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Articles by Csaba Pál
Predicting resistance evolution to guide antibiotic development
Abstract Antibiotic resistance has emerged as a major bottleneck in antibiotic development, frequently undermining promising drug candidates and negating years of research and pharmaceutical investment. Despite growing recognition of this issue, discovery pipelines still emphasize potency and target specificity whereas resistance potential is often considered later in the development process.
Deep-learning single-cell profiling uncovers interbacterial and drug-driven reshaping of pathogen virulence
Abstract Bacterial invasion and genotoxicity are key contributors to infectious disease progression and carcinogenesis. Yet current methods do not quantify these processes systematically and at single-cell resolution, limiting our ability to explore how interplay of virulence factors and drug effects shape pathogenicity.
HLA-II peptide-binding diversity shapes humoral immune responses and susceptibility to infections
Abstract Infectious diseases represent a leading cause of mortality worldwide and have shaped the evolution of the human immune system. Human leukocyte antigen (HLA) class II molecules are key to the humoral immune response by presenting peptides to helper T cells. The peptide-binding range varies greatly among HLA-II variants, but the role of this variation in humoral immunity and infection susceptibility has remained unexplored.
Prevalent gut phages encode modular adhesins mediating epithelial binding and endoplasmic reticulum trafficking
Abstract Bacteriophages are crucial components of the human microbiome and hold promise as therapeutic agents. Yet, their physical interactions with mammalian cells remain poorly understood. Here, we developed a high-throughput platform to identify phages that adhere to epithelial layers and the proteins that mediate this interaction.
Chemically diverse antimicrobial peptides induce hyperpolarization of the E. coli membrane - Communications Biology
Abstract The negative membrane potential within bacterial cells is crucial in various essential cellular processes. Sustaining a hyperpolarised membrane could offer a novel strategy to combat antimicrobial resistance. However, it remains uncertain which molecules are responsible for inducing hyperpolarization and what the underlying molecular mechanisms are.
Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains - Nature Microbiology
Abstract Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. Here we present a functional metagenomics pipeline called Reprogrammed Bacteriophage Particle Assisted Multi-species Functional Metagenomics (DEEPMINE).
Gene loss and compensatory evolution promotes the emergence of morphological novelties in budding yeast - Nature Ecology & Evolution
Abstract Deleterious mutations are generally considered to be irrelevant for morphological evolution. However, they could be compensated by conditionally beneficial mutations, thereby providing access to new adaptive paths. Here we use high-dimensional phenotyping of laboratory-evolved budding yeast lineages to demonstrate that new cellular morphologies emerge exceptionally rapidly as a by-product of gene loss and subsequent compensatory evolution.
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