Biology subjects

Globisch, D.

Publications and source records attributed to Globisch, D..

6 recordsLinked to original sources

bioRxiv2026

Multi-omics uncovers interaction in the vaginal microbiome and a type II secretion/Tad pilus system in Gardnerella vaginalis

The vaginal microbiome is a critical determinant of womens health. We investigated the genetic basis of common vaginal microbiome species and their biofilm formation. Genomic analysis of Gardnerella vaginalis (Gv) revealed a fundamental phylogenetic split correlating with high- versus low-biofilm phenotypes, driven by clade-specific genomic islands and allelic variants. In a dual-species coculture model of five key vaginal bacteria, Gv achieved numerical dominance, triggering extensive, asymmetric proteomic reprogramming in partner species while showing limited shifts itself. Proteins from biofilm-associated modules showed functional divergence, supported by AI-predicted structural variations in a type II secretion/Tad pilus system, which is first discovered from Gv strains. Integrated metabolomics identified a methyl-{beta}-carboline compound that is elevated in cocultures containing Prevotella bivia (Pb). This compound acts as a potent and selective inhibitor of Gv and Pb biofilms, sparing Lactobacillus crispatus. This work establishes a direct genomic basis for Gv virulence and demonstrates how interspecies interactions govern community dynamics and antimicrobial metabolite production. HighlightsO_LIComprehensive genomic resource comparing with high-quality long-read whole genomes and reference Gardnerella vaginalis and Lactobacillus iners strains. C_LIO_LIIntegrated multi-omics and functional analysis on the most common vaginal microbiome species using 16S rRNA gene sequencing, proteomics, metabolomics, and in vitro assays. C_LIO_LIKey phenotypes quantified, including biofilm formation and polymicrobial interactions. C_LIO_LIConserved Type II Secretion/Tad Pilus System identified across all Gardnerella vaginalis strains, with AI-predicted structural modeling. C_LIO_LIEvaluation of growth inhibition using metabolites against a panel of relevant microbes, including vaginal microbes and opportunistic pathogens. C_LI

microbiology↗

bioRxiv2026

Dual Screen for Gut Metabolites Suppressing Enterobacterial Growth and Invasiveness Reveals Structure - Activity Relationships among Anti-Infective Indoles

The antibiotic resistance crisis makes characterization of new anti-infective molecules a pressing matter. Molecules that suppress bacterial growth and survival, virulence, or the combination of these traits, all warrant further exploration. Naturally occurring microbe-host ecosystems, such as the human gut, provide incompletely tapped resources in this regard. We developed a flexible platform to parallelly assess how gut metabolites affect the growth and epithelial cell invasion capacity of the enteropathogens Salmonella enterica Typhimurium (Salmonella) and Shigella flexneri. By screening a gut metabolite library, the assays identified multiple anti-infective compound classes and extended previously reported antibacterial activities for e.g. medium chain fatty acids, bile acids, purine nucleotides, and indole. Importantly, a targeted follow-up screen combined with chemical biology iterations showed how the anti-infective activity of indole is impacted by its derivatization. Specifically, a methyl group at either of the carbons of the indole scaffold potentiated the suppressive effect on type-III-secretion-system-mediated virulence, flagellar motility (for Salmonella), and growth, in a concentration-dependent manner. By contrast, N1-methylation markedly attenuated the activity of indole and its C-derivatized versions. The study, hence, offers assays for dual growth and virulence analysis of invasive enterobacteria exposed to anti-infective candidate molecules, and informs on structure-activity relationships among indole metabolites.

microbiology↗

bioRxiv2022

A Universal Language for Finding Mass Spectrometry Data Patterns

Even though raw mass spectrometry data is information rich, the vast majority of the data is underutilized. The ability to interrogate these rich datasets is handicapped by the limited capability and flexibility of existing software. We introduce the Mass Spec Query Language (MassQL) that addresses these issues by enabling an expressive set of mass spectrometry patterns to be queried directly from raw data. MassQL is an open-source mass spectrometry query language for flexible and mass spectrometer manufacturer-independent mining of MS data. We envision the flexibility, scalability, and ease of use of MassQL will empower the mass spectrometry community to take fuller advantage of their mass spectrometry data and accelerate discoveries.

bioinformatics↗

bioRxiv2022

A broad, exposome-type evaluation of xenobiotic phase II biotransformation in human biofluids by LC-MS/MS

