Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 μg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fungal cells. F4a and indolin-3-one combined with bioAgNP exhibited synergistic fungicidal activity against planktonic cells. F4a, alone or combined with bioAgNP, also caused a significant decrease in the number of viable cells within the biofilms. No cytotoxicity to mammalian cells was detected for bacterial metabolites combined with bioAgNP at synergistic concentrations that presented antifungal activity. These results indicate the potential of F4a combined with bioAgNP as a new strategy for controlling C. auris infections.

COVID-19, a disease caused by SARS-CoV-2, was declared a pandemic in 2020 and created a global crisis in health systems, with more than 545 million confirmed cases and 6.33 million deaths. In this sense, this work aims to identify possible inhibitors of the SARS-CoV-2 RdRp enzyme using in silico approaches. RdRp is a crucial enzyme in the replication and assembly cycle of new viral particles and a critical pharmacological target in the treatment of COVID-19. We performed a virtual screening based on molecular docking from our in-house chemical library, which contains a diversity of 313 structures from different chemical classes. Nine compounds were selected since they showed important interactions with the active site from RdRp. Next, the ADME-Tox in silico predictions served as a filter and selected the three most promising compounds: a coumarin LMed-052, a hydantoin LMed-087, and a guanidine LMed-250. Molecular dynamics simulations revealed details such as changes in the positions of ligands and catalytic residues during the simulations compared to the complex from molecular docking studies. Binding free energy analysis was performed using the MMGBSA method, demonstrating that LMed-052 and LMed-087 have better affinities for the RdRp by energetic contributions to the stability of the complexes when compared to LMed-250. Furthermore, LMed-052 showed significant in vitro inhibition against MHV-3, decreasing 99% of viral titers. Finally, these findings are useful to guide structural modifications aiming to improve the potential of these compounds to act as inhibitors of SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Since ancient times, plants have been used in folk medicine to treat different diseases. Plants offer exceptional chemical diversity with a wide range of biological activities, and have therefore been the most promising sources for the discovery and development of drugs, including antimicrobial agents. This study reports the antibacterial effect of geraniol (GER), alone and in combination with biogenic silver nanoparticles (bioAgNPs), produced using the aqueous extract of Trichilia catigua bark, against planktonic and sessile cells of methicillin-resistant Staphylococcus aureus (MRSA), one of the main opportunistic and potentially fatal human pathogens. GER had a time-dependent bactericidal effect on planktonic cells, impairing the cell membrane integrity. In addition, GER inhibited the staphyloxanthin production, and molecular docking analyses supported the in silico affinity of GER to dehydrosqualene synthase (CrtM) and 4,4′-diaponeurosporen-aldehyde dehydrogenase (AldH), which are key enzymes within the pigment biosynthesis pathway in S. aureus. GER treatment increased the sensitivity of MRSA to hydrogen peroxide killing. GER displayed synergism with bioAgNPs against planktonic and sessile cells, inhibiting bacterial adhesion and the viability of biofilms formed on abiotic surfaces. MRSA planktonic and sessile cells treated with GER or GER/bioAgNPs displayed severe morphological and ultrastructural alterations. Notably, neither GER nor its combination caused in vitro and in vivo toxicity in mammalian cells and Galleria mellonella larvae, respectively. These findings suggest that the combination of GER/bioAgNPs may be a promising strategy to control MRSA infections.

Candida tropicalis is regarded as an opportunistic pathogen, causing diseases ranging from superficial infections to life-threatening disseminated infections. The ability of this yeast to form biofilms and develop resistance to antifungals represents a significant therapeutic challenge. Herein, the effect of geraniol (GER), alone and combined with fluconazole (FLZ), was evaluated in the planktonic and sessile cells of azole-resistant C. tropicalis. GER showed a time-dependent fungicidal effect on the planktonic cells, impairing the cell membrane integrity. Additionally, GER inhibited the rhodamine 6G efflux, and the molecular docking analyzes supported the binding affinity of GER to the C. tropicalis Cdr1 protein. GER exhibited a synergism with FLZ against the planktonic and sessile cells, inhibiting the adhesion of the yeast cells and the viability of the 48-h biofilms formed on abiotic surfaces. C. tropicalis biofilms treated with GER, alone or combined with FLZ, displayed morphological and ultrastructural alterations, including a decrease in the stacking layers and the presence of wilted cells. Moreover, neither GER alone nor combined with FLZ caused toxicity, and both treatments prolonged the survival of the Galleria mellonella larvae infected with azole-resistant C. tropicalis. These findings indicate that the combination of GER and FLZ may be a promising strategy to control azole-resistant C. tropicalis infections.

Background/Objectives: Burn injuries represent a global public health concern, accounting for approximately 265,000 deaths annually and often leading to severe infections. With the increasing prevalence of multidrug-resistant (MDR) bacteria, innovative therapeutic strategies such as nanoparticle-based topical formulations have gained attention. This study proposed the development of a hydrogel for burn treatment containing biogenic silver nanoparticles (BioAgNPs), hyaluronic acid (HA), and allantoin (AL). Methods: BioAgNPs were previously characterized by transmission electron microscopy (TEM) and incorporated into a hydrogel containing HA and AL, which was physicochemically characterized by pH, spreadability, and energy-dispersive X-ray spectroscopy (EDX). Antibacterial activity was evaluated by broth microdilution, agar diffusion, and time–kill assays against standard and MDR bacterial strains. Cytotoxicity was assessed using the MTT assay in L929 cells, and wound-healing potential was investigated through an in vitro scratch assay to evaluate cell migration and proliferation. Results: BioAgNPs exhibited antibacterial activity against reference strains and MDR isolates, determining the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). HA and AL were non-toxic, while BioAgNPs demonstrated low cytotoxic activity. Although HA and AL did not exhibit antibacterial properties, they promoted cell migration and proliferation. The formulation exhibited physicochemical and pharmaceutical stability, showing suitable properties for topical use, and presented significant antimicrobial action, with bacterial elimination occurring within 2 h of contact, except for S. aureus. Conclusions: Thus, the hydrogel presents a promising alternative for the topical treatment of infected burns, with potential application in combating multidrug-resistant bacteria, being able to eliminate MDR Acinetobacter baumannii.

Plants are a valuable source of bioactive compounds with therapeutic potential. Antibacterials of natural origin represent a promising and sustainable alternative in the fight against bacterial infections. In addition to being effective against bacterial growth, these natural agents may have lower toxicity and fewer side effects, which reinforces their value in the development of new therapeutic strategies. This study reports on the antibacterial effect of eugenol (EUG) and biogenic silver nanoparticles (bioAgNPs) synthesized using the aqueous extract of Trichilia catigua A. Juss. bark, alone or in combination, against planktonic and sessile cells of multidrug-resistant Staphylococcus pseudintermedius, one of the main opportunistic pathogens in dogs. EUG and bioAgNPs showed a dose- and time-dependent bactericidal effect on planktonic cells, interfering with cell membrane integrity. The interaction between EUG and bioAgNPs was classified as synergistic or indifferent for planktonic cells. Except for one isolate, the combination exhibited a synergistic effect for biofilms previously formed on abiotic surfaces for 24 h. Both bioactive compounds promoted morphological and ultrastructural changes in S. pseudintermedius biofilms. All concentrations of EUG and bioAgNPs in synergistic or indifferent combinations showed reduced toxicity to mammalian cells. These findings suggest that the EUG and bioAgNP combination could be a promising strategy for controlling S. pseudintermedius infections.