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Pathogenicity and Virulence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Many bacteria and fungi produce siderophores, low molecular-weight compounds that can acquire iron from the host′s iron-binding proteins. This ability to scavenge iron has been demonstrated in many species, and has been shown to enhance the virulence of invading bacteria. Experiments have shown that virulence is greatly diminished in certain mutants that have lost the ability to obtain iron. Early work with Y. pestis showed that not even 100 million cells of a mutant that had lost the ability to acquire iron were lethal for test animals, whereas as few as 100 cells of the parent strain killed the host.
Inflammation and Infection
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Judith Hall, Christopher K. Harding
P. mirabilis urease is expressed during growth in urine:Hydrolysis of urea to carbon dioxide and ammonia.Creates alkaline urine → calcium crystal (apatite) formation and magnesium ammonium phosphate precipitates (struvite)Crystals become trapped within polysaccharides produced by attached bacterial cells → crystalline biofilms on tissues/cathetersAmmonia is toxic to urothelial cells.The urinary tract is limited in iron (an essential element for bacterial growth).Uropathogens synthesise siderophores to scavenge, chelate, and transport iron (Fe3+).Siderophores synthesised include the proteins aerobactin, yersiniabactin, and enterobactin.
Physiology of Moss-Bacterial Associations
Published in R. N. Chopra, Satish C. Bhatla, Bryophyte Development: Physiology and Biochemistry, 2019
Luretta D. Spiess, Barbara B. Lippincott, James A. Lippincott
The possibility that the growth-promoting effects of some bacteria depend on production of iron-chelating siderophores has been investigated. The Pseudomonas fluorescens-putida group is often used as an inoculant on crop plants because it increases yields by antagonizing deleterious fungi and bacteria. The production of siderophores which reduce the available iron for growth of the harmful organisms appears necessary for this response.28,29 The increase in plant growth by root-colonizing fluorescent pseudomonads in the rhizosphere is also thought to be due to siderophore production under iron-limiting conditions.30 Evidence that supports this hypothesis includes the observation that addition of iron abolishes the effect, siderophore-negative mutants do not promote growth, and addition of siderophores promotes growth. The promotion of growth and suppression of inhibition also may be due to competition for carbon compounds or the production of hormones, antibiotics, or bacteriocins.29
Drug discovery through the isolation of natural products from Burkholderia
Published in Expert Opinion on Drug Discovery, 2021
Adam Foxfire, Andrew Riley Buhrow, Ravi S. Orugunty, Leif Smith
The current understanding of natural products produced by Burkholderia supports continued efforts toward identifying potential applications for the use of these antibiotics. For instance, several siderophores have been discovered in Burkholderia and their potential use against infectious diseases is still underexplored. Siderophores have a good potential for use as a safe alternative for preservatives or therapeutics. Siderophores essentially starve the bacterium of the iron needed to carry out biological processes and thus are commonly bacteriostatic at inhibitory concentrations. Their use as an antibiotic to treat infectious diseases has not yet been fully explored and may be a useful alternative to conventual antibiotics. Interestingly, studies with Pch have changed the notion that siderophores are only bacteriostatic. Its use against E. faecalis at a four-fold higher MIC was observed to increase ROS leading to bactericidal activity. Despite studies showing a lack of in vivo activity of siderophores, in vitro studies demonstrate a broad spectrum of bacterial and fungal inhibitory properties. Thus, suggesting that additional efforts toward identifying an effective drug product in this class of compounds is needed. These compounds demonstrate good in vitro potential, and as with most natural products, they may need to be synthetically modified or formulated to afford a viable drug. Such studies are warranted, and may lead to the development of new drugs to combat resistant infections.
Potential of Application of Iron Chelating Agents in Ophthalmic Diseases
Published in Seminars in Ophthalmology, 2021
Alireza Ghaffarieh, Joseph B. Ciolino
Siderophores are essential biomolecules for the growth and proliferation of both pathogenic and non-pathogenic microbes, and their synthesis is a target for the production of new antimicrobial pharmaceuticals. The major classes of siderophores are the hydroxamate siderophores (e.g. Desferrioxamine), which are found in fungi, and the catechol siderophores (e.g. enterobactin), which are found in bacteria.30 The iron chelating proteins transferrin and lactoferrin have been involved in the uptake and transfer of iron in mammalian cells via specific pathways, preventing microbial pathogens from accessing iron. As a result, they prevent or inhibit the growth and proliferation of pathogenic organisms in mammals.31 Many chelators, especially chelating drugs, were designed based on siderophore prototypes. All the iron chelating drugs, dietary molecules and other drugs with chelating properties, such as the tetracyclines, anthracyclines, salicylates, hydroxyurea, etc., can affect iron uptake by microbial pathogens and can accordingly inhibit or promote microbial growth and proliferation.32,33 This interaction is particularly important for iron-loaded patients who are using chelating medicines and other similar drugs almost daily for their entire lives.22
Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
Published in Gut Microbes, 2021
Jasmohan S Bajaj, Amirhossein Shamsaddini, Chathur Acharya, Andrew Fagan, Masoumeh Sikaroodi, Edith Gavis, Sara McGeorge, Alexander Khoruts, Michael Fuchs, Richard K Sterling, Hannah Lee, Patrick M Gillevet
An interesting finding was the relatively higher abundance of siderophores that were present in decompensated cirrhosis even after FDR correction. Siderophores are secondary metabolites that are typically involved in iron metabolism and transport, but of late their communication and virulence potential has been described.53 Our findings of pyoverdine, enterobactin, aerobactin, and salmochelin that were higher in more advanced disease likely means that the taxa associated with their production, which are predominantly gram-negative organisms, could potentially worsen with disease.54–60 It is interesting though that although higher as disease progressed, siderophores did not significantly contribute toward death and hospitalizations when clinical biomarkers were taken into consideration. This indicates that siderophore abundance could be a co-variate of cirrhosis severity rather than independently contributory.