Accurate Mass MS/MS/MS Analysis of Siderophores Ferrioxamine B and E1 by Collision-Induced Dissociation Electrospray Mass Spectrometry

Sidebottom, Ashley M.; Karty, Jonathan A.; Carlson, Erin E.

doi:10.1007/s13361-015-1242-7

Cited by 9 publications

(10 citation statements)

References 16 publications

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“…All mass spectrometry experiments were conducted using ultrapressure liquid chromatography-electrospray ionization-quad time of flight mass spectrometry (UPLC-ESI-QTOF MS) instrumentation (Agilent catalog no. 6540), as described previously (40, 41). Each extract was dissolved in 400 µl of H 2 O/acetonitrile (Fisher; LC-MS grade) (50:50), 2 µl of which were separated on a Zorbax C 18 column (Agilent) (2.1 by 50 mm, 1.8 µm pore size).…”

Section: Methodsmentioning

confidence: 99%

StreptomycesVolatile Compounds Influence Exploration and Microbial Community Dynamics by Altering Iron Availability

Jones

Pham

Zambri

et al. 2019

mBio

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Bacteria and fungi produce a wide array of volatile organic compounds (VOCs), and these can act as chemical cues or as competitive tools. Recent work has shown that the VOC trimethylamine (TMA) can promote a new form of Streptomyces growth, termed “exploration.” Here, we report that TMA also serves to alter nutrient availability in the area surrounding exploring cultures: TMA dramatically increases the environmental pH and, in doing so, reduces iron availability. This, in turn, compromises the growth of other soil bacteria and fungi. In response to this low-iron environment, Streptomyces venezuelae secretes a suite of differentially modified siderophores and upregulates genes associated with siderophore uptake. Further reducing iron levels by limiting siderophore uptake or growing cultures in the presence of iron chelators enhanced exploration. Exploration was also increased when S. venezuelae was grown in association with the related low-iron- and TMA-tolerant Amycolatopsis bacteria, due to competition for available iron. We are only beginning to appreciate the role of VOCs in natural communities. This work reveals a new role for VOCs in modulating iron levels in the environment and implies a critical role for VOCs in modulating the behavior of microbes and the makeup of their communities. It further adds a new dimension to our understanding of the interspecies interactions that influence Streptomyces exploration and highlights the importance of iron in exploration modulation. IMPORTANCE Microbial growth and community interactions are influenced by a multitude of factors. A new mode of Streptomyces growth—exploration—is promoted by interactions with the yeast Saccharomyces cerevisiae and requires the emission of trimethylamine (TMA), a pH-raising volatile compound. We show here that TMA emission also profoundly alters the environment around exploring cultures. It specifically reduces iron availability, and this in turn adversely affects the viability of surrounding microbes. Paradoxically, Streptomyces bacteria thrive in these iron-depleted niches, both rewiring their gene expression and metabolism to facilitate iron uptake and increasing their exploration rate. Growth in close proximity to other microbes adept at iron uptake also enhances exploration. Collectively, the data from this work reveal a new role for bacterial volatile compounds in modulating nutrient availability and microbial community behavior. The results further expand the repertoire of interspecies interactions and nutrient cues that impact Streptomyces exploration and provide new mechanistic insight into this unique mode of bacterial growth.

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Section: Methodsmentioning

confidence: 99%

StreptomycesVolatile Compounds Influence Exploration and Microbial Community Dynamics by Altering Iron Availability

Jones

Pham

Zambri

et al. 2019

mBio

Self Cite

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“…Whereas detailed structural analyses of DFO and FO fragmentation have been performed elsewhere, , AO has not been studied in depth. We propose a MS 2 fragmentation pattern for AO (Figure ) that explains the observed spectrum and is homologous to the previously reported fragmentation patterns for FO. , The fragmentation of nonchelated and chelated forms of a custom-synthesized deuterated deferoxamine analogue (DFO- d 7 , Medical Isotopes Inc., Pelham NH) were analyzed by a similar preparation of standard solutions ( m / z for DFO- d 7 , FO- d 7 , and AO- d 7 568.4, 621.4, and 591.5 respectively; Figure D–F). All three species for both the deuterated and nondeuterated DFO were used in further analyses and quantification.…”

Section: Results and Discussionmentioning

confidence: 65%

“…Solutions of DFO were combined with a source of either Fe(III) or Al(III) and analyzed to collect the mass spectra and fragmentation of FO ( m / z 614.3) and AO ( m / z 584.9), respectively (Figure B, C). Whereas detailed structural analyses of DFO and FO fragmentation have been performed elsewhere, , AO has not been studied in depth. We propose a MS 2 fragmentation pattern for AO (Figure ) that explains the observed spectrum and is homologous to the previously reported fragmentation patterns for FO. , The fragmentation of nonchelated and chelated forms of a custom-synthesized deuterated deferoxamine analogue (DFO- d 7 , Medical Isotopes Inc., Pelham NH) were analyzed by a similar preparation of standard solutions ( m / z for DFO- d 7 , FO- d 7 , and AO- d 7 568.4, 621.4, and 591.5 respectively; Figure D–F).…”

