SARS-CoV-2, Early Entry Events.

Viruses are obligate intracellular parasites, and host cell entry is the first step in the viral life cycle. The SARS-CoV-2 (COVID-19) entry process into susceptible host tissue cells is complex requiring (1) attachment of the virus via the conserved spike (S) protein receptor-binding motif (RBM) to the host cell angiotensin-converting-enzyme 2 (ACE2) receptor, (2) S protein proteolytic processing, and (3) membrane fusion. Spike protein processing occurs at two cleavage sites, i.

Pirfenidone regulates LPS mediated activation of neutrophils.

Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing.

Beyond the Nanomaterials Approach: Influence of Culture Conditions on the Stability and Antimicrobial Activity of Silver Nanoparticles.

Silver nanoparticles (AgNPs) as antimicrobial agents have been extensively studied. It is generally assumed that their inhibitory activity heavily depends on their physicochemical features. Yet, other parameters may affect the AgNP traits and activity, such as culture medium composition, pH, and temperature, among others.

Interactions of FK506 and Rapamycin With FK506 Binding Protein 12 in Opportunistic Human Fungal Pathogens.

Over the past few decades advances in modern medicine have resulted in a global increase in the prevalence of fungal infections. Particularly people undergoing organ transplants or cancer treatments with a compromised immune system are at an elevated risk for lethal fungal infections such as invasive candidiasis, aspergillosis, cryptococcosis, etc. The emergence of drug resistance in fungal pathogens poses a serious threat to mankind and it is critical to identify new targets for the development of antifungals.

Inhibition of Mixed Biofilms of and Methicillin-Resistant by Positively Charged Silver Nanoparticles and Functionalized Silicone Elastomers.

Both bacterial and fungal organisms display the ability to form biofilms; however, mixed bacterial/fungal biofilms are particularly difficult to control and eradicate. The opportunistic microbial pathogens and are among the most frequent causative agents of healthcare-acquired infections, and are often co-isolated forming mixed biofilms, especially from contaminated catheters. These mixed species biofilms display a high level of antibiotic resistance; thus, these infections are challenging to treat resulting in excess morbidity and mortality.

Silver Nanoantibiotics Display Strong Antifungal Activity Against the Emergent Multidrug-Resistant Yeast Under Both Planktonic and Biofilm Growing Conditions.

is an emergent multidrug-resistant pathogenic yeast with an unprecedented ability for a fungal organism to easily spread between patients in clinical settings, leading to major outbreaks in healthcare facilities. The formation of biofilms by contributes to infection and its environmental persistence. Most antifungals and sanitizing procedures are not effective against , but antimicrobial nanomaterials could represent a viable alternative to combat the infections caused by this emerging pathogen.

Molecular Effects of Silver Nanoparticles on Monogenean Parasites: Lessons from .

The mechanisms of action of silver nanoparticles (AgNPs) in monogenean parasites of the genus were investigated through a microarray hybridization approach using genomic information from the nematode . The effects of two concentrations of AgNPs were explored, low (6 µg/L Ag) and high (36 µg/L Ag). Microarray analysis revealed that both concentrations of AgNPs activated similar biological processes, although by different mechanisms.

Bismuth Nanoantibiotics Display Anticandidal Activity and Disrupt the Biofilm and Cell Morphology of the Emergent Pathogenic Yeast .

is an emergent multidrug-resistant pathogenic yeast, which forms biofilms resistant to antifungals, sanitizing procedures, and harsh environmental conditions. Antimicrobial nanomaterials represent an alternative to reduce the spread of pathogens-including yeasts-regardless of their drug-resistant profile. Here we have assessed the antimicrobial activity of easy-to-synthesize bismuth nanoparticles (BiNPs) against the emergent multidrug-resistant yeast , under both planktonic and biofilm growing conditions.

Short-term effects of MnO nanoparticles on physiological activities and gene expression of nitrifying bacteria under low and high dissolved oxygen conditions.

The short-term effects of MnO nanoparticles (NPs) were examined for nitrifying bacterial enrichments exposed under low and high dissolved oxygen (DO) conditions using substrate (ammonia) specific oxygen uptake rates (sOUR), reverse transcriptase - quantitative polymerase chain reaction (RT-qPCR) assays, and by analysis of 16S rRNA sequences. Samples from nitrifying bioreactor were exposed in batch vessels to MnO NPs (1, 5 and 10 mg/L) for either 1 or 3 h under no additional aeration or 0.25 L/min aeration.

Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy.

Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi are eukaryotic organisms and, as such, there is a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted in a very restricted number of antifungal drugs that are clinically available for the treatment of invasive fungal infections at the present time-polyenes, azoles, echinocandins, and flucytosine.

Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity.

Fungal organisms are ubiquitous in nature, and progress of modern medicine is creating an expanding number of severely compromised patients susceptible to a variety of opportunistic fungal infections. These infections are difficult to diagnose and treat, leading to high mortality rates. The limited antifungal arsenal, the toxicity of current antifungal drugs, the development of resistance, and the emergence of new multidrug-resistant fungi, all highlight the urgent need for new antifungal agents.

FDA Approved Drug Library Screening Identifies Robenidine as a Repositionable Antifungal.

Due to the increasing prevalence of pathogenic fungal infections, the emergence of antifungal resistant clinical isolates worldwide, and the limited arsenal of available antifungals, developing new antifungal strategies is imperative. In this study, we screened a library of 1068 FDA-approved drugs to identify hits that exhibit broad-spectrum antifungal activity. Robenidine, an anticoccidial agent which has been widely used to treat coccidian infections of poultry and rabbits, was identified in this screen.

