Siderophore–drug complexes: potential medicinal applications of the ‘Trojan horse’ strategy

Górska, Agnieszka; Sloderbach, Anna; Marszałł, Michał Piotr

doi:10.1016/j.tips.2014.06.007

Cited by 144 publications

(123 citation statements)

References 56 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…Figure 5 shows the diagram of the formation of Trojan horse complex. The siderophoredrug complex selectively interacts with the siderophore receptors on the bacterial cell surface and is then actively transported across the outer membrane (Gorska et al 2014).…”

Section: Trojan Horse Antibioticsmentioning

confidence: 99%

“…However, nanotechnology has emerged as a new field offering new possibilities in designing efficient therapeutic systems that enable more precise delivery of drugs to the appropriate site of action. The development of iron oxide nanoparticle based therapeutic systems can facilitate more precise delivery of drug to the appropriate location (Gorska et al 2014). …”

Section: Trojan Horse Antibioticsmentioning

confidence: 99%

See 1 more Smart Citation

Microbial siderophores and their potential applications: a review

Saha

Sarkar

et al. 2015

Environ Sci Pollut Res

597

278

View full text Add to dashboard Cite

Siderophores are small organic molecules produced by microorganisms under iron-limiting conditions which enhance the uptake of iron to the microorganisms. In environment, the ferric form of iron is insoluble and inaccessible at physiological pH (7.35-7.40). Under this condition, microorganisms synthesize siderophores which have high affinity for ferric iron. These ferric iron-siderophore complexes are then transported to cytosol. In cytosol, the ferric iron gets reduced into ferrous iron and becomes accessible to microorganism. In recent times, siderophores have drawn much attention due to its potential roles in different fields. Siderophores have application in microbial ecology to enhance the growth of several unculturable microorganisms and can alter the microbial communities. In the field of agriculture, different types of siderophores promote the growth of several plant species and increase their yield by enhancing the Fe uptake to plants. Siderophores acts as a potential biocontrol agent against harmful phyto-pathogens and holds the ability to substitute hazardous pesticides. Heavy-metal-contaminated samples can be detoxified by applying siderophores, which explicate its role in bioremediation. Siderophores can detect the iron content in different environments, exhibiting its role as a biosensor. In the medical field, siderophore uses the "Trojan horse strategy" to form complexes with antibiotics and helps in the selective delivery of antibiotics to the antibiotic-resistant bacteria. Certain iron overload diseases for example sickle cell anemia can be treated with the help of siderophores. Other medical applications of siderophores include antimalarial activity, removal of transuranic elements from the body, and anticancer activity. The aim of this review is to discuss the important roles and applications of siderophores in different sectors including ecology, agriculture, bioremediation, biosensor, and medicine.

show abstract

Section: Trojan Horse Antibioticsmentioning

confidence: 99%

Section: Trojan Horse Antibioticsmentioning

confidence: 99%

Microbial siderophores and their potential applications: a review

Saha

Sarkar

et al. 2015

Environ Sci Pollut Res

597

278

View full text Add to dashboard Cite

show abstract

“…Over the past three decades, numerous conjugates linking a siderophore or a siderophore mimic to different antibiotics via a linker molecule have been synthesized with varying degrees of antimicrobial efficacy (Möllmann et al, 2009;Wencewicz et al, 2009;Zeng et al, 2012;Fardeau et al, 2014). This approach, known as the 'Trojan horse' strategy, has been the subject of several reviews (including those by de Carvalho & Fernandes, 2014;Gó rska et al, 2014;Mislin & Schalk, 2014). Challenges to the design of these conjugates include optimal linker design to avoid interference with siderophore receptor binding and the development of resistance due to the loss of components of the siderophore uptake system (Minnick et al, 1992).…”

Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

View full text Add to dashboard Cite

Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

show abstract

“…In a previous work we predicted a cluster of genes encoding all enzymes necessary for siderophore biosynthesis and transport (Pulgar et al, 2015). Siderophores have the potential to be modified in order to improve the delivery of antibiotics by using them as Trojan horses, a biotechnological approach that have been employed to counter bacterial antibiotic resistance (Gorska et al, 2014). In addition to the iron acquisition genes, the genome of P. salmonis contains other 143 putative virulence genes that were identified by blastp search against VFDB (Chen et al, 2012).…”

Section: Farmingmentioning

confidence: 99%