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1.
BMC Plant Biol ; 24(1): 262, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594614

RESUMO

BACKGROUND: Foliar diseases namely late leaf spot (LLS) and leaf rust (LR) reduce yield and deteriorate fodder quality in groundnut. Also the high oleic acid content has emerged as one of the most important traits for industries and consumers due to its increased shelf life and health benefits. RESULTS: Genetic mapping combined with pooled sequencing approaches identified candidate resistance genes (LLSR1 and LLSR2 for LLS and LR1 for LR) for both foliar fungal diseases. The LLS-A02 locus housed LLSR1 gene for LLS resistance, while, LLS-A03 housed LLSR2 and LR1 genes for LLS and LR resistance, respectively. A total of 49 KASPs markers were developed from the genomic regions of important disease resistance genes, such as NBS-LRR, purple acid phosphatase, pentatricopeptide repeat-containing protein, and serine/threonine-protein phosphatase. Among the 49 KASP markers, 41 KASPs were validated successfully on a validation panel of contrasting germplasm and breeding lines. Of the 41 validated KASPs, 39 KASPs were designed for rust and LLS resistance, while two KASPs were developed using fatty acid desaturase (FAD) genes to control high oleic acid levels. These validated KASP markers have been extensively used by various groundnut breeding programs across the world which led to development of thousands of advanced breeding lines and few of them also released for commercial cultivation. CONCLUSION: In this study, high-throughput and cost-effective KASP assays were developed, validated and successfully deployed to improve the resistance against foliar fungal diseases and oleic acid in groundnut. So far deployment of allele-specific and KASP diagnostic markers facilitated development and release of two rust- and LLS-resistant varieties and five high-oleic acid groundnut varieties in India. These validated markers provide opportunities for routine deployment in groundnut breeding programs.


Assuntos
Basidiomycota , Micoses , Resistência à Doença/genética , Ácido Oleico , Melhoramento Vegetal , Mapeamento Cromossômico , Basidiomycota/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
2.
BMC Genomics ; 25(1): 353, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594632

RESUMO

Mosquitoes are prolific vectors of human pathogens, therefore a clear and accurate understanding of the organization of their antimicrobial defenses is crucial for informing the development of transmission control strategies. The canonical infection response in insects, as described in the insect model Drosophila melanogaster, is pathogen type-dependent, with distinct stereotypical responses to Gram-negative bacteria and Gram-positive bacteria/fungi mediated by the activation of the Imd and Toll pathways, respectively. To determine whether this pathogen-specific discrimination is shared by mosquitoes, we used RNAseq to capture the genome-wide transcriptional response of Aedes aegypti and Anopheles gambiae (s.l.) to systemic infection with Gram-negative bacteria, Gram-positive bacteria, yeasts, and filamentous fungi, as well as challenge with heat-killed Gram-negative, Gram-positive, and fungal pathogens. From the resulting data, we found that Ae. aegypti and An. gambiae both mount a core response to all categories of infection, and this response is highly conserved between the two species with respect to both function and orthology. When we compared the transcriptomes of mosquitoes infected with different types of bacteria, we observed that the intensity of the transcriptional response was correlated with both the virulence and growth rate of the infecting pathogen. Exhaustive comparisons of the transcriptomes of Gram-negative-challenged versus Gram-positive-challenged mosquitoes yielded no difference in either species. In Ae. aegypti, however, we identified transcriptional signatures specific to bacterial infection and to fungal infection. The bacterial infection response was dominated by the expression of defensins and cecropins, while the fungal infection response included the disproportionate upregulation of an uncharacterized family of glycine-rich proteins. These signatures were also observed in Ae. aegypti challenged with heat-killed bacteria and fungi, indicating that this species can discriminate between molecular patterns that are specific to bacteria and to fungi.


Assuntos
Aedes , Infecções Bacterianas , Micoses , Animais , Humanos , Drosophila melanogaster , Mosquitos Vetores/genética , Aedes/genética , Aedes/microbiologia , Bactérias , Fungos/genética
3.
Am Nat ; 203(5): 535-550, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38635360

RESUMO

AbstractRecoveries of populations that have suffered severe disease-induced declines are being observed across disparate taxa. Yet we lack theoretical understanding of the drivers and dynamics of recovery in host populations and communities impacted by infectious disease. Motivated by disease-induced declines and nascent recoveries in amphibians, we developed a model to ask the following question: How does the rapid evolution of different host defense strategies affect the transient recovery trajectories of hosts following pathogen invasion and disease-induced declines? We found that while host life history is predictably a major driver of variability in population recovery trajectories (including declines and recoveries), populations that use different host defense strategies (i.e., tolerance, avoidance resistance, and intensity-reduction resistance) experience notably different recoveries. In single-species host populations, populations evolving tolerance recovered on average four times slower than populations evolving resistance. Moreover, while populations using avoidance resistance strategies had the fastest potential recovery rates, these populations could get trapped in long transient states at low abundance prior to recovery. In contrast, the recovery of populations evolving intensity-reduction resistance strategies were more consistent across ecological contexts. Overall, host defense strategies strongly affect the transient dynamics of population recovery and may affect the ultimate fate of real populations recovering from disease-induced declines.


