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Scientific Reports Oct 2022The development of bio-based products has increased in recent years, and species of the Bacillus genus have been widely used for product development due to their...
The development of bio-based products has increased in recent years, and species of the Bacillus genus have been widely used for product development due to their elevated production of antimicrobial molecules and resistance to extreme environmental conditions through endospore formation. In this context, the antifungal potential of Bacillus velezensis CMRP 4489 was investigated using in silico predictions of secondary metabolites in its genome and in vitro tests against the following phytopathogenic fungi: Sclerotinia sclerotiorum, Macrophomina phaseolina, and Botrytis cinerea. The in-silico predictions indicated that CMRP 4489 possesses several Biosynthetic Gene Clusters (BGCs) capable of producing molecules with antifungal properties and other non-identified BGCs. The in vitro assay results evidenced strong antifungal activity, inhibiting more than 60% of the tested fungi, and the isolate's molecules were stable under diverse physicochemical conditions. The in vitro assay evidenced significant antifungal activity, deformation of the hyphal structure in SS, biofilm formation capacity, and swarming motility. In the colonization assay, we observed attachment, colonization, and net-shaped biofilm formation, with the strain transitioning from the seeds to nearby structures. Therefore, CMRP 4489 showed to be a potential biocontrol agent against various diseases with agronomic importance and can be used under adverse environmental conditions.
Topics: Antifungal Agents; Biological Control Agents; Bacillus; Anti-Infective Agents; Genomics; Plant Diseases
PubMed: 36257999
DOI: 10.1038/s41598-022-22380-0 -
FEMS Microbiology Reviews Sep 2019The incidence of opportunistic yeast infections in humans has been increasing over recent years. These infections are difficult to treat and diagnose, in part due to the... (Review)
Review
The incidence of opportunistic yeast infections in humans has been increasing over recent years. These infections are difficult to treat and diagnose, in part due to the large number and broad diversity of species that can underlie the infection. In addition, resistance to one or several antifungal drugs in infecting strains is increasingly being reported, severely limiting therapeutic options and showcasing the need for rapid detection of the infecting agent and its drug susceptibility profile. Current methods for species and resistance identification lack satisfactory sensitivity and specificity, and often require prior culturing of the infecting agent, which delays diagnosis. Recently developed high-throughput technologies such as next generation sequencing or proteomics are opening completely new avenues for more sensitive, accurate and fast diagnosis of yeast pathogens. These approaches are the focus of intensive research, but translation into the clinics requires overcoming important challenges. In this review, we provide an overview of existing and recently emerged approaches that can be used in the identification of yeast pathogens and their drug resistance profiles. Throughout the text we highlight the advantages and disadvantages of each methodology and discuss the most promising developments in their path from bench to bedside.
Topics: Antifungal Agents; Drug Resistance, Multiple, Fungal; High-Throughput Nucleotide Sequencing; Humans; Mycoses; Pathology, Molecular; Point-of-Care Systems; Polymerase Chain Reaction; Proteomics; Whole Genome Sequencing; Yeasts
PubMed: 31158289
DOI: 10.1093/femsre/fuz015 -
Frontiers in Cellular and Infection... 2022Fungal populations are commonly found in natural environments and present enormous health care challenges, due to increased resistance to antifungal agents. Paeonol...
Fungal populations are commonly found in natural environments and present enormous health care challenges, due to increased resistance to antifungal agents. Paeonol exhibits antifungal activities; nevertheless, the antifungal and antibiofilm activities of paeonol against and remain largely unexplored. Here, we aimed to evaluate the antifungal and antibiofilm activities of paeonol against and/or (i.e., against mono- or dual-species). The minimum inhibitory concentrations (MICs) of paeonol for mono-species comprising or were 250 μg ml, whereas the MIC values of paeonol for dual-species were 500 μg ml. Paeonol disrupted cell membrane integrity and increased the influx of gatifloxacin into cells of mono- and dual-species cells, indicating an antifungal mode of action. Moreover, paeonol at 8 times the MIC damaged mono- and dual-species cells within and biofilms, as it did planktonic cells. In particular, at 4 and 8 mg ml, paeonol efficiently dispersed preformed 48-h biofilms formed by mono- and dual-species cells, respectively. Paeonol inhibited effectively the yeast-to-hyphal-form transition of and impaired capsule and melanin production of . The addition of 10 MIC paeonol to the medium did not shorten the lifespan of , and 2 MIC paeonol could effectively protect the growth of and -infected . Furthermore, RNA sequencing was employed to examine the transcript profiling of and biofilm cells in response to 1/2 MIC paeonol. RNA sequencing data revealed that paeonol treatment impaired biofilm formation of by presumably downregulating the expression level of initial filamentation, adhesion, and growth-related genes, as well as biofilm biosynthesis genes, whereas paeonol inhibited biofilm formation of by presumably upregulating the expression level of ergosterol biosynthesis-related genes. Together, the findings of this study indicate that paeonol can be explored as a candidate antifungal agent for combating serious single and mixed infections caused by and .
