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Infection and Drug Resistance 2024Fungal infections represent a worldwide concern for public health, due to their prevalence and significant increase in cases each year. Among the most frequent mycoses... (Review)
Review
Fungal infections represent a worldwide concern for public health, due to their prevalence and significant increase in cases each year. Among the most frequent mycoses are those caused by members of the genera , and , which have been treated for years with conventional antifungal drugs, such as flucytosine, azoles, polyenes, and echinocandins. However, these microorganisms have acquired the ability to evade the mechanisms of action of these drugs, thus hindering their treatment. Among the most common evasion mechanisms are alterations in sterol biosynthesis, modifications of drug transport through the cell wall and membrane, alterations of drug targets, phenotypic plasticity, horizontal gene transfer, and chromosomal aneuploidies. Taking into account these problems, some research groups have sought new therapeutic alternatives based on drug repositioning. Through repositioning, it is possible to use existing pharmacological compounds for which their mechanism of action is already established for other diseases, and thus exploit their potential antifungal activity. The advantage offered by these drugs is that they may be less prone to resistance. In this article, a comprehensive review was carried out to highlight the most relevant repositioning drugs to treat fungal infections. These include antibiotics, antivirals, anthelmintics, statins, and anti-inflammatory drugs.
PubMed: 38947372
DOI: 10.2147/IDR.S466336 -
Food Chemistry: X Oct 2024Honey is a natural product used since ancient times due to its taste, aroma, and therapeutic properties (antibacterial, antiviral, anti-inflammatory, and antioxidant... (Review)
Review
Honey is a natural product used since ancient times due to its taste, aroma, and therapeutic properties (antibacterial, antiviral, anti-inflammatory, and antioxidant activity). The purpose of this review is to present the species of microorganisms that can survive in honey and the effect they can have on bees and consumers. The techniques for identifying the microorganisms present in honey are also described in this study. Honey contains bacteria, yeasts, molds, and viruses, and some of them may present beneficial properties for humans. The antimicrobial effect of honey is due to its acidity and high viscosity, high sugar concentration, low water content, the presence of hydrogen peroxide and non-peroxidase components, particularly methylglyoxal (MGO), phenolic acids, flavonoids, proteins, peptides, and non-peroxidase glycopeptides. Honey has antibacterial action (it has effectiveness against bacteria, e.g. , , , and etc.), antifungal (effectiveness against spp., spp. spp. spp. and spp.), antiviral (effectiveness against SARS-CoV-2, Herpes simplex virus type 1, Influenza virus A and B, Varicella zoster virus), and antiparasitic action (effectiveness against and ) demonstrated by numerous studies that are comprised and discussed in this review.
PubMed: 38947342
DOI: 10.1016/j.fochx.2024.101524 -
Food Research International (Ottawa,... Aug 2024Fungal contaminations of cereal grains are a profound food-safety and food-security concern worldwide, threatening consumers' and animals' health and causing enormous...
Fungal contaminations of cereal grains are a profound food-safety and food-security concern worldwide, threatening consumers' and animals' health and causing enormous economic burdens. Because far-ultraviolet C (far-UVC) light at 222 nm has recently been shown to be human-safe, we investigated its efficacy as an alternative to thermal, chemical, and conventional 254 nm UVC anti-fungal treatments. Our microplasma-based far-UVC lamp system achieved a 5.21-log reduction in the conidia of Aspergillus flavus suspended in buffer with a dose of 1032.0 mJ/cm, and a 5.11-log reduction of Fusarium graminearum conidia in suspension with a dose of 619.2 mJ/cm. We further observed that far-UVC treatments could induce fungal-cell apoptosis, alter mitochondrial membrane potential, lead to the accumulation of intracellular reactive oxygen species, cause lipid peroxidation, and result in cell-membrane damage. The lamp system also exhibited a potent ability to inhibit the mycelial growth of both A. flavus and F. graminearum. On potato dextrose agar plates, such growth was completely inhibited after doses of 576.0 mJ/cm and 460.8 mJ/cm, respectively. To test our approach's efficacy at decontaminating actual cereal grains, we designed a cubical 3D treatment chamber fitted with six lamps. At a dose of 780.0 mJ/cm on each side, the chamber achieved a 1.88-log reduction of A. flavus on dried yellow corn kernels and a 1.11-log reduction of F. graminearum on wheat grains, without significant moisture loss to either cereal type (p > 0.05). The treatment did not cause significant changes in the propensity of wheat grains to germinate in the week following treatment (p > 0.05). However, it increased the germination propensity of corn kernels by more than 71% in the same timeframe (p < 0.05). Collectively, our results demonstrate that 222 nm far-UVC radiation can effectively inactivate fungal growth in liquid, on solid surfaces, and on cereal grains. If scalable, its emergence as a safe, cost-effective alternative tool for reducing fungi-related post-harvest cereal losses could have important positive implications for the fight against world hunger and food insecurity.
