Biology subjects

Bartel, J.

Publications and source records attributed to Bartel, J..

4 recordsLinked to original sources

bioRxiv2026

Pathogen-driven reactivation of metabolite prodrugs defines nitroxoline's iron-deprivation antibiotic activity

The rise of antimicrobial resistance warrants renewed attention to established but overlooked antibiotics such as nitroxoline (NTX). Here, we systematically dissect NTXs mode of action and investigate the contribution of its first-pass metabolites, NTX-sulphate and NTX-glucuronide. We identified metallophore-mediated cellular iron deprivation as the principal antibacterial mechanism of NTX, characterized by induction of iron acquisition pathways and Fe-S cluster proteins, and concomitant loss of protein-bound iron. In contrast, NTX metabolites were biologically inactive and lacked metal-chelating properties. Ex vivo assays demonstrated that clinically relevant uropathogens, including Escherichia coli and Klebsiella pneumoniae, efficiently reconvert these metabolites into active NTX in human urine. Together, our findings establish a mechanistic framework linking NTX antibacterial activity, host detoxification, and pathogen-dependent metabolite reactivation, and providing a molecular explanation for NTXs enduring therapeutic potential and favourable safety profile.

microbiology↗

bioRxiv2024

RAPDOR: Using Jensen-Shannon Distance for the computational analysis of complex proteomics datasets

The computational analysis of large proteomics datasets, such as those from gradient profiling or spatially resolved proteomics, is often as crucial as the experimental design. We present RAPDOR, a tool for intuitive analyzing and visualizing such datasets, based on the Jensen-Shannon distance and subsequent analysis of similarities between replicates, applied to three datasets. First, we examined the in-gradient distribution profiles of protein complexes with or without RNase treatment (GradR) to identify the set of RNA-binding proteins (RBPs) in the cyanobacterium Synechocystis sp. PCC 6803. RBPs play pivotal regulatory and structural roles; although numerous RBPs have been identified, the complete set is unknown for any species. RAPDOR identified 80 potential RBPs, including ribosomal proteins, likely RNA-modifying enzymes, and several proteins not previously associated with RNA binding. High-ranking putative RBPs, such as the universal stress protein Sll1388, or the translation inhibitor LrtA/RaiA, were predicted by RAPDOR but not the TriPepSVM algorithm, indicating uncharacterized RBP domains. These data are available online at https://synecho-rapdor.biologie.uni-freiburg.de, providing a comprehensive resource for RNase-sensitive protein complexes in cyanobacteria. We then show by reanalyzing existing datasets, that RAPDOR is effective in examining the intracellular redistribution of proteins under stress conditions. RAPDOR is a generic, non-parametric tool for the intuitive and versatile analysis of highly complex data sets such as the study of protein distributions using fractionation protocols.

bioinformatics↗

bioRxiv2021

CdrS is a global transcriptional regulator influencing cell division in Haloferax volcanii

Transcriptional regulators that integrate cellular and environmental signals to control cell division are well known in bacteria and eukaryotes, but their existence is poorly understood in archaea. We identified a conserved gene (cdrS) that encodes a small protein and is highly transcribed in the model archaeon Haloferax volcanii. The cdrS gene could not be deleted, but CRISPRi-mediated repression of the cdrS gene caused slow growth, cell division defects, and changed the expression of multiple genes and their products associated with cell division, protein degradation and metabolism. Consistent with this complex regulatory network, overexpression of cdrS inhibited cell division, whereas overexpression of the operon encoding both CdrS and a tubulin-like cell division protein (FtsZ2) stimulated division. ChIP-Seq identified 18 DNA-binding sites of the CdrS protein including one upstream of the promoter for diadenylate cyclase, which is an essential gene involved in c-di-AMP signalling implicated in the regulation of cell division. These findings suggest that CdrS is a transcription factor that plays a central role in a regulatory network coordinating metabolism and cell division. ImportanceCell division is a central mechanism of life, and is essential for growth and development. Bacteria and Eukarya have different mechanisms for cell division, which have been studied in detail. In contrast, cell division in Archaea is still understudied, and its regulation is poorly understood. Interestingly, different cell division machineries appear in the Archaea, with the Euryarchaeota using a cell division apparatus based on the tubulin-like cytoskeletal protein FtsZ, as in bacteria. Here we identify the small protein CdrS as essential for survival and a central regulator of cell division in the Euryarchaeon Haloferax volcanii. CdrS also appears to coordinate other cellular pathways including synthesis of signalling molecules and protein degradation. Our results show that CdrS plays a sophisticated role in cell division, including regulation of numerous associated genes. These findings are expected to initiate investigations into conditional regulation of division in archaea.

microbiology↗

bioRxiv2021

A small RNA is linking CRISPR-Cas and zinc transport

The function and mode of action of small regulatory RNAs is currently still understudied in archaea. In the halophilic archaeon H. volcanii a plethora of sRNAs have been identified, however, in-depth functional analysis is missing for most of them. We selected a small RNA (s479) from H. volcanii for detailed characterization. The sRNA gene is encoded between a CRISPR RNA locus and the Cas protein gene cluster, the s479 deletion strain is viable and was characterized in detail. Transcriptome studies of wild type Haloferax cells and the deletion mutant revealed up-regulation of six genes in the deletion strain, showing that the sRNA has a clearly defined function. Three of the six up-regulated genes encode potential zinc transporter proteins (ZnuA1, ZnuB1, ZnuC1) suggesting involvement of s479 in regulation of zinc transport. Upregulation of these genes in the deletion strain was confirmed by northern blot and proteome analyses. Furthermore, electrophoretic mobility shift assays demonstrate a direct interaction of s479 with the target znuC1 mRNA. Proteome comparison of wild type and deletion strains further expanded the regulon of s479 deeply rooting this sRNA within the metabolism of H. volcanii especially the regulation of transporter abundance. Interestingly, s479 is not only encoded next to CRISPR-cas genes but the mature s479 contains a crRNA-like 5 handle and experiments with Cas protein deletion strains indicate maturation by Cas6 and interaction with Cas proteins. Together this might suggest that the CRISPR-Cas system is involved in s479 function.

molecular biology↗