Mass Spectrometric Analysis of Drug-induced Changes in Na+ and K+ Contents of Single Bacterial Cells

Lindner, Buko; Seydel, Ulrich

doi:10.1099/00221287-129-1-51

Cited by 6 publications

(6 citation statements)

References 6 publications

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“…Details of the technique and the mass spectrometric determination of viability have been described previously (36). For cultivable bacteria, we showed that the physiological states (viabilities) determined by mass spectrometric analysis of the cation ratios agreed well with those determined by established microbiological techniques (17,30,37) and, in the case of M. lepraemurium, with those determined by the mouse footpad assay (13).…”

supporting

confidence: 64%

“…The mass spectrometric analysis of intrabacterial Na ϩ -to-K ϩ ratios of individual bacterial organisms is routinely used in our laboratory to monitor the effects of drugs on bacterial viability (10,12,13,17,29,30,36,37). Since this method renders information independent from the ability of the bacterial organisms to multiply in vitro, it saves time and labor in the case of slowly growing cultivable mycobacteria and, moreover, can also be used in the case of the noncultivable species M. leprae.…”

Section: Discussionmentioning

confidence: 99%

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Drug effects on intracellular mycobacteria determined by mass spectrometric analysis of the Na(+)-to-K+ ratios of individual bacterial organisms

Wiese

Seydel

1996

Antimicrob Agents Chemother

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The successful establishment of a drug screening system for intracellular cultivable and noncultivable mycobacteria based on the mass spectrometric determination of bacterial viability is described. To compare drug efficacies on intra- and extracellular mycobacteria, the mycobacteria were subjected to drug treatment either after phagocytosis by the mouse macrophage cell line RAW 264.7 or in cell-free medium. After reisolation, their viability was monitored by analyzing the intrabacterial sodium-to-potassium ratios for a limited number of individual organisms. This approach offers a reliable and quick tool for monitoring the influence of intracellular growth and of additional permeation barriers on intracellular drug efficacy and will thus provide useful information for the rational development and testing of optimized antimycobacterial drugs. In particular, the methodology is applicable to the noncultivable species Mycobacterium leprae, because the mass spectrometric analysis of the intrabacterial sodium-to-potassium ratio allows the determination of bacterial viability independent from their ability to multiply in vitro. Because of the improved metabolic activity of intracellularly growing M. leprae compared with that of extracellularly growing M. leprae, the spectrum of antileprosy drugs that can be tested in vitro could even be extended to those interfering with DNA replication and cell division.

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supporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Drug effects on intracellular mycobacteria determined by mass spectrometric analysis of the Na(+)-to-K+ ratios of individual bacterial organisms

Wiese

Seydel

1996

Antimicrob Agents Chemother

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“…At the beginning of SCMS in the late 1970s, laser ablation (LA) was used to produce ionic species from tissues and cell cultures [5]. In 1981, LA‐MS was used to determine the physiological state of individual bacterial cells by analyzing sodium/potassium concentration ratios [6, 7]. The LA‐MS instrument was a laser microprobe mass analyzer (LAMMA 500), developed by F. Hillenkamp and M. Karas, who were the first to report MALDI in 1988 [8].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic device integrating single‐cell extraction and electrical lysis for mass spectrometry detection of intracellular compounds

Václavek

Foret

2022

Electrophoresis

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Analysis of cellular composition and metabolism at a single‐cell resolution allows gaining more information about complex relationships of cells within tissues or whole living organisms by resolving the variance stemming from the cellular heterogeneity. Mass spectrometry (MS) is a perfect analytical tool satisfying the demanding requirements of detecting and identifying compounds present in such ultralow‐volume samples of high chemical complexity. However, the method of sampling and sample ionization is crucial in obtaining relevant information. In this work, we present a microfluidic sampling platform that integrates single‐cell extraction from MS‐incompatible media with electrical cell lysis and nanoESI‐MS analysis of human erythrocytes. Hemoglobin alpha and beta chains (300 amol/cell) were successfully identified in mass spectra of single‐erythrocyte lysates.

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“…Hepatotoxicity implies chemical-driven liver damage and it is the most common reason for a drug to be withdrawn from the market with more than 900 drugs implicated in causing liver injury [23]. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for drug screening assays, such as stemp cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process [18]. Hepatotoxicity data were used to build a number of QSTR models to identify the structural features of compounds correlated to their hepatotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Structure-Hepatotoxicity Assessment of Series Arylpiperazine-N1-Substituted Theobromine Derivatives

Kondeva-Burdina¹

2020

FARMACIA

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In this work series new theobromine derivatives containing an arylpiperazine moiety at N 1 with established antioxidant and antiproliferative activities were evaluated for their hepatotoxic effects on cellular and sub-cellular level. On isolated rat hepatocytes, 3c and 4c expressed lowest toxicity, while 3f and 4f showed highest toxicity. The same compounds 3f and 4f showed the most evident pro-oxidant effect in a lipid peroxidation model on rat liver microsomes, followed by 3b and 4b, while the other compounds didn't reveal statistically significant pro-oxidant effects. The performed quantitative structuretoxicity relationship (QSTR) analysis show that increased lipophilicity of the tested compounds positively correlates to their hepatotoxicity. Opposite, the presence in the structure of highly positive H-atoms and strongly negative oxygen, possibly originating from hydrogen bond donor groups, are associated with reduced hepatotoxicity. RezumatÎn această lucrare, noi derivați de teobromină care conțin o grupare arilpiperazină la N 1 cu activități antioxidante și antiproliferative consacrate, au fost evaluați pentru efectele lor hepatotoxice la nivel celular și subcelular. Asupra hepatocitelor izolate de șobolan, 3c și 4c au exprimat cea mai mică toxicitate, în timp ce 3f și 4f au prezentat cea mai mare toxicitate. Aceiași compuși 3f și 4f au arătat cel mai evident efect pro-oxidant într-un model de peroxidare lipidică asupra microzomilor hepatici proveniți de la șobolan, urmați de 3b și 4b, în timp ce ceilalți compuși nu au arătat efecte pro-oxidante semnificative statistic. Analiza cantitativă a relației structură-toxicitate (QSTR) a arătat că lipofilia crescută a compușilor testați se corelează pozitiv cu hepatotoxicitatea lor. În mod contrar, prezența în structură a atomilor de H foarte pozitivi și a celor de oxigen puternic negativi, este asociată cu o hepatotoxicitate redusă.

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Mass Spectrometric Analysis of Drug-induced Changes in Na+ and K+ Contents of Single Bacterial Cells

Cited by 6 publications

References 6 publications

Drug effects on intracellular mycobacteria determined by mass spectrometric analysis of the Na(+)-to-K+ ratios of individual bacterial organisms

Drug effects on intracellular mycobacteria determined by mass spectrometric analysis of the Na(+)-to-K+ ratios of individual bacterial organisms

Microfluidic device integrating single‐cell extraction and electrical lysis for mass spectrometry detection of intracellular compounds

Quantitative Structure-Hepatotoxicity Assessment of Series Arylpiperazine-N1-Substituted Theobromine Derivatives

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