Assuntos
Quitridiomicetos , Micoses , Animais , Anfíbios
4.
J Infect Dev Ctries ; 18(3): 350-354, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38635614

RESUMO

INTRODUCTION: We aimed to investigate the effects of secondary bacterial and fungal infections on patient outcomes in patients followed up in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). METHODOLOGY: We retrospectively analyzed reverse transcriptase polymerase chain reaction (RT-PCR) positive COVID-19 patients followed in the ICU of our hospital between March 2020 and June 2021, using the hospital information system. Demographic data, pathogens causing a secondary infection, onset time of secondary infection, and patient outcomes were recorded. RESULTS: A total of 251 RT-PCR positive patients who met the inclusion criteria were evaluated. The mean length of stay (LOS) in the ICU was 13.3 ± 9.6 days. During this period, 165 (65.7%) patients died. When blood, urine, respiratory tract, and catheter cultures were examined, the number of patients with growth in at least one culture was 129 (51.4%). There was growth in a total of 227 cultures. The highest culture positivity rate was observed in respiratory tract samples (n = 94, 41.4%). Gram-negative bacterial pathogens (n = 130, 58.4%) predominated. Candida spp. was more frequent in urine cultures. The median day of the occurrence of secondary infection was 10 (range: 6-15). Patients who developed secondary infection had a longer LOS and higher mortality rate than patients who did not (p < 0.001). CONCLUSIONS: Gram-negative secondary infections, predominantly in respiratory tract cultures, occurred in COVID-19 patients followed in the ICU. As a result, the LOS was prolonged and mortality rates increased.


Assuntos
COVID-19 , Coinfecção , Micoses , Humanos , Estudos Retrospectivos , Coinfecção/microbiologia , Cuidados Críticos , Micoses/epidemiologia , Unidades de Terapia Intensiva , Bactérias
5.
J Infect Dev Ctries ; 18(3): 473-479, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38635625

RESUMO

INTRODUCTION: Candida albicans and Aspergillus fumigatus are two important agents of Healthcare-associated infections. This study aimed to evaluate the antifungal activity of ozone (O3) gas produced by two commercial devices against cultures of these two species. METHODOLOGY: Sterile plastic plates were inoculated with C. albicans and A. fumigatus and placed on a countertop at three distances (30 cm, 1 m, and 2 m) and three positions in relation to the wall (near, middle, and away), considering the source of O3. Plates were exposed to O3 for one hour and incubated. After incubation, the counting of colony-forming units was performed. As a control, an inoculated plate was incubated, without being exposed to O3. Tests were carried out with two different devices (namely, Mod.I and Mod.II), with the air conditioner on and off, in triplicate. RESULTS: Both devices showed antifungal activity. Mod. I presented better results, due to a higher flow rate. The best activity was on plates at 30 cm, middle position. Contrarily, on plates at 2m, near the wall, the inhibition activity was lower. The best results were obtained with the air conditioner off. Candida albicans was more sensitive to O3 than A. fumigatus. CONCLUSIONS: This method of decontamination by O3 gas shows potential due to its fast and easy execution. The establishment of new protocols for hygiene and hospital disinfection using this approach should be considered, which may reduce environmental contamination by fungi and, consequently, the burden of fungal infections.


Assuntos
Candida albicans , Micoses , Aspergillus fumigatus , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana
8.
Antimicrob Resist Infect Control ; 13(1): 42, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616284

RESUMO

BACKGROUND: COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work. OBJECTIVE: We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection. METHODS: In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability. RESULTS: A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769. CONCLUSIONS: Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.


