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Eisenhard, L.

Publications and source records attributed to Eisenhard, L..

3 recordsLinked to original sources

Metabolites produced by gut bacteria under anoxic conditions drive the suppression of Acinetobacter baumannii

Multidrug-resistant (MDR) bacteria pose a significant global health threat. Among these, Acinetobacter baumannii, particularly carbapenem-resistant A. baumannii, is a leading cause of healthcare-associated infections. Emerging evidence links gut colonization to systemic infections, highlighting opportunities for new control strategies. We demonstrate that A. baumannii can survive under anaerobic conditions ([≤]1%) and shows limited growth under low oxygen conditions ([≥]1%), underscoring its adaptation to niches in the intestine. However, specific carbohydrates, including maltose, provide the gut bacteria Klebsiella oxytoca with a competitive advantage under anoxic conditions, enabling it to actively suppress A. baumannii through its metabolism. Notably, maltose induces this suppressive capacity in other commensals and complex gut microbiomes as well. Force-feeding experiments in Galleria mellonella larvae corroborate that K. oxytoca in combination with maltose significantly reduces A. baumannii recovery in gut environments. These findings suggest that targeted carbohydrate supplementation could enhance probiotic strategies, creating an environment unfavorable to A. baumannii.

microbiology↗

Gene-centric metagenomic analyses reveal microbiome functional insights into diseases

The microbiome encodes millions of genes; however, understanding their role in human health remains challenging. Here, we developed MetaGEAR, a gene-centric analysis framework for metagenomic data. MetaGEAR constructs cohort-specific databases for efficient retrieval of gene annotations, abundances, and co-localization, while providing enhanced taxonomic resolution by integrating reference- and assembly-based approaches. This is combined with a Metagenomic Assembled Graph (MAGraph) capturing gene neighborhood information. Using MetaGEAR, we built a multi-cohort database comprising >33 million gene families to investigate microbiome functionality across 24 cohorts of inflammatory bowel disease, colorectal cancer, and healthy populations and identified disease signature genes. Furthermore, the MAGraph revealed mobile genetic elements acting as hubs for tetracycline resistance spreading among Enterococcus, Streptococcus, and Veillonella species. Also, a duplicated nitrate reduction operon in Klebsiella pneumoniae was linked to differential gene expression under stress and virulence-inducing conditions. In summary, gene-centric metagenomic analyses reveal important insights into microbiome functionality in diseases.

microbiology↗

Rapid Directed Molecular Evolution of Fluorescent Proteins in Mammalian Cells

In vivo imaging of model organisms is heavily reliant on fluorescent proteins with high intracellular brightness. Here we describe a practical method for rapid optimization of fluorescent proteins via directed molecular evolution in cultured mammalian cells. Using this method, we were able to perform screening of large gene libraries containing up to 2{middle dot}107 independent random genes of fluorescent proteins expressed in HEK cells completing one iteration directed evolution in a course of [~]8 days. We employed this approach to develop a set of green and near-infrared fluorescent proteins with enhanced intracellular brightness. The developed near-infrared fluorescent proteins demonstrated high performance for fluorescent labeling of neurons in culture and in vivo in model organisms such as C.elegans, Drosophila, zebrafish, and mice. Spectral properties of the optimized near-infrared fluorescent proteins enabled crosstalk-free multicolor imaging in combination with common green and red fluorescent proteins, as well as dual-color near-infrared fluorescence imaging. The described method has a great potential to be adopted by protein engineers due to its simplicity and practicality. We also believe that the new enhanced fluorescent proteins will find wide application for in vivo multicolor imaging of small model organisms.

molecular biology↗