Search bioRxiv⌕ Search

Biology subjects

Waffenschmidt, N.

Publications and source records attributed to Waffenschmidt, N..

2 recordsLinked to original sources

The PhageExpressionAtlas reveals shared and unique transcriptional patterns across phage-host interactions

Time-resolved transcriptomic profiling has been used to study phage-host interactions for more than a decade. However, the resulting datasets are not readily accessible for custom re-analysis, and resources are lacking that provide standardized processing, storage, and analysis of transcriptomes from phage infections. Here, we present the PhageExpressionAtlas, the first bioinformatics resource for storing time-resolved dual RNA-sequencing data from phage infections. This data was processed uniformly using a custom analysis pipeline and is presented for interactive exploration through visualisation. The PhageExpressionAtlas currently hosts 42 datasets from 23 studies. Using the PhageExpressionAtlas, we replicate key findings from original publications and extend hypothesis testing across multiple phage-host systems. By systematically querying and analyzing the underlying database, we evaluate approaches to phage gene classification and show that uncharacterized phage genes are expressed across all infection phases. Moreover, we provide a comprehensive view of the expression dynamics of anti-phage defenses as well as host- and phage-encoded anti-defense systems in the infection context, indicating unique and conserved patterns of transcriptional regulation underlying bacterial anti-phage immunity and phage counter-strategies. Together, the PhageExpressionAtlas is a unifying resource that democratizes transcriptomics-driven analyses of phage-host interactions and supports integrative cross-study assessment.

bioinformatics↗

Purine nucleotide limitation undermines antibiotic action in clinical Escherichia coli

Metabolic variation across pathogenic bacterial strains can impact their susceptibility to antibiotics1-4 and promote evolution of antimicrobial resistance (AMR)5,6. However, little is known about which metabolic pathways contribute to AMR, and the underlying mechanisms. Here, we measured antibiotic resistance of 15,120 Escherichia coli mutants, each with a single amino acid change in one of 346 essential proteins. Most of the mutant strains that showed resistance to either of the two tested antibiotics carried mutations in metabolic genes. Resistance mutations against a {beta}-lactam antibiotic (carbenicillin) were associated with purine nucleotide biosynthesis and limited the supply of ATP. We show that ATP limitation confers both resistance and tolerance against {beta}-lactam antibiotics by upregulating the purine nucleoside transporter PunC. These results are clinically relevant, because an E. coli strain isolated from a clinical specimen had a purine nucleotide limitation, which reduced its susceptibility to antibiotics.

microbiology↗