Xenobiotics are chemicals foreign to a specific organism that humans are exposed to on a daily basis through their food, drugs and the environment. These molecules are frequently metabolized to increase polarity and subsequent excretion. During sample preparation, deconjugation of phase II metabolites is a critical step to capture the total exposure to chemicals in liquid chromatography mass spectrometry assays (LC-MS). Knowledge on deconjugation efficiencies of different enzymes and the extend of conjugation in human biofluids has primarily been investigated for single compounds or individual chemical classes. In this study, the performance of three {beta}-glucuronidase and arylsulfatase mixtures from H. pomatia, from recombinant sources (BGS), and from Escherichia coli combined with recombinant arylsulfatase (ASPC) was compared and the efficiency of phase II deconjugation was monitored in breast milk, urine and plasma. An innovative LC-MS/MS biomonitoring method encompassing more than 80 highly diverse xenobiotics (e.g., plasticizers, industrial chemicals, mycotoxins, phytoestrogens, pesticides) was utilized for the comprehensive investigation of phase II conjugation in experiments investigating levels in breast milk and urine obtained from breastfeeding women. Overall, it was confirmed that H. pomatia is the most efficient enzyme in hydrolyzing different classes of xenobiotics for future exposome-scale biomonitoring studies. The recombinant BGS formulation, however, provided better results for breast milk samples, primarily due to lower background contamination, a major issue when employing the typically applied crude H. pomatia extracts. A deeper understanding of the global xenobiotic conjugation patterns will be essential for capturing environmental and food-related exposures within the exposome framework more comprehensively. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/500202v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@4fbe48org.highwire.dtl.DTLVardef@15588edorg.highwire.dtl.DTLVardef@90b394org.highwire.dtl.DTLVardef@1fde3e5_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2021

Enterotoxigenic Escherichia coli display a distinct growth phase before entry into stationary phase with shifts in tryptophan- fucose- and putrescine metabolism and degradation of neurotransmitter precursors

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in children and adults in endemic areas. Gene regulation of ETEC during growth in vitro and in vivo needs to be further evaluated, and here we describe the full transcriptome and metabolome of ETEC during growth from mid-logarithmic growth to stationary phase in rich medium (LB medium). We identified specific genes and pathways subjected to rapid transient alterations in gene expression and metabolite production during the transition between logarithmic to stationary growth. The transient phase during late exponential growth is different from the subsequent induction of stationary phase-induced genes, including stress and survival responses as described earlier. The transient phase was characterized by the repression of genes and metabolites involved in organic substance transport. Genes involved in fucose and putrescine metabolism were upregulated, and genes involved in iron transport were repressed. Expression of toxins and colonization factors were not changed, suggesting retained virulence. Metabolomic analyses showed that the transient phase was characterized by a drop of intracellular amino acids, e.g., L-tyrosine, L-tryptophan, L-phenylalanine, L-leucine, and L-glutamic acid, followed by increased levels at induction of stationary phase. A pathway enrichment analysis of the entire transcriptome and metabolome showed activation of pathways involved in the degradation of neurotransmitters aminobutyrate (GABA) and precursors of 5-hydroxytryptamine (serotonin). This work provides a comprehensive framework for further studies on transcriptional and metabolic regulation in pathogenic E. coli. ImportanceWe show that E. coli, exemplified by the pathogenic subspecies enterotoxigenic E. coli (ETEC), undergoes a stepwise transcriptional and metabolic transition into the stationary phase. At a specific entry point, E. coli induces activation and repression of specific pathways. This leads to a rapid decrease of intracellular levels of L-tyrosine, L-tryptophan, L-phenylalanine, L-leucine, and L-glutamic acid due to metabolism into secondary compounds. The resulting metabolic activity leads to an intense but short peak of indole production, suggesting that this is the previously described "indole peak," rapid decrease of intermediate molecules of bacterial neurotransmitters, increased putrescine and fucose uptake, increased glutathione levels, and decreased iron uptake. This specific transient shift in gene expression and metabolomics is short-lived and disappears when bacteria enter the stationary phase. We suggest it mainly prepares bacteria for ceased growth, but the pathways involved suggest that this transient phase substantially influences survival and virulence.

microbiology↗

bioRxiv2020

Mechanism of DNA surface exploration and operator bypassing during target search

Many proteins that bind specific DNA sequences search the genome by combining three dimensional (3D) diffusion in the cytoplasm with one dimensional (1D) sliding on non-specific DNA1-5. Here we combine resonance energy transfer and fluorescence correlation measurements to characterize how individual lac repressor (LacI) molecules explore DNA during the 1D phase of target search. To track the rotation of sliding LacI molecules on the microsecond time scale during DNA surface search, we use real-time single-molecule confocal laser tracking combined with fluorescence correlation spectroscopy (SMCT-FCS). The fluorescence signal fluctuations are accurately described by rotation-coupled sliding, where LacI traverses ~40 base pairs (bp) per revolution. This distance substantially exceeds the 10.5-bp helical pitch of DNA, suggesting that the sliding protein frequently hops out of the DNA groove, which would result in frequent bypassing of target sequences. Indeed, we directly observe such bypassing by single-molecule fluorescence resonance energy transfer (smFRET). A combined analysis of the smFRET and SMCT-FCS data shows that LacI at most hops one to two grooves (10-20 bp) every 250 s. Overall, our data suggest a speed-accuracy trade-off during sliding; the weak nature of non-specific protein-DNA interactions underlies operator bypassing but also facilitates rapid sliding. We anticipate that our SMCT-FCS method to monitor rotational diffusion on the microsecond time scale while tracking individual molecules with millisecond time resolution will be applicable to the real-time investigation of many other biological interactions and effectively extends the accessible time regime by two orders of magnitude.

biophysics↗