Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes independent of their organization in functional gene clusters. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. We delineate gene clusters in the type strain A. baumannii ATCC 19606 whose evolutionary conservation indicates a functional integration of the subsumed genes. These evolutionarily stable gene clusters (ESGCs) reveal metabolic pathways, transcriptional regulators residing next to their targets but also tie together sub-clusters with distinct functions to form higher-order functional modules. We shortlisted 150 ESGCs that either co-emerged with the pathogenic ACB clade or are preferentially found therein. They provide a high-resolution picture of genetic and functional changes that coincide with the manifestation of the pathogenic phenotype in the ACB clade. Key innovations are the remodeling of the regulatory-effector cascade connecting LuxR/LuxI quorum sensing via an intermediate messenger to biofilm formation, the extension of micronutrient scavenging systems, and the increase of metabolic flexibility by exploiting carbon sources that are provided by the human host. We could show experimentally that only members of the ACB clade use kynurenine as a sole carbon and energy source, a substance produced by humans to fine-tune the antimicrobial innate immune response. In summary, this study provides a rich and unbiased set of novel testable hypotheses on how pathogenic Acinetobacter interact with and ultimately infect their human host. It is a comprehensive resource for future research into novel therapeutic strategies.Peer Reviewe

Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes independent of their organization in functional gene clusters. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. We delineate gene clusters in the type strain A. baumannii ATCC 19606 whose evolutionary conservation indicates a functional integration of the subsumed genes. These evolutionarily stable gene clusters (ESGCs) reveal metabolic pathways, transcriptional regulators residing next to their targets but also tie together sub-clusters with distinct functions to form higher-order functional modules. We shortlisted 150 ESGCs that either co-emerged with the pathogenic ACB clade or are preferentially found therein. They provide a high-resolution picture of genetic and functional changes that coincide with the manifestation of the pathogenic phenotype in the ACB clade. Key innovations are the remodeling of the regulatory-effector cascade connecting LuxR/LuxI quorum sensing via an intermediate messenger to biofilm formation, the extension of micronutrient scavenging systems, and the increase of metabolic flexibility by exploiting carbon sources that are provided by the human host. We could show experimentally that only members of the ACB clade use kynurenine as a sole carbon and energy source, a substance produced by humans to fine-tune the antimicrobial innate immune response. In summary, this study provides a rich and unbiased set of novel testable hypotheses on how pathogenic Acinetobacter interact with and ultimately infect their human host. It is a comprehensive resource for future research into novel therapeutic strategies

NFDI4Microbiota – national research data infrastructure for microbiota research

Microbes – bacteria, archaea, unicellular eukaryotes, and viruses – play an important role in human and environmental health. Growing awareness of this fact has led to a huge increase in microbiological research and applications in a variety of fields. Driven by technological advances that allow high-throughput molecular characterization of microbial species and communities, microbiological research now offers unparalleled opportunities to address current and emerging needs. As well as helping to address global health threats such as antimicrobial resistance and viral pandemics, it also has a key role to play in areas such as agriculture, waste management, water treatment, ecosystems remediation, and the diagnosis, treatment and prevention of various diseases. Reflecting this broad potential, billions of euros have been invested in microbiota research programs worldwide. Though run independently, many of these projects are closely related. However, Germany currently has no infrastructure to connect such projects or even compare their results. Thus, the potential synergy of data and expertise is being squandered. The goal of the NFDI4Microbiota consortium is to serve and connect this broad and heterogeneous research community by elevating the availability and quality of research results through dedicated training, and by facilitating the generation, management, interpretation, sharing, and reuse of microbial data. In doing so, we will also foster interdisciplinary interactions between researchers. NFDI4Microbiota will achieve this by creating a German microbial research network through training and community-building activities, and by creating a cloud-based system that will make the storage, integration and analysis of microbial data, especially omics data, consistent, reproducible, and accessible across all areas of life sciences. In addition to increasing the quality of microbial research in Germany, our training program will support widespread and proper usage of these services. Through this dual emphasis on education and services, NFDI4Microbiota will ensure that microbial research in Germany is synergistic and efficient, and thus excellent. By creating a central resource for German microbial research, NDFDI4Microbiota will establish a connecting hub for all NFDI consortia that work with microbiological data, including GHGA, NFDI4Biodiversity, NFDI4Agri and several others. NFDI4Microbiota will provide non-microbial specialists from these consortia with direct and easy access to the necessary expertise and infrastructure in microbial research in order to facilitate their daily work and enhance their research. The links forged through NFDI4Microbiota will not only increase the synergy between NFDI consortia, but also elevate the overall quality and relevance of microbial research in Germany

Aruna Object Storage: A distributed, domain-agnostic multi-cloud object storage for scientific data management

The exponential growth of scientific data has led to an increasing demand for effective data management and storage solutions. Academic computing infrastructures are often fragmented, which can make it challenging for researchers to leverage cloud-native principles and modern data analysis tools. To address this challenge, a new distributed storage platform called Aruna Object Storage (AOS) was developed. AOS is a cloud-native, scalable, and domain-agnostic object storage system that provides an S3-compatible interface for a variety of data analysis tools like Apache Spark, TensorFlow, and Pandas. The system uses an underlying distributed NewSQL database to manage detailed information about its resources and can be deployed across multiple data centers for geo-redundancy. AOS is designed to support modern DataOps practices, including the adoption of FAIR principles. Resources in AOS are organized into Objects, Datasets, Collections and Projects, which represent relations of data objects. Additionally, these can be further annotated with key-value pairs called Labels and Hooks to provide additional information about the data. The system's event-driven architecture makes it easy to automate actions and enforce data validation checks, significantly improving accessibility and reproducibility of scientific results. AOS is open source and freely available via https://aruna-storage.org

Towards a Research Data Commons in the German National Research Data Infrastructure NFDI: Vision, Governance, Architecture

The concept of a "Research Data Commons" (RDC) established itself as an infrastructure ecosystem for science based on open standards and federated resources to facilitate the sharing of research data and services. The consortia of the German National Research Data Infrastructure (NFDI) have identified the collaborative provisioning of resources and services to be of key importance for a functioning and efficient RDC and are leveraging different corresponding measures to establish a sustainable concept in line with international developments.</jats:p