Perturbation of peptidoglycan recycling by anti-folates and design of a dual-action inhibitor.

Unlabelled: Peptidoglycan (PG) is an important bacterial macromolecule that confers cell shape and structural integrity, and is a key antibiotic target. Its synthesis and turnover are carefully coordinated with other cellular processes and pathways. Despite established connections between the biosynthesis of PG and the outer membrane, or PG and DNA replication, links between PG and folate metabolism remain comparatively unexplored.

Identification of patient demographic, clinical, and SARS-CoV-2 genomic factors associated with severe COVID-19 using supervised machine learning: a retrospective multicenter study.

Background: Drivers of COVID-19 severity are multifactorial and include multidimensional and potentially interacting factors encompassing viral determinants and host-related factors (i.e., demographics, pre-existing conditions and/or genetics), thus complicating the prediction of clinical outcomes for different severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants.

Conference report of the 2024 Antimicrobial Resistance Meeting.

The Antimicrobial Resistance - Genomes, Big Data and Emerging Technologies Conference explored key topics including measuring the burden of AMR, global public health pathogen genomics infrastructure and surveillance, translation and implementation of genomics for AMR control, use of techniques such as wastewater surveillance, mathematical and statistical modelling, and Artificial Intelligence (AI) to aid understanding of AMR. This report describes research presented during plenary sessions and discussions, keynote presentations and posters.

Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial.

Background: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.

Methods: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring©; 7.

Structural conservation and functional role of TfpY-like proteins in type IV pilus assembly.

Unlabelled: Type IV pili (T4P) are important virulence factors that allow bacteria to adhere to and rapidly colonize their hosts. T4P are primarily composed of major pilins that undergo cycles of extension and retraction and minor pilins that initiate pilus assembly. Bacteriophages use T4P as receptors and exploit pilus dynamics to infect their hosts.

Investigation of the Mesencephalic Astrocyte Derived Neurotrophic Factor-Endoplasmic Reticulum Stress Pathway in Mood Disorders.

Background: Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress.

Dereplication of Natural Product Antifungals via Liquid Chromatography-Tandem Mass Spectrometry and Chemical Genomics.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.

Expert consensus on the benefits of neuraminidase in conventional influenza vaccines: a Delphi study.

Background: Seasonal vaccination is the mainstay of human influenza prevention. Licensed influenza vaccines are regularly updated to account for viral mutations and antigenic drift and are standardised for their haemagglutinin content. However, vaccine effectiveness remains suboptimal.

Specialized killing across the domains of life by the type VI secretion systems of Pseudomonas aeruginosa.

Type VI secretion systems (T6SSs) are widespread bacterial protein secretion machines that inject toxic effector proteins into nearby cells, thus facilitating both bacterial competition and virulence. Pseudomonas aeruginosa encodes three evolutionarily distinct T6SSs that each export a unique repertoire of effectors. Owing to its genetic tractability, P.

The Janus Effect: The Biochemical Logic of Antibiotic Resistance.

Antibiotics are essential medicines threatened by the emergence of resistance in all relevant bacterial pathogens. The engagement of the molecular targets of antibiotics offers multiple opportunities for resistance to emerge. Successful target engagement often requires passage of the antibiotic from outside into the cell interior through one or two distinct membrane barriers.

AI Methods for Antimicrobial Peptides: Progress and Challenges.

Antimicrobial peptides (AMPs) are promising candidates to combat multidrug-resistant pathogens. However, the high cost of extensive wet-lab screening has made AI methods for identifying and designing AMPs increasingly important, with machine learning (ML) techniques playing a crucial role. AI approaches have recently revolutionised this field by accelerating the discovery of new peptides with anti-infective activity, particularly in preclinical mouse models.

Revisiting the potential of natural products in antimycobacterial therapy: advances in drug discovery and semisynthetic solutions.

Natural products have been pivotal in treating mycobacterial infections with early antibiotics such as streptomycin, forming the foundation of tuberculosis therapy. However, the emergence of multidrug-resistant and extensively drug-resistant Mycobacterium species has intensified the need for novel antimycobacterial agents. In this review, we revisit the historical contributions of natural products to antimycobacterial drug discovery and highlight recent advances in the field.

Protocol for bacterial filtration efficiency evaluations of facemask materials using viable bacteria-laden aerosol droplets.

