Biology subjects

Sari, T.

Publications and source records attributed to Sari, T..

3 recordsLinked to original sources

bioRxiv2026

Prevalent Gut Phages Encode Modular Adhesins Mediating Epithelial Binding and Endoplasmic Reticulum Trafficking

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. The identified phages encode immunoglobulin (Ig)-like domain-containing proteins that, when displayed on a non-adherent phage, confer epithelial binding and internalization in vitro, and increased phage retention in the mouse gut in vivo. Phages encoding these adhesins are among the most abundant and prevalent human gut phages, including crAss-like phages and a distinct cluster of uncharacterized myophages. Domain sequence variation alters epithelial interaction profiles, and internalized phages traffic to the endoplasmic reticulum through the Golgi apparatus, suggesting access to non-degradative internalization pathways. These findings reveal widespread phage-human interactions in the human virome, with potential impacts on health and implications for next-generation phage therapeutics.

microbiology↗

bioRxiv2023

Antibiotics of the future are prone to resistance in Gram-negative pathogens

Despite the ongoing development of new antibiotics, the future evolution of bacterial resistance may render them ineffective. We demonstrate that antibiotic candidates currently under development are as prone to resistance evolution in Gram-negative pathogens as clinically employed antibiotics. Resistance generally stems from both genomic mutations and the transfer of antibiotic resistance genes from microbiomes associated with humans, both factors carrying equal significance. The molecular mechanisms of resistance overlap with those found in commonly used antibiotics. Therefore, these mechanisms are already present in natural populations of pathogens, indicating that resistance can rapidly emerge through selection of pre-existing bacterial variants. However, certain combinations of antibiotics and bacterial strains are less prone to developing resistance, emphasizing the potential of narrow-spectrum antibacterial therapies that could remain effective. Our comprehensive framework allows for predicting future health risks associated with bacterial resistance to new antibiotics.

microbiology↗

bioRxiv2018

Enhancing the translational capacity of E. coli by resolving the codon bias

Escherichia coli is a well-established, and popular host for heterologous expression of proteins. The preference in the choice of synonymous codons (codon bias), however, might differ for the host and the original source of the recombinant protein, constituting a potential bottleneck in production. Codon choice affects the efficiency of translation by a complex and poorly understood mechanism. The availability of certain tRNA species is one of the factors that may curtail the capacity of translation.\n\nHere we provide a tRNA-overexpressing strategy that allows the resolution of the codon bias, and boosts the translational capacity of the popular host BL21(DE3) when rare codons are encountered. In BL21(DE3)-derived strain, called SixPack, copies of the genes corresponding to the six least abundant tRNA species have been assembled in a synthetic fragment and inserted into a ribosomal RNA operon. This arrangement, while not interfering with the growth properties of the new strain, allows dynamic control of the transcription of the extra tRNA genes, providing significantly elevated levels of the rare tRNAs in exponential growth phase.\n\nResults from expression assays of a panel of heterologous proteins of diverse origin and codon composition showed that the performance of SixPack surpassed that of the parental BL21(DE3) or a related strain equipped with a rare tRNA-expressing plasmid.\n\nImportanceCodon composition not fitting the codon bias of the expression host frequently compromises the efficient production of foreign proteins in E. coli. Various attempts to remedy the problem (codon optimization by gene synthesis, expression of rare tRNAs from a plasmid) proved to be unsatisfying. Our new approach, adjusting the tRNA pool by co-expressing extra copies of rare tRNA genes with ribosomal RNA genes, does not affect normal cell physiology, and seems to be a superior solution in terms of simplicity, cost, and yield.

synthetic biology↗