VIRGO2: Unveiling the Functional and Ecological Complexity of the Vaginal Microbiome with an Enhanced Non-Redundant Gene Catalog DOI Creative Commons
Michael France, Issac Chaudry,

Lindsay Rutt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Despite the importance of cervicovaginal microbiome, mechanisms that govern its composition and drive impact on host physiology remain poorly understood. This study expands our understanding function ecology vaginal microbiome using VIRGO2, an enhanced non-redundant gene catalog comprising over 1.7 million well-annotated genes from body-site specific microbes viruses. Analyses VIRGO2 revealed novel insights, including identification previously uncharacterized bacteria, features mycobiome phageome, differential expression bacterial carbohydrate catabolic genes. Constructed 2,500 metagenomes 4,000 genomes, broadens geographic representation microbial diversity compared to predecessor. updated enables more precise profiling taxonomic functional metagenomic metatranscriptomic datasets. is a critical resource for integrative analyses communities their interactions with tissues, thereby enhancing mechanistic health disease.

Language: Английский

Dnaapler: A tool to reorient circular microbial genomes DOI Creative Commons
George Bouras, Susanna R. Grigson, Bhavya Papudeshi

et al.

The Journal of Open Source Software, Journal Year: 2024, Volume and Issue: 9(93), P. 5968 - 5968

Published: Jan. 11, 2024

Microorganisms found in natural environments are fundamental components of ecosystems and play vital roles various ecological processes.Studying their genomes can provide valuable insights into the diversity, functionality, evolution microbial life, as well impacts on human health.Once genetic material is extracted from environmental samples, it undergoes sequencing using technologies like whole genome (WGS).The raw sequence data then analysed, computational methods applied to assemble fragmented sequences reconstruct complete (Wick et al.,

Language: Английский

Citations

36
Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication DOI Creative Commons
Enea Maffei,

Anne-Kathrin Woischnig,

Marco Burkolter

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly a slow- or non-growing, dormant state. Here, we show diverse phages can infect deep-dormant bacteria and suspend replication until the host resuscitates (“hibernation”). newly isolated Pseudomonas aeruginosa phage, named Paride, directly replicate induce lysis While non-growing notoriously tolerant to antibiotic drugs, combination with Paride enables carbapenem meropenem eradicate vitro reduce resilient infection tissue cage implant mice. Our work might inspire new treatments for persistent infections and, more broadly, highlights two strategies (hibernation direct replication) will guide future studies on phage-host interactions.

Language: Английский

Citations

32
Phage therapy DOI
Mikael Skurnik,

Sivan Alkalay‐Oren,

Maarten Boon

et al.

Nature Reviews Methods Primers, Journal Year: 2025, Volume and Issue: 5(1)

Published: Feb. 13, 2025

Citations

4
Gauge your phage: benchmarking of bacteriophage identification tools in metagenomic sequencing data DOI Creative Commons
Siu Fung Stanley Ho, Nicole E. Wheeler, Andrew Millard

et al.

Microbiome, Journal Year: 2023, Volume and Issue: 11(1)

Published: April 21, 2023

Abstract Background The prediction of bacteriophage sequences in metagenomic datasets has become a topic considerable interest, leading to the development many novel bioinformatic tools. A comparative analysis ten state-of-the-art phage identification tools was performed inform their usage microbiome research. Methods Artificial contigs generated from complete RefSeq genomes representing phages, plasmids, and chromosomes, previously sequenced mock community containing four species, were used evaluate precision, recall, F1 scores We also dataset randomly shuffled quantify false-positive calls. In addition, set simulated viromes assess diversity bias each tool’s output. Results VIBRANT VirSorter2 achieved highest (0.93) artificial dataset, with several other performing well. Kraken2 had score (0.86) benchmark by large margin (0.3 higher than DeepVirFinder second place), mainly due its high precision (0.96). Generally, k-mer-based better reference similarity gene-based methods. Several tools, most notably PPR-Meta, called number false positives sequences. When analysing that tool predicted virome set, produced viral genome similar alpha- beta-diversity patterns original population, Seeker being notable exception. Conclusions This study provides key metrics performance detection offers framework for further comparison additional discovery discusses optimal strategies using these highlight choice phages datasets, as well parameters, can results provide pointers different use case scenarios. have made our benchmarking available download order facilitate future comparisons

Language: Английский

Citations

34
Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients DOI Creative Commons
Mireia Bernabéu-Gimeno,

Marco Pardo-Freire,

Benjamin K. Chan

et al.