Topics: Fusarium; Aspergillus flavus; Edible Grain; Ultraviolet Rays; Spores, Fungal; Food Contamination; Food Irradiation; Food Microbiology; Reactive Oxygen Species
PubMed: 38945594
DOI: 10.1016/j.foodres.2024.114550 -
Cureus May 2024Invasive fungal sinusitis (IFS) poses a fatal threat to patients with hematological malignancies or a history of allogeneic hematopoietic stem cell transplant (HSCT)....
Invasive fungal sinusitis (IFS) poses a fatal threat to patients with hematological malignancies or a history of allogeneic hematopoietic stem cell transplant (HSCT). While invasive aspergillosis, a subtype of IFS, remains rare in immunocompetent individuals, allogeneic HSCT recipients face a notable surge in incidence. Despite the rapid onset and progression of IFS, its clinical presentation is subtle, contributing to heightened mortality rates. Prompt surgical debridement and systemic antifungal therapy are required to yield positive results. Examining IFS cases in HSCT recipients is vital, providing insights into its clinical course, prevention strategies, and improved evaluation. We present a rare presentation of IFS with in a relapsed acute myeloid leukemia patient post-HSCT. Two weeks after chemotherapy, the patient developed headaches and blood-tinged sinus drainage in the setting of pancytopenia. Radiologic and pathological findings confirmed the diagnosis of IFS, necessitating weeks of intensive anti-fungal therapy. Despite the initial positive response, the disease ultimately progressed to a fatal outcome. This case emphasizes that early detection is required for a favorable treatment response. Furthermore, it underscores the importance of heightened clinical suspicion, risk stratification, multidisciplinary care, and ongoing research for optimal management of IFS in allogeneic HSCT recipients.
PubMed: 38939236
DOI: 10.7759/cureus.61232 -
Frontiers in Immunology 2024Hematopoietic stem cell transplantation (HSCT) is associated with immune complications and endothelial dysfunction due to intricate donor-recipient interactions,...
INTRODUCTION
Hematopoietic stem cell transplantation (HSCT) is associated with immune complications and endothelial dysfunction due to intricate donor-recipient interactions, conditioning regimens, and inflammatory responses.
METHODS
This study investigated the role of the complement system during HSCT and its interaction with the cytokine network. Seventeen acute myeloid leukemia patients undergoing HSCT were monitored, including blood sampling from the start of the conditioning regimen until four weeks post-transplant. Clinical follow-up was 200 days.
RESULTS
Total complement functional activity was measured by WIELISA and the degree of complement activation by ELISA measurement of sC5b-9. Cytokine release was measured using a 27-multiplex immuno-assay. At all time-points during HSCT complement functional activity remained comparable to healthy controls. Complement activation was continuously stable except for two patients demonstrating increased activation, consistent with severe endotheliopathy and infections. experiments with post-HSCT whole blood challenged with , revealed a hyperinflammatory cytokine response with increased TNF, IL-1β, IL-6 and IL-8 formation. Complement C3 inhibition markedly reduced the cytokine response induced by , , and cholesterol crystals.
