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Metal Ion Dependent Antibiotics in Chemotherapy
Published in Astrid Sigel, Helmut Sigel, Metal Ions in Biological Systems, 2004
David H. Petering, Chuanwu Xia, William E. Antholine
The structures of albomycin bound to either fluA or fluD show that the primary binding interaction between the drug and each protein involves the siderophore mimic [137,139]. It appears that either protein can accommodate a wide variety of other structures coupled to the Fe(III)-hydroxamate. Supporting this conclusion are dissociation constants for the complexes of ferrichrome and albomycin with fluD of 1 × 10−6 and 5 × 10−6, respectively [140]. On this basis, albomycin would compete effectively with ferrichrome for uptake into E. coli. These findings encourage the idea that highly effective antibiotics may be synthesized by linking bacterial cytotoxic molecules to siderophores [136].
Iron metabolism in Pseudomonas aeruginosa biofilm and the involved iron-targeted anti-biofilm strategies
Published in Journal of Drug Targeting, 2021
Yapeng Zhang, Xuanhe Pan, Linqian Wang, Liyu Chen
Pseudomonas aeruginosa produces two endogenous siderophores (pyoverdine and pyochelin) capable of chelating Fe3+. Compared to pyochelin, pyoverdine has higher iron affinity [11]. In a medium containing sufficient iron, the pyoverdine mutant (PvdA–) strain only formed a flat and uniform bacteria layer on the glass surface, while the pyochelin mutant (PchA–) produced a complex biofilm similar to the wild type [12], indicating that pyoverdine has a greater impact on the development of biofilm. Pyoverdine has dual action of providing essential nutrient for biofilm development as well as being a signal molecule for the expression of major virulent factors including extracellular protease and exotoxin A [13,14]. P. aeruginosa can also exploit xenosiderophores, such as enterobactin (a catechol siderophore produced by Escherichia coli), vibriobactin (a catechol siderophore produced by Vibrio cholera), ferrichrome (a hydroxamate siderophore produced by Aspergillus nidulans and Penicillium chrysogenum), yersiniabactin (produced by Yersinia pestis) and exochelin (produced by Mycobacterium neoaurum) to obtain iron [15–19]. Other researches have shown that ferrichrome uptake-system could affect the bacteria’s biofilm development and elastase activity [20]. Under restricted iron conditions, the iron-uptake system mediated by exochelin in P. aeruginosa is critical for biofilm formation [12].
Subtle relationships between Pseudomonas aeruginosa and fungi in patients with cystic fibrosis
Published in Acta Clinica Belgica, 2022
Kaicheng Yan, Hong Yin, Jin Wang, Yun Cai
Iron is essential to all forms of life. In bacteria, iron is involved in a variety of metabolic processes, including respiration and key enzymatic reactions [9]. PA relies on a complex iron homeostasis mechanism to ensure that iron is adequate for metabolism and to prevent iron-induced toxicity. Iron is also an essential nutrient and fulcrum of the pathogenesis of AF [10]. In the early stages of pulmonary infection in CF, the availability of iron for living microflora is strictly limited. Because the concentration of free iron in mammals is very low, it will be further reduced in the process of infection [11]. Aims of the struggle between PA and fungi are to make sufficient amounts of soluble iron for itself and protect its habitat from microbial competitors. Therefore, they can produce a variety of antibiotic active compounds and Fe3+-complexing agents [12]. PA can produce inorganic Fe3+-complexing agents or fix it by complexation. The intracellular iron carrier ferritin plays an important role in iron homeostasis of filamentous fungi, and it is known to be involved in various iron-related metabolic processes. In CF, the ferrichrome produced by AF is involved in storage, intracellular and intracellular iron distribution, oxidative stress tolerance, germination, and sexual development [13]. PA can use heterologous iron carriers from a variety of bacterial sources, as well as fungal siderophore ferrichrome [14]. However, another study has shown that when pyrrolidine is added into the culture of AF, the excess iron can be utilized by AF only when pyrrolidine reaches saturation [15]. PA can use this pyrrolidine to supplement iron for its growth, but AF can’t. The enhanced utilization of siderophores leads to the advantage of PA in competitive survival.