Polyomavirus large T antigens: Unraveling a complex interactome.

All members of the polyomavirus family encode a large T antigen (LT) protein that plays essential roles in viral DNA replication, regulation of viral gene expression, and the manipulation of numerous cellular pathways. Over 100 polyomaviruses have been discovered in hosts ranging from arthropods and fish to mammals, including fourteen that infect humans. LT is among the most studied viral proteins with thousands of articles describing its functions in viral productive infection and tumorigenesis.

Marked neurotropism and potential adaptation of H5N1 clade 2.3.4.4.b virus in naturally infected domestic cats.

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.

A Bioinformatic Ecosystem for Bacteriophage Genomics: PhaMMSeqs, Phamerator, pdm_utils, PhagesDB, DEPhT, and PhamClust.

The last thirty years have seen a meteoric rise in the number of sequenced bacteriophage genomes, spurred on by both the rise and success of groups working to isolate and characterize phages, and the rapid and significant technological improvements and reduced costs associated with sequencing their genomes. Over the course of these decades, the tools used to glean evolutionary insights from these sequences have grown more complex and sophisticated, and we describe here the suite of computational and bioinformatic tools used extensively by the integrated research-education communities such as SEA-PHAGES and PHIRE, which are jointly responsible for 25% of all complete phage genomes in the RefSeq database. These tools are used to integrate and analyze phage genome data from different sources, for identification and precise extraction of prophages from bacterial genomes, computing "phamilies" of related genes, and displaying the complex nucleotide and amino acid level mosaicism of these genomes.

PhamClust: a phage genome clustering tool using proteomic equivalence.

Bacteriophage genomes are pervasively mosaic, presenting challenges to describing phage relatedness. Here, we describe PhamClust, a bioinformatic approach for phage genome comparisons that uses a new metric of proteomic equivalence quotient for comparative genomics. PhamClust reliably assorts genomes into groups or clusters of related phages and can subdivide clusters into subclusters.

The heterogenous and diverse population of prophages in genomes.

species include several human pathogens and mycobacteriophages show potential for therapeutic use to control infections. However, phage infection profiles vary greatly among clinical isolates and phage therapies must be personalized for individual patients. phage susceptibility is likely determined primarily by accessory parts of bacterial genomes, and we have identified the prophage and phage-related genomic regions across sequenced strains.

PhaMMseqs: a new pipeline for constructing phage gene phamilies using MMseqs2.

The diversity and mosaic architecture of phage genomes present challenges for whole-genome phylogenies and comparative genomics. There are no universally conserved core genes, ∼70% of phage genes are of unknown function, and phage genomes are replete with small (<500 bp) open reading frames. Assembling sequence-related genes into "phamilies" ("phams") based on amino acid sequence similarity simplifies comparative phage genomics and facilitates representations of phage genome mosaicism.

DEPhT: a novel approach for efficient prophage discovery and precise extraction.

Advances in genome sequencing have produced hundreds of thousands of bacterial genome sequences, many of which have integrated prophages derived from temperate bacteriophages. These prophages play key roles by influencing bacterial metabolism, pathogenicity, antibiotic resistance, and defense against viral attack. However, they vary considerably even among related bacterial strains, and they are challenging to identify computationally and to extract precisely for comparative genomic analyses.

The Prophage and Plasmid Mobilome as a Likely Driver of Mycobacterium abscessus Diversity.

is an emerging pathogen that is often refractory to antibiotic control. Treatment is further complicated by considerable variation among clinical isolates in both their genetic constitution and their clinical manifestations. Here, we show that the prophage and plasmid mobilome is a likely contributor to this variation.

Mycobacterium abscessus Strain Morphotype Determines Phage Susceptibility, the Repertoire of Therapeutically Useful Phages, and Phage Resistance.

is an opportunistic pathogen whose treatment is confounded by widespread multidrug resistance. The therapeutic use of bacteriophages against infections offers a potential alternative approach, although the spectrum of phage susceptibilities among isolates is not known. We determined the phage infection profiles of 82 recent clinical isolates and find that colony morphotype-rough or smooth-is a key indicator of phage susceptibility.