DISCUSSION
In conclusion, HSCT patients generally retained a fully functional complement system, whereas activation occurred in patients with severe complications. The complement-cytokine interaction indicates the potential for new complement-targeting therapeutic strategies in HSCT.
Topics: Humans; Male; Hematopoietic Stem Cell Transplantation; Female; Middle Aged; Complement Activation; Adult; Cytokines; Transplantation, Homologous; Aged; Leukemia, Myeloid, Acute; Complement System Proteins; Transplantation Conditioning; Young Adult
PubMed: 38938578
DOI: 10.3389/fimmu.2024.1422370 -
Emerging Infectious Diseases Jun 2024Azole-resistant Aspergillus fumigatus (ARAf) fungi have been found inconsistently in the environment in Denmark since 2010. During 2018-2020, nationwide surveillance of...
Azole-resistant Aspergillus fumigatus (ARAf) fungi have been found inconsistently in the environment in Denmark since 2010. During 2018-2020, nationwide surveillance of clinical A. fumigatus fungi reported environmental TR/L98H or TR/Y121F/T289A resistance mutations in 3.6% of isolates, prompting environmental sampling for ARAf and azole fungicides and investigation of selected ARAf in field and microcosmos experiments. ARAf was ubiquitous (20% of 366 samples; 16% TR/L98H- and 4% TR/Y121F/T289A-related mechanisms), constituting 4.2% of 4,538 A. fumigatus isolates. The highest proportions were in flower- and compost-related samples but were not correlated with azole-fungicide application concentrations. Genotyping showed clustering of tandem repeat-related ARAf and overlaps with clinical isolates in Denmark. A. fumigatus fungi grew poorly in the field experiment with no postapplication change in ARAf proportions. However, in microcosmos experiments, a sustained complete (tebuconazole) or partial (prothioconazole) inhibition against wild-type A. fumigatus but not ARAf indicated that, under some conditions, azole fungicides may favor growth of ARAf in soil.
PubMed: 38935978
DOI: 10.3201/eid3008.240096 -
Medical Mycology Jun 2024Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In...
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.
Topics: Humans; Aspergillus fumigatus; Antifungal Agents; Aspergillosis; World Health Organization; Drug Resistance, Fungal; Voriconazole; Incidence; Microbial Sensitivity Tests; Invasive Fungal Infections; Risk Factors
PubMed: 38935907
DOI: 10.1093/mmy/myad129 -
Indian Journal of Dental Research :... Jan 2024Dental Unit Water Line (DUWL) deliver water to different handpieces in a dental unit. The water in DUWL circulates in a closed system, where it is taken from a...
BACKGROUND
Dental Unit Water Line (DUWL) deliver water to different handpieces in a dental unit. The water in DUWL circulates in a closed system, where it is taken from a container. The quality of dental water is of considerable importance since patients and dental staff are regularly exposed to water and aerosols generated from dental equipment. Output water from DUWLs may be a potential source of infection for both dental health care personnel and patients.
AIM
To assess the microbial contamination in the DUWL among dental clinics in Chennai.
MATERIALS AND METHODS
An in vitro study was conducted on 60 water samples from 20 dental clinics in Chennai in December 2019. Water samples were collected from three different sources of the Dental unit according to ADA guidelines. The collected samples were assessed for the presence of Aspergillus, Acinetobacter, Pseudomonas aeruginosa, and Legionella by agar plate method. The data were analysed using SPSS software version 20.
RESULTS
Legionella was the most prevalent microorganism with 70% prevalence in a three-way syringe and 50% in scaler and airotor, followed by Pseudomonas aeruginosa and Acinetobacter with 10% prevalence in scaler and airotor and Aspergillus with a prevalence of 10% in the three-way syringe.
CONCLUSION
Most of the dental units were contaminated with Aspergillus, Legionella, Pseudomonas aeruginosa and Acinetobacter which pose a serious threat to the patients as well as the dentists.