Topics: Acetophenones; Animals; Antifungal Agents; Biofilms; Caenorhabditis elegans; Candida albicans; Cryptococcosis; Cryptococcus neoformans; Microbial Sensitivity Tests
PubMed: 35669114
DOI: 10.3389/fcimb.2022.884793 -
Trends in Pharmacological Sciences Mar 2023Up to 1.5 million people die yearly from fungal disease, but the repertoire of antifungal drug classes is minimal and the incidence of drug resistance is rising rapidly.... (Review)
Review
Up to 1.5 million people die yearly from fungal disease, but the repertoire of antifungal drug classes is minimal and the incidence of drug resistance is rising rapidly. This dilemma was recently declared by the World Health Organization as a global health emergency, but the discovery of new antifungal drug classes remains excruciatingly slow. This process could be accelerated by focusing on novel targets, such as G protein-coupled receptor (GPCR)-like proteins, that have a high likelihood of being druggable and have well-defined biology and roles in disease. We discuss recent successes in understanding the biology of virulence and in structure determination of yeast GPCRs, and highlight new approaches that might pay significant dividends in the urgent search for novel antifungal drugs.
Topics: Humans; Antifungal Agents; Mycoses; Receptors, G-Protein-Coupled
PubMed: 36801017
DOI: 10.1016/j.tips.2022.12.002 -
Antimicrobial Agents and Chemotherapy Jan 2021Fungal infections are a universal problem and are routinely associated with high morbidity and mortality rates in immunocompromised patients. Existing therapies comprise... (Review)
Review
Fungal infections are a universal problem and are routinely associated with high morbidity and mortality rates in immunocompromised patients. Existing therapies comprise five different classes of antifungal agents, four of which target the synthesis of ergosterol and cell wall glucans. However, the currently available antifungals have many limitations, including poor oral bioavailability, narrow therapeutic indices, and emerging drug resistance resulting from their use, thus making it essential to investigate the development of novel drugs which can overcome these limitations and add to the antifungal armamentarium. Advances have been made in antifungal drug discovery research and development over the past few years as evidenced by the presence of several new compounds currently in various stages of development. In the following minireview, we provide a comprehensive summary of compounds aimed at one or more novel molecular targets. We also briefly describe potential pathways relevant for fungal pathogenesis that can be considered for drug development in the near future.
Topics: Antifungal Agents; Drug Discovery; Ergosterol; Fungi; Humans; Mycoses
PubMed: 33229427
DOI: 10.1128/AAC.01719-20 -
Environmental Science and Pollution... Feb 2023Humans are exposed to the variety of emerging environmental pollutant in everyday life. The special concern is paid to endocrine disrupting chemicals especially to... (Review)
Review
Humans are exposed to the variety of emerging environmental pollutant in everyday life. The special concern is paid to endocrine disrupting chemicals especially to triclosan which could interfere with normal hormonal functions. Triclosan could be found in numerous commercial products such as mouthwashes, toothpastes and disinfectants due to its antibacterial and antifungal effects. Considering the excessive use and disposal, wastewaters are recognized as the main source of triclosan in the aquatic environment. As a result of the incomplete removal, triclosan residues reach surface water and even groundwater. Triclosan has potential to accumulate in sediment and aquatic organisms. Therefore, the detectable concentrations of triclosan in various environmental and biological matrices emerged concerns about the potential toxicity. Triclosan impairs thyroid homeostasis and could be associated with neurodevelopment impairment, metabolic disorders, cardiotoxicity and the increased cancer risk. The growing resistance of the vast groups of bacteria, the evidenced toxicity on different aquatic organisms, its adverse health effects observed in vitro, in vivo as well as the available epidemiological studies suggest that further efforts to monitor triclosan toxicity at environmental levels are necessary. The safety precaution measures and full commitment to proper legislation in compliance with the environmental protection are needed in order to obtain triclosan good ecological status. This paper is an overview of the possible negative triclosan effects on human health. Sources of exposure to triclosan, methods and levels of detection in aquatic environment are also discussed.