Assuntos
COVID-19 , Coinfecção , Infecção Hospitalar , Micoses , Adulto , Humanos , Pacientes Internados , Coinfecção/epidemiologia , Interleucina-6 , Estudos Retrospectivos , COVID-19/epidemiologia , Infecção Hospitalar/epidemiologia , Aprendizado de Máquina , Micoses/epidemiologia , Atenção à Saúde
9.
Sci Rep ; 14(1): 8649, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622183

RESUMO

Potentially fatal fungal sphenoid sinusitis (FSS) causes visual damage. However, few studies have reported on its visual impairment and prognosis. Five hundred and eleven FSS patients with ocular complications treated at Beijing Tongren Hospital were recruited and clinical features and visual outcomes were determined. Thirty-two of the 511 patients (6%) had visual impairment, with 13 and 19 patients having invasive and noninvasive FSS, respectively. Eighteen patients (56.25%) had diabetes and 2 patient (6.25%) had long-term systemic use of antibiotics (n = 1) and corticosteroids (n = 1). All patients had visual impairment, which was more severe in invasive FSS than in noninvasive FSS. Bony wall defects and sclerosis were observed in 19 patients (59.38%), and 11 patients (34.38%) had microcalcification in their sphenoid sinusitis on computed tomography (CT). After a 5-year follow-up, three patients (9.38%) died. Patients with noninvasive FSS had a higher improvement rate in visual acuity than their counterparts. In the multivariate analysis, sphenoid sinus wall sclerosis on CT was associated with better visual prognosis. FSS can cause vision loss with persistent headaches, particularly in those with diabetes. CT showed the sphenoid sinus wall sclerosis, indicating a better visual prognosis in FSS with visual impairment.


Assuntos
Diabetes Mellitus , Micoses , Sinusite , Sinusite Esfenoidal , Baixa Visão , Humanos , Sinusite Esfenoidal/complicações , Sinusite Esfenoidal/diagnóstico por imagem , Esclerose , Sinusite/complicações , Sinusite/diagnóstico por imagem , Sinusite/microbiologia , Micoses/complicações , Transtornos da Visão/complicações , Baixa Visão/complicações , Estudos Retrospectivos
10.
J Med Case Rep ; 18(1): 177, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38610059

RESUMO

BACKGROUND: Periprosthetic infection is a serious complication after arthroplasty and is characterized by a long duration, recurrence, and a low cure rate. Although fungal infections are infrequent, they are often catastrophic, with an insidious onset, a long duration, atypical clinical symptoms, and imaging features in the early stage. They are easily misdiagnosed, or the diagnosis is missed, resulting in wrong treatment approaches. CASE PRESENTATION: This paper reports a case involving a 62-year-old female patient of Korean ethnicity with a periprosthetic infection after knee arthroplasty who underwent joint debridement. A preoperative metagenomic next-generation sequencing of joint aspirate revealed Staphylococcus epidermidis. However, postsurgical tissue cultures confirmed the fungal infection. The patient received oral voriconazole and intra-articular injection of voriconazole for antifungal treatment. Since bacterial infection could not be ruled out, we also prescribed levofloxacin. No infection recurrence was observed after more than 22 months of follow-up. In the treatment of this patient, successful short-term follow-up was achieved, but long-term efficacy still cannot be determined. CONCLUSIONS: In addition to the case study, we provide an analysis of the diagnosis and treatment of fungal infection after arthroplasty, especially the efficacy of debridement, antibiotics, and implant retention for a short-term outcome.


Assuntos
Artroplastia do Joelho , Micoses , Feminino , Humanos , Pessoa de Meia-Idade , Artroplastia do Joelho/efeitos adversos , Voriconazol , Desbridamento , Antifúngicos/uso terapêutico
11.
J Cardiothorac Surg ; 19(1): 191, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589959

RESUMO

BACKGROUND: Fungal endocarditis is a rare but serious condition associated with high mortality rates. Various predisposing factors contribute to its occurrence, such as underlying cardiac abnormalities, cardiac surgeries, prosthetic cardiac devices, and central venous catheters. Diagnosing fungal endocarditis, particularly Aspergillus, poses challenges, often complicated by negative blood cultures. CASE PRESENTATION: This report details a case of extensive ascending aorta involvement in Aspergillus endocarditis (AE) in a 24-year-old man with a history of bioprosthesis aortic valve replacement (AVR). Three months post-AVR, he presented with pericardial effusion and aortic rupture, leading to a redo biological valved conduit aortic root replacement (Bentall surgery). Despite the intervention, the tubular graft exhibited extensive Aspergillus involvement, resulting in graft disruption and significant peri-aortic infection. A second redo procedure involving aortic homograft root replacement was performed. Unfortunately, the patient succumbed two days after the surgery. CONCLUSION: A combined approach of medical and surgical therapies is recommended to manage fungal endocarditis. Despite efforts, the mortality rate associated with Aspergillus endocarditis remains unacceptably high, with no significant difference observed between combination therapy and antifungal treatment alone. Further research is essential to explore novel therapeutic strategies and improve outcomes for patients with this challenging condition.