Topics: India; Dental Clinics; Equipment Contamination; Water Microbiology; Dental Equipment; Humans; Legionella; Pseudomonas aeruginosa; Acinetobacter; In Vitro Techniques
PubMed: 38934755
DOI: 10.4103/ijdr.ijdr_463_22 -
Journal of Food and Drug Analysis Jun 2024Aflatoxin B, a major global food safety concern, is produced by toxigenic fungi during crop growing, drying, and storage, and shows increasing annual prevalence. This...
Aflatoxin B, a major global food safety concern, is produced by toxigenic fungi during crop growing, drying, and storage, and shows increasing annual prevalence. This study aimed to detect aflatoxin B in chili samples using ATR-FTIR coupled with machine learning algorithms. We found that 83.6% of the chili powder samples were contaminated with Aspergillus and Penicillium species, with aflatoxin B levels ranging from 7.63 to 44.32 μg/kg. ATR-FTIR spectroscopy in the fingerprint region (1800-400 cm) showed peak intensity variation in the bands at 1587, 1393, and 1038 cm, which are mostly related to aflatoxin B structure. The PCA plots from samples with different trace amounts of aflatoxin B could not be separated. Vibrational spectroscopy combined with machine learning was applied to address this issue. The logistic regression model had the best F1 score with the highest %accuracy (73%), %sensitivity (73%), and %specificity (71%), followed by random forest and support vector machine models. Although the logistic regression model contributed significant findings, this study represents a laboratory research project. Because of the peculiarities of the ATR-FTIR spectral measurements, the spectra measured for several batches may differ, necessitating running the model on multiple spectral ranges and using increased sample sizes in subsequent applications. This proposed method has the potential to provide rapid and accurate results and may be valuable in future applications regarding toxin detection in foods when simple onsite testing is required.
Topics: Capsicum; Spectroscopy, Fourier Transform Infrared; Aflatoxin B1; Food Contamination; Aspergillus; Powders; Penicillium
PubMed: 38934688
DOI: 10.38212/2224-6614.3497 -
MBio Jun 2024Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an...
Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an urgent need to develop novel antifungal compounds that are effective against drug-resistant filamentous fungi. Here, we utilized an cell-based high-throughput screen to identify small molecules with antifungal activity that also potentiated triazole activity. The screen identified 16 hits with promising activity against . A nonspirocyclic piperidine, herein named MBX-7591, exhibited synergy with triazole antifungal drugs and activity against pan-azole-resistant isolates. MBX-7591 has additional potent activity against species and CO-dependent activity against . Chemical, genetic, and biochemical mode of action analyses revealed that MBX-7591 increases cell membrane saturation by decreasing oleic acid content. MBX-7591 has low toxicity and shows good efficacy in decreasing fungal burden in a murine model of invasive pulmonary aspergillosis. Taken together, our results suggest MBX-7591 is a promising hit with a novel mode of action for further antifungal drug development to combat the rising incidence of triazole-resistant filamentous fungal infections.IMPORTANCEThe incidence of infections caused by fungi continues to increase with advances in medical therapies. Unfortunately, antifungal drug development has not kept pace with the incidence and importance of fungal infections, with only three major classes of antifungal drugs currently available for use in the clinic. Filamentous fungi, also called molds, are particularly recalcitrant to contemporary antifungal therapies. Here, a recently developed cell reporter strain was utilized to conduct a high-throughput screen to identify small molecules with antifungal activity. An emphasis was placed on small molecules that potentiated the activity of contemporary triazole antifungals and led to the discovery of MBX-7591. MBX-7591 potentiates triazole activity against drug-resistant molds such as and has activity against Mucorales fungi. MBX-7591's mode of action involves inhibiting the conversion of saturated to unsaturated fatty acids, thereby impacting fungal membrane integrity. MBX-7591 is a novel small molecule with antifungal activity poised for lead development.
PubMed: 38934618
DOI: 10.1128/mbio.01166-24