Topics: Humans; Triclosan; Risk; Disinfectants; Antifungal Agents; Aquatic Organisms; Outcome Assessment, Health Care; Water Pollutants, Chemical
PubMed: 34741734
DOI: 10.1007/s11356-021-17273-0 -
BioMed Research International 2022Plant viruses are the most destructive pathogens which cause devastating losses to crops due to their diversity in the genome, rapid evolution, mutation or recombination... (Review)
Review
Plant viruses are the most destructive pathogens which cause devastating losses to crops due to their diversity in the genome, rapid evolution, mutation or recombination in the genome, and lack of management options. It is important to develop a reliable remedy to improve the management of plant viral diseases in economically important crops. Some reports show the efficiency of metal nanoparticles and engineered nanomaterials and their wide range of applications in nanoagriculture. Currently, there are reports for the use of nanoparticles as an antibacterial and antifungal agent in plants and animals too, but few reports as plant antiviral. "Nanophytovirology" has been emerged as a new branch that covers nanobased management approaches to deal with devastating plant viruses. Varied nanoparticles have specific physicochemical properties that help them to interact in various unique and useful ways with viruses and their vectors along with the host plants. To explore the antiviral role of nanoparticles and for the effective management of plant viruses, it is imperative to understand all minute details such as the concentration/dosage of nanoparticles, time of application, application interval, and their mechanism of action. This review focused on different aspects of metal nanoparticles and metal oxides such as their interaction with plant viruses to explore the antiviral role and the multidimensional perspective of nanotechnology in plant viral disease detection, treatment, and management.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Antiviral Agents; Metal Nanoparticles; Nanotechnology; Oxides; Plant Viruses; Plants
PubMed: 36225980
DOI: 10.1155/2022/8688584 -
Frontiers in Immunology 2022Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African... (Review)
Review
Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, , is only partially understood. IFNγ producing CD4 T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa.
Topics: Antifungal Agents; Central Nervous System Fungal Infections; Cryptococcosis; Cryptococcus neoformans; HIV Infections; Humans; Meningitis, Cryptococcal
PubMed: 35432326
DOI: 10.3389/fimmu.2022.804674 -
Molecules (Basel, Switzerland) Apr 2023The 1,2,3-dithiazole is an underappreciated scaffold in medicinal chemistry despite possessing a wide variety of nascent pharmacological activities. The scaffold has a... (Review)
Review
The 1,2,3-dithiazole is an underappreciated scaffold in medicinal chemistry despite possessing a wide variety of nascent pharmacological activities. The scaffold has a potential wealth of opportunities within these activities and further afield. The 1,2,3-dithiazole scaffold has already been reported as an antifungal, herbicide, antibacterial, anticancer agent, antiviral, antifibrotic, and is a melanin and Arabidopsis gibberellin 2-oxidase inhibitor. These structure activity relationships are discussed in detail, along with insights and future directions. The review also highlights selected synthetic strategies developed towards the 1,2,3-dithiazole scaffold, how these are integrated to accessibility of chemical space, and to the prism of current and future biological activities.
Topics: Structure-Activity Relationship; Anti-Bacterial Agents; Antiviral Agents; Antifungal Agents; Melanins
PubMed: 37049953
DOI: 10.3390/molecules28073193 -
Frontiers in Cellular and Infection... 2023The morbidity and mortality of invasive fungal infections are rising gradually. In recent years, fungi have quietly evolved stronger defense capabilities and increased... (Review)
Review
The morbidity and mortality of invasive fungal infections are rising gradually. In recent years, fungi have quietly evolved stronger defense capabilities and increased resistance to antibiotics, posing huge challenges to maintaining physical health. Therefore, developing new drugs and strategies to combat these invasive fungi is crucial. There are a large number of microorganisms in the intestinal tract of mammals, collectively referred to as intestinal microbiota. At the same time, these native microorganisms co-evolve with their hosts in symbiotic relationship. Recent researches have shown that some probiotics and intestinal symbiotic bacteria can inhibit the invasion and colonization of fungi. In this paper, we review the mechanism of some intestinal bacteria affecting the growth and invasion of fungi by targeting the virulence factors, quorum sensing system, secreting active metabolites or regulating the host anti-fungal immune response, so as to provide new strategies for resisting invasive fungal infection.
Topics: Animals; Humans; Mycoses; Fungi; Symbiosis; Intestines; Bacteria; Antifungal Agents; Mammals
PubMed: 37333850
DOI: 10.3389/fcimb.2023.1187831