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Brinkmann, S.

Publications and source records attributed to Brinkmann, S..

3 recordsLinked to original sources

Reduced antibiotic effect of ciprofloxacin on bacteria in the presence of montmorillonite

Antibiotic residues exceeding selective concentrations for antibiotic-resistant bacteria have been detected in various environments, including manure, wastewater, and effluents from wastewater treatment plants. When these residues come into contact with soils, for instance, due to wastewater irrigation or fertilization with manure, they interact with soil constituents. Soil colloids (1-1000 nm), such as montmorillonite, have been observed to adsorb pharmaceuticals, including antibiotics. We investigated the effect of colloids on the bioavailability of ciprofloxacin and found, that added to bacterial growth medium, montmorillonite reduces, but does not completely prevent, the growth-inhibitory effect of the antibiotic. The bacteria were able to grow at up to roughly double the concentration of ciprofloxacin in the presence of montmorillonite. We show that the incomplete deactivation of ciprofloxacin was most probably caused by medium components that decreased the adsorption of ciprofloxacin to montmorillonite. We conclude that a selective potential of this highly active antibiotic in contaminated soils, which also contain nutrients enabling bacterial growth, cannot be ruled out. Environmental implicationAntibiotics such as ciprofloxacin are frequently detected in water bodies and soils due to wastewater irrigation or manure application. These residues raise concerns about environmental toxicity and antibiotic resistance. This study demonstrates that montmorillonite, a common clay mineral in soils, significantly reduces the antimicrobial efficacy of environmental ciprofloxacin concentrations by sorption. The findings reveal a natural attenuation mechanism that may influence the environmental fate and bioavailability of antibiotics. Understanding such interactions is critical for predicting antibiotic behavior in terrestrial systems and for designing more accurate environmental risk assessments.

microbiology↗

Identification, Characterization and Synthesis of Natural Parasitic Cysteine Protease Inhibitors -- More Potent Falcitidin Analogs

Protease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was the first member of a new class of inhibitors of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum. Using a metabolomics dataset of 25 Chitinophaga strains for molecular networking enabled identification of over 30 natural analogs of falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, and C-terminal functionalization; therefore, they were grouped into the four falcitidin peptide families A-D. The isolation, characterization and absolute structure elucidation of two falcitidin-related pentapeptide aldehyde analogs by extensive MS/MS spectrometry and NMR spectroscopy in combination with advanced Marfeys analysis was in agreement with the in silico analysis of the corresponding biosynthetic gene cluster. Total synthesis of chosen pentapeptide analogs followed by in vitro testing against a panel of proteases revealed selective parasitic cysteine protease inhibition and additionally low-micromolar inhibition of -chymotrypsin. The pentapeptides investigated here showed superior inhibitory activity compared to falcitidin.

microbiology↗

Genomic and chemical decryption of the Bacteroidetes phylum for its potential to biosynthesize natural products

With progress in genome sequencing and data sharing, 1000s of bacterial genomes are publicly available. Genome mining - using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis and rating - has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of peerless strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Sourcing this dataset, we isolated the new iron chelating nonribosomally-synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida, produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively. TeaserCombination of omics-technologies revealed taxonomical hotspots for specialized metabolites within Bacteroidetes.

microbiology↗