Here, we present a protocol for determining the bacterial filtration efficiencies of facemask materials according to the American Society for Testing and Materials (ASTM) standard F2101-19. We describe steps for reproducibly generating, collecting, and enumerating viable bacteria-laden aerosols containing the bacterial pathogen Staphylococcus aureus. The optimized operating parameters generate 1,700 to 3,000 viable bacteria-laden aerosol droplets between 2.

Temperate phage-antibiotic synergy is widespread-extending to -but varies by phage, host strain, and antibiotic pairing.

Unlabelled: Bacteriophages (phages) are bacterial-specific viruses that can be used alone or with antibiotics to reduce bacterial load. Most phages are unsuitable for therapy because they are "temperate" and can integrate into the host genome, forming a lysogen that is protected from subsequent phage infections. However, integrated phages can be awakened by stressors such as antibiotics.

SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL), a Snakemate workflow for rapid and bulk analysis of Illumina sequencing of SARS-CoV-2 genomes.

The incorporation of sequencing technologies in frontline and public health healthcare settings was vital in developing virus surveillance programs during the Coronavirus Disease 2019 (COVID-19) pandemic caused by transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, increased data acquisition poses challenges for both rapid and accurate analyses. To overcome these hurdles, we developed the SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL) for quick bulk analyses of Illumina short-read sequencing data.

CRISPR/RNA Aptamer System Activated by an AND Logic Gate for Biomarker-Driven Theranostics.

The development of an engineered RNA device capable of detecting multiple biomarkers to evaluate pathological states and autonomously implement responsive therapies is urgently needed. Here, we report InCasApt, an integrated nano CRISPR Cas13a/RNA aptamer theranostic platform capable of achieving both biomarker detection and biomarker-driven therapy. Within this system, a Cas13a/crRNA complex, a hairpin reporter (HR), a dinitroaniline caged Ce6 photosensitizer (Ce6-DN), and a DN-binding RNA aptamer precursor (DNBApt) are coloaded onto dendritic mesoporous silicon nanoparticles (DMSN) in a controlled manner.

Skin-associated shares cobamides.

Unlabelled: The underlying interactions that occur to maintain skin microbiome composition, function, and overall skin health are largely unknown. Often, these types of interactions are mediated by microbial metabolites. Cobamides, the vitamin B family of cofactors, are essential for metabolism in many bacteria but are only synthesized by a fraction of prokaryotes, including certain skin-associated species.

Multi-conflict islands are a widespread trend within Serratia spp.

Bacteria carry numerous anti-phage systems in "defense islands" or hotspots. Recent studies have delineated the content and boundaries of these islands in various species, revealing instances of islands that encode additional factors, including antibiotic resistance genes, stress genes, type VI secretion system (T6SS)-dependent effectors, and virulence factors. Our study identifies three defense islands in the Serratia genus with a mixed cargo of anti-phage systems, virulence factors, and different types of anti-bacterial modules, revealing a widespread trend of co-accumulation that extends beyond T6SS-dependent effectors to colicins and contact-dependent inhibition systems.

Examining the molecular clock hypothesis for the contemporary evolution of the rabies virus.

The molecular clock hypothesis assumes that mutations accumulate on an organism's genome at a constant rate over time, but this assumption does not always hold true. While modelling approaches exist to accommodate deviations from a strict molecular clock, assumptions about rate variation may not fully represent the underlying evolutionary processes. There is considerable variability in rabies virus (RABV) incubation periods, ranging from days to over a year, during which viral replication may be reduced.

A widespread accessory protein family diversifies the effector repertoire of the type VI secretion system spike.

Type VI secretion systems (T6SSs) are macromolecular assemblies that deliver toxic effector proteins between adjacent bacteria. These effectors span a wide range of protein families that all lack canonical signal sequences that would target them for export. Consequently, it remains incompletely understood how conserved structural components of the T6SS apparatus recognize a diverse repertoire of effectors.

The antibacterial activity of a prophage-encoded fitness factor is neutralized by two cognate immunity proteins.

The human gastrointestinal tract is a competitive environment inhabited by dense polymicrobial communities. Bacteroides, a genus of Gram-negative anaerobes, are prominent members of this ecological niche. Bacteroides spp.

Early-life upper airway microbiota are associated with decreased lower respiratory tract infections.

Background: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.

Objectives: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.