Sunyer, J. O. | Search bioRxiv

bioRxiv2024

PathoFact 2.0: An Integrative Pipeline for Predicting Antimicrobial Resistance Genes, Virulence Factors, Toxins and Biosynthetic Gene Clusters in Metagenomes

SummaryAntimicrobial resistance genes (ARGs) and virulence factors (VFs) are central contributors to the global health crisis surrounding drug-resistant infections. PathoFact, a bioinformatics pipeline introduced in 2021, provides insights into ARGs, VFs, and bacterial toxins from metagenomic data. However, recent advancements in bioinformatics highlight the need for an updated version of PathoFact. We introduce PathoFact 2.0, an enhanced pipeline for improved ARG, VF, and toxin prediction. Key updates include an updated machine learning (ML) model for VF identification, a new ML model for toxin identification, expanded hidden Markov model profiles, and the antiSMASH 7.0 integration for predicting biosynthetic gene clusters. These upgrades make PathoFact 2.0 a more powerful, user-friendly platform for predicting microbiome-based pathogenicity and resistance, offering a crucial tool for better understanding and addressing the challenges posed by antimicrobial resistance and infectious diseases. Availability and ImplementationPathoFact 2.0 is available for download at https://gitlab.lcsb.uni.lu/ESB/PathoFact2/.

bioinformatics↗

bioRxiv2023

Secretory IgM (sIgM) is an ancient master regulator of microbiota homeostasis and metabolism

The co-evolution between secretory immunoglobulins (sIgs) and microbiota began with the emergence of IgM over half a billion years ago. Yet, IgM function in vertebrates is mostly associated with systemic immunity against pathogens. sIgA and sIgT are the only sIgs known to be required in the control of microbiota homeostasis in warm- and cold-blooded vertebrates respectively. Recent studies have shown that sIgM coats a large proportion of the gut microbiota of humans and teleost fish, thus suggesting an ancient and conserved relationship between sIgM and microbiota early in vertebrate evolution. To test this hypothesis, we temporarily and selectively depleted IgM from rainbow trout, an old bony fish species. IgM depletion resulted in a drastic reduction in microbiota IgM coating levels and losses in gutassociated bacteria. These were accompanied by bacterial translocation, severe gut tissue damage, inflammation and dysbiosis predictive of metabolic shifts. Furthermore, depletion of IgM resulted in body weight loss and lethality in an experimental colitis model. Recovery of sIgM to physiological levels restores tissue barrier integrity, while microbiome homeostasis and their predictive metabolic capabilities are not fully restituted. Our findings uncover a previously unrecognized role of sIgM as an ancient master regulator of microbiota homeostasis and metabolism and challenge the current paradigm that sIgA and sIgT are the key vertebrate sIgs regulating microbiome homeostasis. One-Sentence SummaryIgM, the most ancient and conserved immunoglobulin in jawed vertebrates, is required for successful symbiosis with the gut microbiota.

immunology↗