The origins and potential future of SARS-CoV-2 variants of concern in the evolving COVID-19 pandemic.

One year into the global COVID-19 pandemic, the focus of attention has shifted to the emergence and spread of SARS-CoV-2 variants of concern (VOCs). After nearly a year of the pandemic with little evolutionary change affecting human health, several variants have now been shown to have substantial detrimental effects on transmission and severity of the virus. Public health officials, medical practitioners, scientists, and the broader community have since been scrambling to understand what these variants mean for diagnosis, treatment, and the control of the pandemic through nonpharmaceutical interventions and vaccines.

Aspergillomarasmine A inhibits metallo-β-lactamases by selectively sequestering Zn.

Class B metallo-β-lactamases (MBLs) are Zn-dependent enzymes that catalyze the hydrolysis of β-lactam antibiotics to confer resistance in bacteria. Several problematic groups of MBLs belong to subclass B1, including the binuclear New Delhi MBL (NDM), Verona integrin-encoded MBL, and imipenemase-type enzymes, which are responsible for widespread antibiotic resistance. Aspergillomarasmine A (AMA) is a natural aminopolycarboxylic acid that functions as an effective inhibitor of class B1 MBLs.

Aldehyde to Ketone Homologation Enabled by Improved Access to Thioalkyl Phosphonium Salts.

Phosphines were previously unusable as Pummerer-type nucleophiles due to competing redox chemistry with sulfoxides. Here we circumvent this problem to achieve a formal phosphine Pummerer reaction that offers thioalkyl phosphonium salts that, in turn, give rise to diverse vinyl sulfides via Wittig olefinations. Thirty vinyl sulfides are thus prepared from (alkylthioalkyl)triphenyl phosphonium salts and aldehydes.

Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts.

Temporal Dynamics and Evolution of SARS-CoV-2 Demonstrate the Necessity of Ongoing Viral Genome Sequencing in Ontario, Canada.

Genome-wide variation in SARS-CoV-2 reveals evolution and transmission dynamics which are critical considerations for disease control and prevention decisions. Here, we review estimates of the genome-wide viral mutation rates, summarize current COVID-19 case load in the province of Ontario, Canada (5 January 2021), and analyze published SARS-CoV-2 genomes from Ontario (collected prior to 24 November 2020) to test for more infectious genetic variants or lineages. The reported mutation rate (∼10 nucleotide [nt] cycle) for SARS-CoV-2 is typical for coronaviruses.

The Enzymes of the Rifamycin Antibiotic Resistome.

Rifamycin antibiotics include the WHO essential medicines rifampin, rifabutin, and rifapentine. These are semisynthetic derivatives of the natural product rifamycins, originally isolated from the soil bacterium . These antibiotics are primarily used to treat mycobacterial infections, including tuberculosis.

How to kill Pseudomonas-emerging therapies for a challenging pathogen.

As the number of effective antibiotics dwindled, antibiotic resistance (AR) became a pressing concern. Some Pseudomonas aeruginosa isolates are resistant to all available antibiotics. In this review, we identify the mechanisms that P.

A Screen of Natural Product Extracts Identifies Moenomycin as a Potent Antigonococcal Agent.

Increasing multidrug resistance in is a growing public health crisis. Resistance to the last line therapies, cephalosporins and azithromycin, are of particular concern, fueling the need to discover new treatments. Here, we identified the phosphoglycolipid moenomycin from a screen of microbial natural products against drug-resistant as a potent antigonococcal agent.

Speed and strength of an epidemic intervention.

An epidemic can be characterized by its strength (i.e., the reproductive number [Formula: see text]) and speed (i.

Ancient Antibiotics, Ancient Resistance.

As the spread of antibiotic resistance threatens our ability to treat infections, avoiding the return of a preantibiotic era requires the discovery of new drugs. While therapeutic use of antibiotics followed by the inevitable selection of resistance is a modern phenomenon, these molecules and the genetic determinants of resistance were in use by environmental microbes long before humans discovered them. In this review, we discuss evidence that antibiotics and resistance were present in the environment before anthropogenic use, describing techniques including direct sampling of ancient DNA and phylogenetic analyses that are used to reconstruct the past.

COVID-19: Current knowledge in clinical features, immunological responses, and vaccine development.

The COVID-19 pandemic has unfolded to be the most challenging global health crisis in a century. In 11 months since its first emergence, according to WHO, the causative infectious agent SARS-CoV-2 has infected more than 100 million people and claimed more than 2.15 million lives worldwide.

ApmA Is a Unique Aminoglycoside Antibiotic Acetyltransferase That Inactivates Apramycin.

Apramycin is an aminoglycoside antibiotic with the potential to be developed to combat multidrug-resistant pathogens. Its unique structure evades the clinically widespread mechanisms of aminoglycoside resistance that currently compromise the efficacy of other members in this drug class. Of the aminoglycoside-modifying enzymes that chemically alter these antibiotics, only AAC(3)-IVa has been demonstrated to confer resistance to apramycin through -acetylation.