Section: Results and Discussionmentioning

confidence: 99%

Quantifying Intranasally Administered Deferoxamine in Rat Brain Tissue with Mass Spectrometry

Kosyakovsky

Witthuhn

Svitak

et al. 2019

ACS Chem. Neurosci.

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Deferoxamine, a metal chelator, has been shown to be neuroprotective in animal models of ischemic stroke, traumatic brain injury and both subarachnoid and intracerebral hemorrhage. Intranasal deferoxamine (IN DFO) has also shown promise as a potential treatment for multiple neurodegenerative diseases, including Parkinson’s and Alzheimer’s. However, there have been no attempts to thoroughly understand the dynamics and pharmacokinetics of IN DFO. We developed a new high-performance liquid-chromatography electrospray-tandem mass spectrometry (HPLC/ESI-MS2) method to quantify the combined total levels of DFO, ferrioxamine (FO; DFO bound to iron), and aluminoxamine (AO; aluminum-bound DFO) in brain tissue using a custom-synthesized deuterated analogue (DFO-d 7, Medical Isotopes Inc., Pelham NH) as an internal standard. We applied our method toward understanding the pharmacokinetics of IN DFO delivery to the brain and blood of rats from 15 min to 4 h after delivery. We found that IN delivery successfully targets DFO to the brain to achieve concentrations of 0.5–15 μM in various brain regions within 15 min, and decreasing though still detectable after 4 h. Systemic exposure was minimized as assessed by concentration in blood serum. Serum concentrations were 0.02 μM at 15 min and no more than 0.1 μM at later time points. Compared to blood serum, brain region-specific drug exposure (as measured by area under the curve) ranged from slightly under 10 times exposure in the hippocampus to almost 200 times exposure in the olfactory bulb with IN DFO delivery. These findings represent a major step toward future method development, pharmacokinetic studies, and clinical trials for this promising therapeutic.

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“…Full scan chromatograms were searched against an m / z list of known desferrioxiamines and ferrioxiamines published in literature [ 66 , 67 ]. A maximal difference from the theoretical mass of 5 ppm was set for this search.…”

Section: Methodsmentioning

confidence: 99%

The Genome Analysis of the Human Lung-Associated Streptomyces sp. TR1341 Revealed the Presence of Beneficial Genes for Opportunistic Colonization of Human Tissues

et al. 2021

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Streptomyces sp. TR1341 was isolated from the sputum of a man with a history of lung and kidney tuberculosis, recurrent respiratory infections, and COPD. It produces secondary metabolites associated with cytotoxicity and immune response modulation. In this study, we complement our previous results by identifying the genetic features associated with the production of these secondary metabolites and other characteristics that could benefit the strain during its colonization of human tissues (virulence factors, modification of the host immune response, or the production of siderophores). We performed a comparative phylogenetic analysis to identify the genetic features that are shared by environmental isolates and human respiratory pathogens. The results showed a high genomic similarity of Streptomyces sp. TR1341 to the plant-associated Streptomyces sp. endophyte_N2, inferring a soil origin of the strain. Putative virulence genes, such as mammalian cell entry (mce) genes were not detected in the TR1341’s genome. The presence of a type VII secretion system, distinct from the ones found in Mycobacterium species, suggests a different colonization strategy than the one used by other actinomycete lung pathogens. We identified a higher diversity of genes related to iron acquisition and demonstrated that the strain produces ferrioxamine B in vitro. These results indicate that TR1341 may have an advantage in colonizing environments that are low in iron, such as human tissue.

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Accurate Mass MS/MS/MS Analysis of Siderophores Ferrioxamine B and E1 by Collision-Induced Dissociation Electrospray Mass Spectrometry

Cited by 9 publications

References 16 publications

StreptomycesVolatile Compounds Influence Exploration and Microbial Community Dynamics by Altering Iron Availability

StreptomycesVolatile Compounds Influence Exploration and Microbial Community Dynamics by Altering Iron Availability

Quantifying Intranasally Administered Deferoxamine in Rat Brain Tissue with Mass Spectrometry

The Genome Analysis of the Human Lung-Associated Streptomyces sp. TR1341 Revealed the Presence of Beneficial Genes for Opportunistic Colonization of Human Tissues

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