Siderophore natural products as pharmaceutical agents

Swayambhu, Girish; Bruno, Michael J.; Gulick, Andrew M.; Pfeifer, Blaine A.

doi:10.1016/j.copbio.2021.01.021

Cited by 36 publications

(18 citation statements)

References 77 publications

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“…Petrobactin is a low-molecular-mass iron (3)-chelating compound. Siderophore antibiotic conjugate is an approach to overcome cellular barriers; in the case of petrobactin, it is essential for iron uptake in bacteria, in which a petrobactin antibiotic conjugate can act as a Trojan horse for the antibacterial activity [ 35 , 36 ]. Tridecaptin showed its potential against Gram-negative bacteria with low cytotoxicity as it blocks ATP synthesis in bacteria through a lipid-II-binding motif [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Nature of the Antimicrobial Metabolites Produced by Paenibacillus ehimensis Soil Isolate MZ921932 Using a Metagenomic Nanopore Sequencing Coupled with LC-Mass Analysis

Eltokhy

Saad²,

Eltayeb

et al. 2021

Antibiotics

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The continuous emergence of multidrug-resistant (MDR) pathogens poses a global threat to public health. Accordingly, global efforts are continuously conducted to find new approaches to infection control by rapidly discovering antibiotics, particularly those that retain activities against MDR pathogens. In this study, metagenomic nanopore sequence analysis coupled with spectroscopic methods has been conducted for rapid exploring of the various active metabolites produced by Paenibacillus ehimensis soil isolate. Preliminary soil screening resulted in selection of a Gram-positive isolate identified via 16S ribosomal RNA gene sequencing as Paenibacillus ehimensis MZ921932. The isolate showed a broad range of activity against MDR Gram-positive, Gram-negative, and Candida spp. A metagenomics sequence analysis of the soil sample harboring Paenibacillus ehimensis isolate MZ921932 (NCBI GenBank accession PRJNA785410) revealed the presence of conserved biosynthetic gene clusters of petrobactin, tridecaptin, locillomycin (β-lactone), polymyxin, and macrobrevin (polyketides). The liquid chromatography/mass (LC/MS) analysis of the Paenibacillus ehimensis metabolites confirmed the presence of petrobactin, locillomycin, and macrobrevin. In conclusion, Paenibacillus ehimensis isolate MZ921932 is a promising rich source for broad spectrum antimicrobial metabolites. The metagenomic nanopore sequence analysis was a rapid, easy, and efficient method for the preliminary detection of the nature of the expected active metabolites. LC/MS spectral analysis was employed for further confirmation of the nature of the respective active metabolites.

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Section: Discussionmentioning

confidence: 99%

Exploring the Nature of the Antimicrobial Metabolites Produced by Paenibacillus ehimensis Soil Isolate MZ921932 Using a Metagenomic Nanopore Sequencing Coupled with LC-Mass Analysis

Eltokhy

Saad²,

Eltayeb

et al. 2021

Antibiotics

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“…In terms of clinical indexes, the urine WBC/HP level of the OA1 cluster was much higher than the OA2 cluster, which may be due to the differential relative abundance of Enterobacteriaceae in OA1 and OA2 clusters. From the perspective of metabolic pathways, Enterobacteriaceae was closely related to Bacterial invasion of epithelial cells (rho = 0.73) and Biosynthesis of siderophore group nonribosomal peptides (rho = 0.64), while these two pathways are considered related to UTI ( Amalaradjou et al., 2011 ; Swayambhu et al., 2021 ). These pathways were negatively correlated with bacteria that had higher abundance in the OA2 cluster compared with the OA1 cluster (such as Enterococcus , Staphylococcus , and Acinetobacter ).…”

Section: Discussionmentioning

confidence: 99%

Identifying Two Novel Clusters in Calcium Oxalate Stones With Urinary Tract Infection Using 16S rDNA Sequencing

Shen

Zhu

Fan

et al. 2021

Front. Cell. Infect. Microbiol.

