacteria produce enantio S- rhizoferrin . 10
4]Mixed Ligand Lysine Derivative : Myobactin Mycobactin are 2 hydroxy phenyl oxazoline contain siderophore molecule for the acquisition of iron. Two chemical structure of siderophore produce by Mycobacterium tuberculosis are more lipophilic & More hydrophilic in nature. M. tuberculosis produce only mycobactin class of siderophore molecule, which contain this Sali cyclic acid derived moiety. Ornithine Derivative : pyoverdine Pyoverdine contain a dihydroxy quinoline derivative. A variety of Fluorescent chromopeptide siderophore termed Pseudobactin & Pyoverdines are synthesized by pseudomonas. . 11
Histamine Derivative : Anguibactin Two important siderophore mediated iron uptake system have been foundn in these bacteria Fluroesent Pyochelin . 12 It’s isolated from marine pathogen Vibrio anguillarum Anguibactin act as inhibitor for uptake of iron by living cell.
Significance of Siderophores Nutrient Acquisition: Siderophores play a crucial role in helping microorganisms acquire iron, a key nutrient that supports essential cellular processes like DNA synthesis, respiration, and metabolism. 2. Competition and Survival: In iron-limited environments, microorganisms that produce siderophores have a competitive advantage over those that don't, as they are better able to secure this vital resource. This is especially important in microbial communities where multiple species compete for limited resources. 3. Pathogenesis: Some pathogenic bacteria rely on siderophores to obtain iron from their host during infection. Since the host actively limits the availability of free iron as a defense mechanism (a process called "nutritional immunity"), siderophores help pathogens overcome this barrier and establish infections. For example, pathogens like Pseudomonas aeruginosa and Escherichia coli produce siderophores to thrive in iron-limited environments within the host. ADD A FOOTER 13
. 4. Agricultural Use: Siderophores are also being studied for their potential use in agriculture. Some beneficial soil microbes produce siderophores that can enhance plant growth by increasing the availability of iron in the soil, aiding in nutrient uptake, and inhibiting the growth of plant pathogens. 5. Medical and Therapeutic Applications: Siderophore-based systems are being explored for therapeutic purposes, such as in antibiotic development. By targeting iron acquisition mechanisms in pathogens, new treatments could be developed that disrupt the ability of harmful microbes to thrive in the human body. In summary, siderophores are significant for their role in microbial survival, competition, and pathogenesis, with broader implications forhuman health, agriculture and biotechnology. ADD A FOOTER 14
Advantages 1.Efficient Iron Acquisition: Siderophores allow microorganisms to acquire iron from extremely low-iron environments by binding iron with high affinity. This is crucial for microbial growth and survival, especially in competitive environments. 2. Ecological Fitness: Siderophore-producing organisms have a competitive edge in environments where iron is scarce, as they can efficiently scavenge this essential nutrient, promoting their survival and proliferation over non-siderophore producers. 3. Host-Microbe Interactions: In the context of pathogenic bacteria, siderophores enhance the ability of microbes to infect and grow within a host by outcompeting the host's iron-sequestering defenses. This can make siderophore-producing pathogens particularly virulent. 4. Agricultural Benefits: Siderophores can enhance plant growth by increasing iron availability in the soil, which helps plants absorb more nutrients. Some beneficial microbes use siderophores to suppress plant pathogens, acting as natural biocontrol agents. 5. Medical Applications: Siderophores are being explored for medical use, such as drug delivery and iron chelation therapies. They can potentially be used to deliver antibiotics directly to bacterial cells by exploiting their iron-uptake pathways, increasing drug efficacy.--- ADD A FOOTER 15
Disadvantages 1.Host Defense Evasion: In the context of human health, siderophores are a disadvantage because they help pathogens evade host immune defenses. Many pathogenic bacteria use siderophores to steal iron from host tissues, contributing to the severity of infections. This makes it harder for the host to limit bacterial growth. 2. Energetic Cost: Producing siderophores can be energetically expensive for microorganisms. The synthesis, secretion, and reuptake of siderophores require significant resources, which could be a disadvantage in environments where energy and nutrients are limited. 3. Exploitation by Other Organisms: Some microorganisms, known as "cheaters," do not produce siderophores themselves but can exploit the siderophores produced by others. This can be a disadvantage for siderophore-producing organisms that end up supplying iron to their competitors without benefiting directly. 4. Limited Effectiveness in Certain Environments: In environments where iron is already abundant, siderophore production may not confer a significant advantage. Moreover, some microorganisms or host systems have mechanisms that directly degrade siderophores, neutralizing their effectiveness. 5. Potential Environmental Harm: In agricultural use, there are concerns that introducing or overusing siderophore-producing microbes could disrupt natural microbial communities, leading to unforeseen ecological consequences. Additionally, overuse could result in resistance mechanisms evolving in plant pathogens. ADD A FOOTER 16