Self-collected oral flocked swabs to measure prevalence of Epstein-Barr Virus antibodies and DNA amongst university students.

Epstein-Barr Virus (EBV) exposure and illness is common in undergraduate university students and may affect academic achievement, social life, and quality of life. We designed a study to measure EBV exposure (EBV-IgG, either Epstein-Barr nuclear antigen 1 (EBNA-1)-IgG or viral capsid antigen (VCA)-IgG) and current viral shedding (EBV-DNA) using self-collected oral swabs among university undergraduate students. Of 184 students enrolled, 129 (70.

Whole genome sequence of isolated from a case of recurrent granulomatous mastitis.

We describe the case of a 33-year-old woman with recurrent granulomatous mastitis associated with This organism has been increasingly associated with granulomatous mastitis, specifically the cystic neutrophilic histopathologic variant, although currently there is a paucity both of reported cases and genomic sequence data. We highlight the challenges in the diagnosis and treatment of this entity, in particular focusing on the various methods of microbiologic identification, including MALDI-TOF, 16 s rRNA PCR and whole-genome sequencing.

Identifying novel β-lactamase substrate activity through prediction of antimicrobial resistance.

Diagnosing antimicrobial resistance (AMR) in the clinic is based on empirical evidence and current gold standard laboratory phenotypic methods. Genotypic methods have the potential advantages of being faster and cheaper, and having improved mechanistic resolution over phenotypic methods. We generated and applied rule-based and logistic regression models to predict the AMR phenotype from and multidrug-resistant clinical isolate genomes.

A Highly Specific DNA Aptamer for RNase H2 from .

Molecular recognition elements with high specificity are of great importance for the study of molecular interactions, accurate diagnostics, drug design, and personalized medicine. Herein, a highly specific DNA aptamer for RNase H2 from () was generated by SELEX and minimized to 40 nucleotides. The aptamer exhibits a dissociation constant () of 1.

Forward-looking serial intervals correctly link epidemic growth to reproduction numbers.

The reproduction number R and the growth rate r are critical epidemiological quantities. They are linked by generation intervals, the time between infection and onward transmission. Because generation intervals are difficult to observe, epidemiologists often substitute serial intervals, the time between symptom onset in successive links in a transmission chain.

Patterns of smallpox mortality in London, England, over three centuries.

Smallpox is unique among infectious diseases in the degree to which it devastated human populations, its long history of control interventions, and the fact that it has been successfully eradicated. Mortality from smallpox in London, England was carefully documented, weekly, for nearly 300 years, providing a rare and valuable source for the study of ecology and evolution of infectious disease. We describe and analyze smallpox mortality in London from 1664 to 1930.

Response to Brinkmann et al. "Re-assembly of 19th century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the United States".

We thank Brinkmann and colleagues for their correspondence and their further investigation into these American Civil War Era vaccination strains. Here, we summarize the difficulties and caveats of work with ancient DNA.

Phage-antibiotic combinations: a promising approach to constrain resistance evolution in bacteria.

Antibiotic resistance has reached dangerously high levels throughout the world. A growing number of bacteria pose an urgent, serious, and concerning threat to public health. Few new antibiotics are available to clinicians and only few are in development, highlighting the need for new strategies to overcome the antibiotic resistance crisis.

Resistance-Guided Discovery of Elfamycin Antibiotic Producers with Antigonococcal Activity.

The rise of bacterial antibiotic resistance coupled with a diminished antibiotic drug pipeline underlines the importance of developing rational strategies to discover new antimicrobials. Microbially derived natural products are the basis for most of the antibiotic arsenal available to modern medicine. Here, we demonstrate a resistance-based approach to identify producers of elfamycins, an under-explored class of natural product antibiotics that target the essential translation factor EF-Tu.

GPAHex-A synthetic biology platform for Type IV-V glycopeptide antibiotic production and discovery.

Glycopeptide antibiotics (GPAs) are essential for the treatment of severe infectious diseases caused by Gram-positive bacteria. The emergence and spread of GPA resistance have propelled the search for more effective GPAs. Given their structural complexity, genetic intractability, and low titer, expansion of GPA chemical diversity using synthetic or medicinal chemistry remains challenging.

Airway Macrophages Mediate Mucosal Vaccine-Induced Trained Innate Immunity against in Early Stages of Infection.

, the causative agent of pulmonary tuberculosis (TB), is responsible for millions of infections and deaths annually. Decades of TB vaccine development have focused on adaptive T cell immunity, whereas the importance of innate immune contributions toward vaccine efficacy has only recently been recognized. Airway macrophages (AwM) are the predominant host cell during early pulmonary infection and, therefore, represent attractive targets for vaccine-mediated immunity.