Med, Journal Year: 2024, Volume and Issue: 5(9), P. 1096 - 1111.e6

Published: June 24, 2024

Language: Английский

Citations

15
Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages DOI Creative Commons
Arturo Carabias, Sarah Camara-Wilpert, Mario Rodríguez Mestre

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(11), P. 2185 - 2202.e12

Published: May 23, 2024

Language: Английский

Citations

13
A long-context language model for deciphering and generating bacteriophage genomes DOI Creative Commons
Bin Shao, Jiawei Yan

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 30, 2024

Inspired by the success of large language models (LLMs), we develop a long-context generative model for genomes. Our multiscale transformer model, megaDNA, is pre-trained on unannotated bacteriophage genomes with nucleotide-level tokenization. We demonstrate foundational capabilities our including prediction essential genes, genetic variant effects, regulatory element activity and taxonomy sequences. Furthermore, it generates de novo sequences up to 96 K base pairs, which contain potential elements annotated proteins phage-related functions.

Language: Английский

Citations

11
A Klebsiella-phage cocktail to broaden the host range and delay bacteriophage resistance both in vitro and in vivo DOI Creative Commons

Huanchang Chen,

Haifeng Liu, Yanchun Gong

et al.

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Nov. 14, 2024

Bacteriophages (phages), viruses capable of infecting and lysing bacteria, are a promising alternative for treating infections from hypervirulent, antibiotic-resistant pathogens like Klebsiella pneumoniae, though narrow host range phage resistance remain challenges. In this study, the hypervirulent K. pneumoniae NTUH-K2044 was used to purify ΦK2044, while two ΦK2044-resistant strains were further phages: ΦKR1, ΦKR8 hospital sewage. A detailed characterization showed that ΦK2044 specifically killed KL1 capsule-type ΦKR1 targeted 13 different capsular serotypes. The cocktail (ΦK2044 + ΦKR8) effectively in biofilms, pre-treatment biofilm formation, delayed phage-resistance. improved 7-day survival Galleria mellonella mouse models therapeutic potential catheter model. summary, proof-of-principle has broad range, including highly drug-resistant serves as starting point optimizing therapy.

Language: Английский

Citations

10
Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant Serratia marcescens -induced pulmonary infection DOI Creative Commons
Xiangke Duan, Wenfeng Liu,

Yanyu Xiao

et al.

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 7, 2025

Serratia marcescens (S. marcescens) commonly induces refractory infection due to its multidrug-resistant nature. To date, there have been no reports on the application of phage treatment for S. infection. This study was conducted explore feasibility in treating by collaborating with a 59-year-old male patient pulmonary marcescens. Our experiments included three domains: i) selection appropriate phage, ii) verification efficacy and safety selected iii) confirmation phage-bacteria interactions. results showed that Spe5P4 is Treatment good efficacy, manifested as amelioration symptoms, hydrothorax examinations, chest computed tomography findings. Phage did not worsen hepatic renal function, immunity-related indices, or indices routine blood examination. It induce deteriorate drug resistance involved antibiotics. Importantly, adverse events were reported during follow-up periods. Thus, satisfactory safety. Finally, we found increase bacterial load, cytotoxicity, virulence, marcescens, indicating interactions between which are useful future against work provides evidence working basis further infections. We also provided methodological investigating clinical infections future.

Language: Английский

Citations

2
“Sichuanvirus”, a novel bacteriophage viral genus, able to lyse carbapenem-resistant Klebsiella pneumoniae DOI Creative Commons
Juan Li, Qingqing Fang,

Huan Luo

et al.

BMC Microbiology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 13, 2025

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a severe threat for human health and urgently needs new therapeutic approaches. Lytic bacteriophages (phages) are promising clinically viable options against CRKP. We attempted to isolate lytic phages CRKP of sequence type 11 capsular 64 (ST11-KL64), the predominant in China. recovered phage from sewage collected at wastewater treatment station Sichuan province, obtained genome this found that it distinct all known with highest overall DNA similarity (12.5%, 16% coverage 78.4% identity) vB_EcoM_PHB05 (accession no. NC_052652) ICTV. This represents novel viral genus subfamily Stephanstirmvirinae, which we proposed "Sichuanvirus" as name. has narrow host range lyse specific KL64 Klebsiella. no genes referring antimicrobial resistance, virulence, lysogen stable wide pH temperatures. also three bacterial mutants resistant performed sequencing them. therefore discovered interruption polysaccharide biosynthesis-related gene wcaJ by insertion sequences mediated resistance phage. characterized "Sichuanvirus", suitable therapy. The discovery expands arsenal

Language: Английский

Citations

2