Biology subjects

Loerzing, P.

Publications and source records attributed to Loerzing, P..

3 recordsLinked to original sources

bioRxiv2026

Nucleoid compaction during antibiotic stress excludes the SOS regulator LexA

The bacterial SOS response promotes DNA repair, survival, and mutagenesis under genotoxic stress, especially during sub-lethal antibiotic exposure. This response is regulated by LexA, a transcriptional repressor controlling SOS gene expression, but how LexA coordinates this network as antibiotic stress alters nucleoid structure is unclear. Using ciprofloxacin-induced DNA damage, we investigated how increasing antibiotic stress affects the spatial relationship between LexA and the nucleoid in single E. coli cells. Through 3D single-molecule imaging and functional assays, we found that sublethal ciprofloxacin doses activated SOS, expanded nucleoids, and maintained LexA association. In contrast, higher stress caused severe DNA damage, compacted nucleoids, and LexA exclusion, yet some cells remained viable and recovered after drug removal. These results demonstrate that the SOS response involves both temporal and spatial regulation, with LexA and nucleoid organization adapting to damage severity to modulate SOS functions.

microbiology↗

bioRxiv2026

Active destabilization of the integron synaptic complex reduces bacterial adaptation to antibiotics

Antibiotic multi-resistance (AMR) in bacteria poses a significant threat to global health, driven by mechanisms like the integron genetic system in Gram-negative bacteria. Integrons facilitate AMR by shuffling resistance genes through site-specific recombination, mediated by the integrase enzyme IntI. Earlier studies revealed that the mechanical stability of the synaptic complex, a structure formed by four integrase subunits and DNA, correlates with the recombination efficiency, and, by extension, the adaptation capability. We identified a conserved C-terminal -helix in IntI that stabilizes the synaptic complex via specific interactions with a binding pocket. To disrupt this interaction, we designed peptides mimicking the -helix, which reduced the mechanical stability probed with single-molecule optical tweezers. In bacterial adaptation assays, these peptides significantly decreased integron-mediated adaptation to ciprofloxacin stress without exhibiting antimicrobial activity. This approach highlights a novel strategy to combat AMR by targeting integron-mediated gene shuffling, offering potential for future therapeutic development to limit the spread of resistance genes.

biophysics↗

bioRxiv2025

Spatiotemporal Dynamics of the Dihydrolipoyl Dehydrogenase LpdA Determine the Intrinsic Autofluorescence in Filamentous Actinobacteria

The hyphal nature of filamentous streptomycetes poses unique challenges to their multicellular lifestyle, since it requires organizing cellular functions at the scale of hundreds of micrometers length. Streptomycetes exhibit a strong and patchy autofluorescence of so far unknown origin in their hyphae that - as we demonstrate - is a natural property of filamentous actinobacteria. The foci are dynamic and evenly distributed throughout the hyphae, including the hyphal tips, where they are cell membrane-associated. Here, we resolved the high spatiotemporal dynamics of these foci during spore germination and vegetative growth in Streptomyces venezuelae. We isolated a fluorescent protein band and identified the responsible protein as dihydrolipoyl dehydrogenase LpdA. An lpdA deletion mutant lacked these fluorescent foci and showed minor deficiencies in growth and development. Heterologous LpdA production in E. coli and characterization of the enzyme verified that a flavin cofactor is responsible for the green autofluorescence. LpdA is highly conserved in actinomycetes as a part of multienzyme complexes involved in central metabolism. Such delocalized metabolic centers provide a potential solution to mycelial multicellular lifestyle, where diffusion becomes a major challenge.

microbiology↗