Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae.

BACKGROUND: Klebsiella pneumoniae is a recognised agent of multidrug-resistant (MDR) healthcare-associated infections; however, individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin (iuc) and salmochelin (iro) are associated with invasive disease and are common amongst hypervirulent K. pneumoniae clones that cause severe community-associated infections such as liver abscess and pneumonia. Concerningly, iuc has also been reported in MDR strains in the hospital setting, where it was associated with increased mortality, highlighting the need to understand, detect and track the mobility of these virulence loci in the K. pneumoniae population. METHODS: Here, we examined the genetic diversity, distribution and mobilisation of iuc and iro loci amongst 2503 K. pneumoniae genomes using comparative genomics approaches and developed tools for tracking them via genomic surveillance. RESULTS: Iro and iuc were detected at low prevalence (< 10%). Considerable genetic diversity was observed, resolving into five iro and six iuc lineages that show distinct patterns of mobilisation and dissemination in the K. pneumoniae population. The major burden of iuc and iro amongst the genomes analysed was due to two linked lineages (iuc1/iro1 74% and iuc2/iro2 14%), each carried by a distinct non-self-transmissible IncFIBK virulence plasmid type that we designate KpVP-1 and KpVP-2. These dominant types also carry hypermucoidy (rmpA) determinants and include all previously described virulence plasmids of K. pneumoniae. The other iuc and iro lineages were associated with diverse plasmids, including some carrying IncFII conjugative transfer regions and some imported from Escherichia coli; the exceptions were iro3 (mobilised by ICEKp1) and iuc4 (fixed in the chromosome of K. pneumoniae subspecies rhinoscleromatis). Iro/iuc mobile genetic elements (MGEs) appear to be stably maintained at high frequency within known hypervirulent strains (ST23, ST86, etc.) but were also detected at low prevalence in others such as MDR strain ST258. CONCLUSIONS: Iuc and iro are mobilised in K. pneumoniae via a limited number of MGEs. This study provides a framework for identifying and tracking these important virulence loci, which will be important for genomic surveillance efforts including monitoring for the emergence of hypervirulent MDR K. pneumoniae strains

Cultivating Agricultural Literacy: Challenge for the Liberal Arts

A review and analysis of 11 pacesetting experiments funded by the W. K. Kellogg Foundation to generate greater awareness among liberal arts students and faculty about the role and importance ofthe agriculture enterprise to the nation

A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex.

Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella, highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes

Interacting meaningfully with machine learning systems: Three experiments

Although machine learning is becoming commonly used in today's software, there has been little research into how end users might interact with machine learning systems, beyond communicating simple “right/wrong” judgments. If the users themselves could work hand-in-hand with machine learning systems, the users’ understanding and trust of the system could improve and the accuracy of learning systems could be improved as well. We conducted three experiments to understand the potential for rich interactions between users and machine learning systems. The first experiment was a think-aloud study that investigated users’ willingness to interact with machine learning reasoning, and what kinds of feedback users might give to machine learning systems. We then investigated the viability of introducing such feedback into machine learning systems, specifically, how to incorporate some of these types of user feedback into machine learning systems, and what their impact was on the accuracy of the system. Taken together, the results of our experiments show that supporting rich interactions between users and machine learning systems is feasible for both user and machine. This shows the potential of rich human–computer collaboration via on-the-spot interactions as a promising direction for machine learning systems and users to collaboratively share intelligence

Deep Underground Science and Engineering Laboratory - Preliminary Design Report

The DUSEL Project has produced the Preliminary Design of the Deep Underground Science and Engineering Laboratory (DUSEL) at the rehabilitated former Homestake mine in South Dakota. The Facility design calls for, on the surface, two new buildings - one a visitor and education center, the other an experiment assembly hall - and multiple repurposed existing buildings. To support underground research activities, the design includes two laboratory modules and additional spaces at a level 4,850 feet underground for physics, biology, engineering, and Earth science experiments. On the same level, the design includes a Department of Energy-shepherded Large Cavity supporting the Long Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates one laboratory module and additional spaces for physics and Earth science efforts. With input from some 25 science and engineering collaborations, the Project has designed critical experimental space and infrastructure needs, including space for a suite of multidisciplinary experiments in a laboratory whose projected life span is at least 30 years. From these experiments, a critical suite of experiments is outlined, whose construction will be funded along with the facility. The Facility design permits expansion and evolution, as may be driven by future science requirements, and enables participation by other agencies. The design leverages South Dakota's substantial investment in facility infrastructure, risk retirement, and operation of its Sanford Laboratory at Homestake. The Project is planning education and outreach programs, and has initiated efforts to establish regional partnerships with underserved populations - regional American Indian and rural populations

Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations.

