Siderophores in Iron Metabolism: From Mechanism to Therapy Potential

Abstract

Iron is an essential nutrient for life. During infection, a fierce battle of iron acquisition occurs between the host and bacterial pathogens. Bacteria acquire iron by secreting siderophores, small ferric iron binding molecules. In response, host immune cells secrete lipocalin 2 (also known as siderocalin), a siderophore-binding protein, to prevent bacterial reuptake of iron-loaded siderophores. To counter this threat, some bacteria can produce lipocalin 2-resistant siderophores. This review discusses the recently described molecular mechanisms of siderophore iron trafficking between host and bacteria, highlighting the therapeutic potential of exploiting pathogen siderophore machinery for the treatment of antibiotic-resistant bacterial infections. As the latter reflect a persistent problem in hospital settings, siderophore-targeting or siderophore-based compounds represent a promising avenue to combat such infections.

Control of metabolite efflux in microbial cell factories: current advances and future prospects

“…Depending on the pH, an equilibrative transporter may be sufficient [150]. Siderophores are of course another well-known class of compounds excreted by plants and microbes to assist their uptake of iron [151][152][153][154]. Dicarboxylate efflux transporters are also known [155], potentially (and experimentally) serving similar purposes [148,156].…”

Медикаментозне Обмеження Доступності Іонів Заліза Для Патогенних Бактерій (Частина 1)

“…Поглощение сидерофоров грамотрицательными [13]. Секрецию сидерофоров осуществляют эф-флюксные насосы таких молекулярных семейств, как главного фасилитатора (major facilitator superfamily -MFS) и специфической группы протеи-нов резистентности грамотрицательной флоры (Gram-negative-specific Resistance-Nodulation-Cell Division -RND) [49].…”

El género Bacillus como agente de control biológico y sus implicaciones en la bioseguridad agrícola

“…This allows for the formation of Fe 3+ -siderophore complexes, so siderophore-producing microorganisms, using a specific receptor located in the membrane, can use it using two mechanisms: 1) directly with the Fe 3+ -siderophore complex through the cell membrane, or 2) reducing extracellularly to Fe 2+ complexes (Neilands, 1995) (Figure 6-A). Siderophores, based on their main chelating group, are classified into: hydroxamates (using hydroxamic acids), catecholates (containing catechol rings), carboxylates, phenolates, and in a combination of two or more of these groups (Wilson et al, 2016) (Figure 6-B). A wide diversity of strains with the capacity of biological control belonging to the Bacillus genus have shown the ability to synthesize siderophores, regulating the concentration of iron in the medium through its chelation (Fe 3+ -siderophore), causing this metal to become unavailable for pathogenic microorganisms, which depend highly on this element for growth (Scharf et al, 2014).…”

“…Lo cual permite la formación de complejos Fe 3+ -sideróforo, así los microorganismos productores de sideróforos, mediante un receptor especí-fico localizado en la membrana, pueden utilizarlo por dos mecanismos: 1) directamente mediante el complejo Fe 3+ -sideróforo a través de la membrana celular, o 2) reducido extracelularmente a complejos Fe 2+ (Neilands, 1995) (Figura 6-A). Los sideróforos en función de su principal grupo quelante se clasifican en: hidroxamatos (utilizando ácidos hidroxámicos), catecolatos (conteniendo anillos catecol), carboxilatos, fenolatos, y en combinación de dos o más de estos grupos (Wilson et al, 2016) (Figura 6-B). Una amplia diversidad de cepas con capacidad de control biológico pertenecientes al género Bacillus han mostrado la capacidad de sintetizar sideróforos, regulando la concentración de hierro en el medio a través de su quelación (Fe 3+ -sideróforo), ocasionando que este metal no se encuentre disponible para microorganismos patóge-nos, cuyo crecimiento es altamente dependiente de este elemento (Scharf et al, 2014).…”