Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks.

Antibiotic resistance in the environment.

Bacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available human stool metagenomes. Over 75% of genomes represent double-stranded DNA phages that infect members of the Bacteroidia and Clostridia classes. Based on sequence clustering we identified 54,118 candidate viral species, 92% of which were not found in existing databases. The Metagenomic Gut Virus catalogue improves detection of viruses in stool metagenomes and accounts for nearly 40% of CRISPR spacers found in human gut Bacteria and Archaea. We also produced a catalogue of 459,375 viral protein clusters to explore the functional potential of the gut virome. This revealed tens of thousands of diversity-generating retroelements, which use error-prone reverse transcription to mutate target genes and may be involved in the molecular arms race between phages and their bacterial hosts.

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Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome.

The environment, including animals and animal products, is colonized by bacterial species that are typical and specific of every different ecological niche. Natural and human-related ecological pressure promotes the selection and expression of genes related to antimicrobial resistance (AMR). These genes might be present in a bacterial consortium but might not necessarily be expressed. Their expression could be induced by the presence of antimicrobial compounds that could originate from a given ecological niche or from human activity. In this work, we applied (meta)proteomics analysis of bacterial compartment of raw milk in order to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition. Results from milk analysis revealed the presence of 29 proteins/proteoforms linked to AMR. The detection of mainly β-lactamases suggests the possibility of using the milk microbiome as a bioindicator for the investigation of AMR. Moreover, it was possible to achieve a culture-free qualitative and functional analysis of raw milk bacterial consortia.

https://www.mdpi.com/2076-2615/10/12/2378/pdf

Raw Cow Milk Bacterial Consortium as Bioindicator of Circulating Anti-Microbial Resistance (AMR).

The platform consists of three modules, which are pre-configured bioinformatic pipelines, cloud toolsets, and online omics' courses. The pre-configured bioinformatic pipelines not only combine analytic tools for metagenomics, genomes, transcriptome, proteomics and metabolomics, but also provide users with powerful and convenient interactive analysis reports, which allow them to analyze and mine data independently. As a useful supplement to the bioinformatics pipelines, a wide range of cloud toolsets can further meet the needs of users for daily biological data processing, statistics, and visualization. The rich online courses of multi-omics also provide a state-of-art platform to researchers in interactive communication and knowledge sharing. 

Majorbio Cloud: A one‐stop, comprehensive bioinformatic platform for multiomics analyses

Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects.

The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.

/pdf/card-2020-antibiotic-resistome-surveillance-with-the-3xmj98zunn.pdf

CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database

To evaluate the epidemiology, presentation and management of hypoparathyroidism in Canada. Hypoparathyroidism is associated with significant morbidity and poor quality of life. We present baseline results from the Canadian National Hypoparathyroidism Registry, a prospective observational study evaluating hypoparathyroidism in Canada. Our study enrolled 130 patients with hypoparathyroidism. Patients were followed every 6 months with clinical and lab assessments. We present baseline data in this manuscript. Seventy percent (91/130) of patients had postsurgical hypoparathyroidism, 30% (39/130) of patients had nonsurgical hypoparathyroidism due to autoimmune, genetic or idiopathic causes, and a molecular diagnosis was confirmed in 11 of these 39 patients. Pseudohypoparathyroidism was confirmed in 4/39 patients, DiGeorge syndrome in 2/39 patients, Barakat syndrome with a mutation in the GATA3 gene in 1/39, and activating mutations of the CASR gene in 3/39 patients with nonsurgical hypoparathyroidism. Renal complications with nephrocalcinosis or nephrolithiasis were present in 27% (14/52) of patients with postsurgical disease and 17% (4/24) of patients with nonsurgical hypoparathyroidism. Basal ganglia calcification was noted on imaging in 15% (n = 5/34) of patients with postsurgical hypoparathyroidism and 37% (n = 7/19) of patients with nonsurgical hypoparathyroidism. Hypercalciuria was more commonly seen in those with renal complications of nephrocalcinosis, nephrolithiasis or CKD, and hyperphosphatemia was more commonly seen in those with basal ganglia calcification. Hospitalization occurred in 28% of those with postsurgical hypoparathyroidism and 46% of those with nonsurgical hypoparathyroidism. Hypoparathyroidism is associated with significant morbidity. Effective strategies to reduce the short-and long-term complications of hypoparathyroidism need to be developed and evaluated.

Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada.

Abstract The Canadian National Hypoparathyroidism Registry (CNHR) was formed in 2014 and enrolment of prevalent and incident cases began following approval by McMaster University Ethics Review Board. Objective(s): • identify the etiology and presenting symptoms of patients with hypoPTH. • assess differences in presentation based on etiology of the disease. • compare parameters of calcium homeostasis amongst those developing complications of nephrolithiasis or nephrocalcinosis and those without complications. • assess fracture risk in Canadian patients with hypoPTH. Material and Methods: 118 patients aged >18 years registered in the CNHR were reviewed as per the following inclusion criteria: 1. Chronic HypoPTH (low PTH in the presence of low serum calcium total or ionized below normal reference range for at least 6 months prior to enrolment) 2. HypoPTH (including post-surgery) requiring calcium/calcitriol replacement to maintain normal calcium (total or ionized calcium level for at least 6 months prior to enrolment 3. Pseudohypoparathyroidism with elevated PTH and low serum calcium (total or ionized) normal vitamin D and hyperphosphatemia were included. We reviewed etiology, clinical presentation, biochemical profile, management strategies, markers of skeletal health including fractures, bone mineral density (BMD), fracture risk and complications including nephrolithiasis/nephrocalcinosis, and basal ganglia calcification. Results: Most patients (72%) had postsurgical hypoparathyroidism, followed by idiopathic/autoimmune disease (25%) and pseudohypoparathyroidism (3%). The mean age of onset was 42.0 years, with mean duration of follow-up of 4 years. All patients were taking calcium supplements (100%); calcitriol was taken by 82.2% and 6 patients were receiving parathyroid hormone. Nephrolithiasis or nephrocalcinosis were present in 24.6% of treated patients despite a mean calcium phosphate product <4.4 mmol2/L2. Basal ganglia calcification was present in 8 of the 30 patients reviewed. Hospitalization was required in 40 of the 118 patients for symptoms of hypocalcemia. Conclusion: 1. HypoPTH is associated with a significant disease burden and leads to hospitalization in a large number of patients. 2. Renal complications were present in 24.6% of treated patients despite maintenance of a calcium phosphate product in the desired range (<4.4 mmol2/L2). The ideal calcium phosphate product needs to be reconsidered. 3. Fracture risk was low in the absence of traditional osteoporosis risk factors. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

MON-LB091 An Overview of the Etiology, Clinical Manifestations, Management Strategies, and Complications of Hypoparathyroidism from the Canadian National Hypoparathyroidism Registry

Rafik El Werfalli

Papers

CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database

Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada.

MON-LB091 An Overview of the Etiology, Clinical Manifestations, Management Strategies, and Complications of Hypoparathyroidism from the Canadian National Hypoparathyroidism Registry