Mobile genetic elements (MGEs) that frequently transfer within and between bacterial species play a critical role in bacterial evolution, and often carry key accessory genes that associate with a bacteria's ability to cause disease. MGEs carrying antimicrobial resistance (AMR) and/or virulence determinants are common in the opportunistic pathogen Klebsiella pneumoniae, which is a leading cause of highly drug-resistant infections in hospitals. Well-characterised virulence determinants in K. pneumoniae include the polyketide synthesis loci ybt and clb (also known as pks), encoding the iron-scavenging siderophore yersiniabactin and genotoxin colibactin, respectively. These loci are located within an MGE called ICEKp, which is the most common virulence-associated MGE of K. pneumoniae, providing a mechanism for these virulence factors to spread within the population. Here we apply population genomics to investigate the prevalence, evolution and mobility of ybt and clb in K. pneumoniae populations through comparative analysis of 2498 whole-genome sequences. The ybt locus was detected in 40 % of K. pneumoniae genomes, particularly amongst those associated with invasive infections. We identified 17 distinct ybt lineages and 3 clb lineages, each associated with one of 14 different structural variants of ICEKp. Comparison with the wider population of the family Enterobacteriaceae revealed occasional ICEKp acquisition by other members. The clb locus was present in 14 % of all K. pneumoniae and 38.4 % of ybt+ genomes. Hundreds of independent ICEKp integration events were detected affecting hundreds of phylogenetically distinct K. pneumoniae lineages, including at least 19 in the globally-disseminated carbapenem-resistant clone CG258. A novel plasmid-encoded form of ybt was also identified, representing a new mechanism for ybt dispersal in K. pneumoniae populations. These data indicate that MGEs carrying ybt and clb circulate freely in the K. pneumoniae population, including among multidrug-resistant strains, and should be considered a target for genomic surveillance along with AMR determinants

Small IncQ1 and Col-Like Plasmids Harboring bla KPC-2 and Non-Tn4401 Elements (NTEKPC-IId) in High-Risk Lineages of Klebsiella pneumoniae CG258.

A retrospective genomic study led to the identification of two carbapenem-resistant K. pneumoniae isolates (KPN535 and KPC45) carrying bla KPC-2 genes on non-conjugative plasmids.…

Getting to the information you already have

Knowledge workers need to find information but even when it is stored on their local computer systems, finding it can be costly. There are many researchers working on solutions to reduce these costs, but there has been little research into exactly what these costs are, and what the ties are be-tween these costs and users' choices between ways to access their local information. This paper provides a methodology for investigating such issues, and reports empirical results on ways of accessing local, task-relevant resources (e.g. document files), their associated costs, and users' sensitivities to certain kinds of costs. Our results fill in gaps in what has been known about the problem, thereby helping to inform research on solutions to the problem.Keywords: user costs, accessing resources, Information storage and retrieval, finding information, opening files, Information interfaces and presentation, User interface

Corrigendum: 'Nanopore-only assemblies for genomic surveillance of the global priority drug-resistant pathogen, Klebsiella pneumoniae'.

In the published version of the article, there were errors in the read accessions provided in Table S1, which are now fixed. The updated file (TableS1_v2_13March2023.csv) can be accessed on Figshare using the DOI: 10.6084/m9.figshare.19745608. Furthermore, we would like to correct the following sentence in the Data Summary section of the published version: ‘Illumina reads have been deposited in the NCBI SRA, under the BioProject ID: PRJEB6891, and ONT reads (SUP basecalled) have been deposited under BioProject PRJNA646837.’ The sentence should read: ‘Illumina and ONT reads have been deposited in the NCBI SRA, under the BioProject IDs: PRJEB6891, PRJNA646837 and PRJNA351909.’