The heterotrimeric G-protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungus Mucor circinelloides.

Mucor circinelloides, a dimorphic opportunistic pathogen, expresses three heterotrimeric G-protein beta subunits (Gpb1, Gpb2 and Gpb3). The Gpb1-encoding gene is up-regulated during mycelial growth compared with that in the spore or yeast stage. gpb1 deletion mutation analysis revealed its relevance for an adequate development during the dimorphic transition and for hyphal growth under low oxygen concentrations.

Manipulation of the Plant Host by the Geminivirus AC2/C2 Protein, a Central Player in the Infection Cycle.

Geminiviruses are a significant group of emergent plant DNA viruses causing devastating diseases in food crops worldwide, including the Southern United States, Central America and the Caribbean. Crop failure due to geminivirus-related disease can be as high as 100%. Improved global transportation has enhanced the spread of geminiviruses and their vectors, supporting the emergence of new, more virulent recombinant strains.

Fast, facile synthesis method for BAL-mediated PVP-bismuth nanoparticles.

Bismuth is a water-insoluble non-toxic metallic element used in a wide array of pharmaceutical products, cosmetics, and catalysts, among others. Yet, the research regarding the use of bismuth nanoparticles (BiNPs) for antimicrobial treatments is scarce. Most of the current protocols for synthesizing BiNPs suitable for medical uses cannot be easily replicated in non-specialized laboratories.

CARD9-Associated Dectin-1 and Dectin-2 Are Required for Protective Immunity of a Multivalent Vaccine against Infection.

species are fungal pathogens that can cause a widely varied clinical manifestation from mild pulmonary symptom to disseminated, life-threatening disease. We have previously created a subunit vaccine by encapsulating a recombinant coccidioidal Ag (rCpa1) in glucan-chitin particles (GCPs) as an adjuvant-delivery system. The GCP-rCpa1 vaccine has shown to elicit a mixed Th1 and Th17 response and confers protection against pulmonary coccidioidomycosis in mice.

Pathogenomes of Atypical Non-shigatoxigenic NSF/SF O157:H7/NM: Comprehensive Phylogenomic Analysis Using Closed Genomes.

The toxigenic conversion of strains by Shiga toxin-converting (Stx) bacteriophages were prominent and recurring events in the stepwise evolution of enterohemorrhagic (EHEC) O157:H7 from an enteropathogenic (EPEC) O55:H7 ancestor. Atypical, attenuated isolates have been described for both non-sorbitol fermenting (NSF) O157:H7 and SF O157:NM serotypes, which are distinguished by the absence of Stx, the characteristic virulence hallmark of Stx-producing (STEC). Such atypical isolates either never acquired Stx-phages or may have secondarily lost during the course of infection, isolation, or routine subculture; the latter are commonly referred to as LST (Lost Shiga Toxin)-isolates.

The Role of MicroRNA-155 in Chlamydia muridarum Infected lungs.

Our laboratory has investigated the role of an evolutionarily conserved RNA species called microRNAs (miRs) in regulation of anti-chlamydial protective immunity. MiRs including miR-155 expressed in specific immune effector cells are critical for antigen specific protective immunity and IFN-γ production. Using miR-155 deficient mice, and a murine pulmonary model for chlamydial infection, we report here 1) the effect of host miR-155 on bacterial burden, and 2) identify probable immune genes regulated by miR-155.

A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides.

Mucormycosis is an emerging lethal fungal infection in immunocompromised patients. is a causal agent of mucormycosis and serves as a model system to understand genetics in Mucorales. Calcineurin is a conserved virulence factor in many pathogenic fungi, and calcineurin inhibition or deletion of the calcineurin regulatory subunit (CnbR) in results in a shift from hyphal to yeast growth.

mSphere of Influence: the Mycobiota in Human Health and Disease.

Soo Chan Lee works in the field of medical mycology. In this mSphere of Influence article, he reflects on how "Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis" (Science 336:1314-1317, 2012, https://doi.org/10.

Inhibition of Biofilm Formation on Medical and Environmental Surfaces by Silver Nanoparticles.

is an emerging pathogenic fungus implicated in healthcare-associated outbreaks and causes bloodstream infections associated with high mortality rates. Biofilm formation represents one of the major pathogenetic traits associated with this microorganism. Unlike most other species, has the ability to survive for weeks on different surfaces.

Thioredoxin Modulates Cell Surface Hydrophobicity in .

, a Gram-negative coccobacillus, has become a prevalent nosocomial health threat affecting the majority of hospitals both in the U.S. and around the globe.

CARD9 Is Required for Classical Macrophage Activation and the Induction of Protective Immunity against Pulmonary Cryptococcosis.

Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against , an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients.

Activating a Silver Lipoate Nanocluster with a Penicillin Backbone Induces a Synergistic Effect against Biofilm.

Many antibiotic resistances to penicillin have been reported, making them obsolete against multiresistant bacteria. Because penicillins act by inhibiting cell wall production while silver particles disrupt the cell wall directly, a synergetic effect is anticipated when both modes of action are incorporated into a cluster. To test this hypothesis, the lipoate ligands (LA) of a silver cluster (Ag) of known composition (AgLA) were covalently conjugated to 6-aminopenicillanic acid, a molecule with a β-lactam backbone.