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Urinary stones and urinary tract infection (UTI) are the most common diseases in urology and they are characterized by high incidence and high recurrence rate in China. Previous studies have shown that urinary stones are closely associated with gut or urine microbiota. Calcium oxalate stones are the most common type of urinary stones. However, the profile of urinary tract microorganisms of calcium oxalate stones with UTI is not clear. In this research, we firstly found two novel clusters in patients with calcium oxalate stones (OA) that were associated with the WBC/HP (white blood cells per high-power field) level in urine. Two clusters in the OA group (OA1 and OA2) were distinguished by the key microbiota Firmicutes and Enterobacteriaceae. We found that Enterobacteriaceae enriched in OA1 cluster was positively correlated with several infection-related pathways and negatively correlated with a few antibiotics-related pathways. Meantime, some probiotics with higher abundance in OA2 cluster such as Bifidobacterium were positively correlated with antibiotics-related pathways, and some common pathogens with higher abundance in OA2 cluster such as Enterococcus were positively correlated with infection-related pathways. Therefore, we speculated that as a sub-type of OA disease, OA1 was caused by Enterobacteriaceae and the lack of probiotics compared with OA2 cluster. Moreover, we also sequenced urine samples of healthy individuals (CK), patients with UTI (I), patients with uric acid stones (UA), and patients with infection stones (IS). We identified the differentially abundant taxa among all groups. We hope the findings will be helpful for clinical treatment and diagnosis of urinary stones.

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“…Siderophores primarily bind iron, but they also can bind other metals based on their major structural group (118). P. aeruginosa produces two major siderophores, PVD and pyochelin, which form complexes with Fe 3+ , Ag + , Al 3+ , Cd 2+ , Co 2+ , Cr 2+ , Cu 2+ , Eu 3+ , Ga 3+ , Hg 2+ , Mn 2+ , Ni 2+ , Pb 2+ , Sn 2+ , Tb 3+ , Tl + , and Zn 2+ , although many of these metals are not efficiently transported into the cell (119,120).…”

Section: Metal Sequestration By Siderophoresmentioning

confidence: 99%

“…Sideromycins are generated by linking a siderophore to an antibiotic component, although naturally occurring sideromycins are limited (2,13,137). A number of sideromycins have been synthesized to use as therapeutics against bacterial infections due to their targeted antimicrobial activity (10,118,137). Burkholderia thailandensis produces the natural sideromycin malleonitrone (138), which exhibits antibiotic activity against Gram-negative bacteria and inhibits P. aeruginosa (138).…”

Section: Antibiotic Activity Of Siderophoresmentioning

confidence: 99%

Understanding the Potential and Risk of Bacterial Siderophores in Cancer

et al. 2022

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Siderophores are iron chelating molecules produced by nearly all organisms, most notably by bacteria, to efficiently sequester the limited iron that is available in the environment. Siderophores are an essential component of mammalian iron homeostasis and the ongoing interspecies competition for iron. Bacteria produce a broad repertoire of siderophores with a canonical role in iron chelation and the capacity to perform versatile functions such as interacting with other microbes and the host immune system. Siderophores are a vast area of untapped potential in the field of cancer research because cancer cells demand increased iron concentrations to sustain rapid proliferation. Studies investigating siderophores as therapeutics in cancer generally focused on the role of a few siderophores as iron chelators; however, these studies are limited and some show conflicting results. Moreover, siderophores are biologically conserved, structurally diverse molecules that perform additional functions related to iron chelation. Siderophores also have a role in inflammation due to their iron acquisition and chelation properties. These diverse functions may contribute to both risks and benefits as therapeutic agents in cancer. The potential of siderophore-mediated iron and bacterial modulation to be used in the treatment of cancer warrants further investigation. This review discusses the wide range of bacterial siderophore functions and their utilization in cancer treatment to further expand their functional relevance in cancer detection and treatment.

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Siderophore natural products as pharmaceutical agents

Cited by 36 publications

References 77 publications

Exploring the Nature of the Antimicrobial Metabolites Produced by Paenibacillus ehimensis Soil Isolate MZ921932 Using a Metagenomic Nanopore Sequencing Coupled with LC-Mass Analysis

Exploring the Nature of the Antimicrobial Metabolites Produced by Paenibacillus ehimensis Soil Isolate MZ921932 Using a Metagenomic Nanopore Sequencing Coupled with LC-Mass Analysis

Identifying Two Novel Clusters in Calcium Oxalate Stones With Urinary Tract Infection Using 16S rDNA Sequencing

Understanding the Potential and Risk of Bacterial Siderophores in Cancer

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