Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the β-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including Candida and Aspergillus spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the FKS genes, primarily FKS2 mutations in Nakaseomyces glabrata. In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating Pneumocystis jirovecii infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in C. auris infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.
Porphyromonas gingivalis uses a variety of mechanisms to actively interact with and promote the hydrolysis of red blood cells (RBCs) to obtain iron in the form of heme. In this study, we investigated the function of lipoprotein PG1881 which was previously shown to be up-regulated during subsurface growth and selectively enriched on outer membrane vesicles (OMVs). Our results show that wildtype strain W83 formed large aggregates encompassing RBCs whereas the PG1881 deletion mutant remained predominately as individual cells. Using a PG1881 antibody, immunofluorescence revealed that the wildtype strain's aggregation to RBCs involves an extracellular matrix enriched with PG1881. Our findings discover that RBCs elicit cell aggregation and matrix formation by P. gingivalis and that this process is promoted by an OMV-specific lipoprotein. We propose this strategy is advantageous for nutrient acquisition as well as dissemination from the oral cavity and survival of this periodontal pathogen.
The use of plant growth-promoting bacteria as bioinoculants is a powerful tool to increase crop yield and quality and to improve nitrogen use efficiency (NUE) from fertilizers in plants. This study aimed to bioprospecting a native bacterial consortium (Bacillus cabrialesii subsp. cabrialesii TE3T, Priestia megaterium TRQ8, and Bacillus paralicheniformis TRQ65), through bioinformatic analysis, and to quantify the impact of its inoculation on NUE (measured through 15N-isotopic techniques), grain yield, and grain quality of durum wheat variety CIRNO C2008 grown under three doses of urea (0, 120, and 240 kg N ha−1) during two consecutive agricultural cycles in the Yaqui Valley, Mexico. The inoculation of the bacterial consortium (BC) to the wheat crop, at a total N concentration of 123–225 kg N ha−1 increased crop productivity and maintained grain quality, resulting in a yield increase of 1.1 ton ha−1 (6.0 vs. 7.1 ton ha−1, 0 kg N ha−1 added, 123 kg N ha−1 in the soil) and of 2.0 ton ha−1 (5.9 vs. 7.9 ton ha−1, 120 kg N ha−1 added, 104 kg N ha−1 in the soil) compared to the uninoculated controls at the same doses of N. The genomic bioinformatic analysis of the studied strains showed a great number of biofertilization-related genes regarding N and Fe acquisition, P assimilation, CO2 fixation, Fe, P, and K solubilization, with important roles in agroecosystems, as well as genes related to the production of siderophores and stress response. A positive effect of the BC on NUE at the studied initial N content (123 and 104 kg N ha−1) was not observed. Nevertheless, increases of 14 % and 12.5 % on NUE (whole plant) were observed when 120 kg N ha−1 was applied compared to when wheat was fully fertilized (240 kg N ha−1). This work represents a link between bioinformatic approaches of a native bacterial inoculant and the quantification of its impact on durum wheat.
Due to an increase in industrialization and urbanization, massive amounts of solid waste biomass are speedily accumulating in our environment, which poses several adverse effects on habitat and human health thus becoming a matter of discussion in the environmental community. With reference to the circular economy, continuous efforts have been put forward for setting up an organised management approach in combination with an efficient treatment technique for increasing the profitable utilization of solid waste. This review aims to provide a systematic discussion on the recent thermochemical technologies employed for converting waste biomass generated from different sources into valuable products like biochar, bio-oil, heat, energy and syngas. The article further focuses on a few important aspects of thermochemical conversion of waste biomass to useful products like technical factors affecting thermochemical processes, applications of by-products of thermochemical conversion, and biological pretreatment of waste biomass. The review assists interesting recent and scientific trends for boosting up the systematic management and valorization of solid waste through low-cost, efficient, environment-friendly and sustainable technologies.
Candida fungi exploit various virulence strategies to invade the human host, while host cells employ diverse mechanisms to maintain homeostasis and respond to infection. Extracellular vesicles (EVs) are integral components of the multifaceted landscape of host-pathogen interactions, with their abundant production by all contributors involved in these complex and dynamic relations. Herein, we present the current state of knowledge regarding the host response by releasing EVs in reaction to Candida, as well as the influence of fungal EVs on the functionality of the confronted host cells. Fungal vesicles contribute to enhanced adhesion of pathogens to human cells as evidenced for C. auris, and may modulate the production of several cytokines, including IL-6, IL-8, IL-10, IL-12p40, TGF-β and TNF-α, thereby exerting pro-infective and pro-inflammatory effects, as described for C. albicans and other Candida species. Whereas the biosynthesis of EVs by host cells can dynamically modulate the proliferation and viability of fungal cells and affect the candidacidal functionality of other effector cells. The reciprocal influence of EVs from host cells and Candida pathogens is a key focus, explaining their significant role in cell signaling and interkingdom communication.
The present study aimed to isolate a bioflocculating fungal strain from wastewater collected from a local bike garage. The isolate showed maximum similarity to Aspergillus species. The fungus was identified as Aspergillus flavus species F_GTAF1 IU (accession no OP703382). The isolated fungus was evaluated in terms of biomass recovery efficiency in Scenedesmus Sp. GTAF01. The extent of algal fungal co-pelletization was evaluated as a function of the algae-to-fungi ratio, volume of fungal culture in broth, agitation rate, and pH. results showed that at fungal culture volume of 60%v/v, fungal culture volume of 1:3%w/w, 100 rpm, and pH 3, 93.6% biomass was obtained during the initial 5 h. At wavenumbers 1384 and 1024 cm-1 a significant alteration in the transmission percentage was observed in co-pellet compared to algae and fungal cells. This shows the significant role of C-H–H and C-N stretches in co-pellet formation. This study provides deep insight into effective microalgal harvesting along with the simultaneous extraction of lipids that can be used for the sustainable production of biodiesel.