Assuntos
Bioprótese , Endocardite , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Micoses , Humanos , Masculino , Adulto Jovem , Aorta/cirurgia , Aorta Torácica/cirurgia , Valva Aórtica/cirurgia , Bioprótese/efeitos adversos , Endocardite/diagnóstico , Endocardite/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos
12.
Front Cell Infect Microbiol ; 14: 1210857, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590441

RESUMO

Background: Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. Methods: We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Results: Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. Conclusion: mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Micoses , Humanos , Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Sulfonamidas/uso terapêutico
13.
Digit J Ophthalmol ; 30(1): 19-21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601898

RESUMO

Pseudoaneurysm of the internal carotid artery caused by skull base osteomyelitis (SBO) is a lethal condition seen in immunocompromised patients, predominantly those with diabetes mellitus. Cranial nerve involvement is a common complication and generally indicates a poor prognosis. We report the case of a 62-year-old diabetic patient who presented with isolated sixth cranial nerve palsy. She had uncontrolled blood sugar levels and high erythrocyte sedimentation rate, and she suffered from pyelonephritis. Neuroimaging detected SBO with multiple secondary mycotic pseudoaneurysms prominent at the petrocavernous junction. Ischemia is the most common etiology for an isolated abducens nerve palsy, but in certain cases neuroimaging is warranted to prevent life-threatening complications. This case highlights the importance and urgency of identifying and managing such conditions.


Assuntos
Doenças do Nervo Abducente , Falso Aneurisma , Micoses , Osteomielite , Feminino , Humanos , Pessoa de Meia-Idade , Falso Aneurisma/complicações , Falso Aneurisma/diagnóstico , Doenças do Nervo Abducente/etiologia , Doenças do Nervo Abducente/complicações , Base do Crânio , Osteomielite/complicações , Neuroimagem/efeitos adversos , Micoses/complicações
14.
Emerg Infect Dis ; 30(5): 1000-1003, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38666639

RESUMO

We describe the detection of Paranannizziopsis sp. fungus in a wild population of vipers in Europe. Fungal infections were severe, and 1 animal likely died from infection. Surveillance efforts are needed to better understand the threat of this pathogen to snake conservation.


Assuntos
Micoses , Viperidae , Animais , Europa (Continente)/epidemiologia , Micoses/epidemiologia , Micoses/microbiologia , Micoses/veterinária , Animais Selvagens/microbiologia
15.
Int. microbiol ; 27(2): 423-434, Abr. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-232290

RESUMO

Candida spp. is a significant cause of topical and fungal infections in humans. In addition to Candida albicans, many non-albicans species such as C. krusei, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii cause severe infections. The main antifungal agents belong to three different classes, including azoles, polyenes, and echinocandins. However, resistance to all three categories of drugs has been reported. Therefore, there is an urgent need to search for other alternatives with antifungal activity. Many herbal extracts and compounds from natural sources show excellent antifungal activity. In this study, we used an oil extract from the fruits of Zanthoxylum armatum, which showed significant antifungal activity against various Candida spp. by two different methods—minimum inhibitory concentration (MIC) and agar diffusion. In addition, we attempted to explore the possible mechanism of action in C. albicans. It was found that the antifungal activity of Z. armatum oil is fungicidal and involves a decrease in the level of ergosterol in the cell membrane. The decrease in ergosterol level resulted in increased passive diffusion of a fluorescent molecule, rhodamine6G, across the plasma membrane, indicating increased membrane fluidity. The oil-treated cells showed decreased germ tube formation, an important indicator of C. albicans’ virulence. The fungal cells also exhibited decreased attachment to the buccal epithelium, the first step toward invasion, biofilm formation, and damage to oral epithelial cells. Interestingly, unlike most antifungal agents, in which the generation of reactive oxygen species is responsible for killing, no significant effect was observed in the present study. (AU)


Assuntos
Humanos , Candida , Micoses , Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis
16.
Mol Plant Pathol ; 25(3): e13436, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38460112

RESUMO

While the response of Arabidopsis thaliana to drought, herbivory or fungal infection has been well-examined, the consequences of exposure to a series of such (a)biotic stresses are not well studied. This work reports on the genetic mechanisms underlying the Arabidopsis response to single osmotic stress, and to combinatorial stress, either fungal infection using Botrytis cinerea or herbivory using Pieris rapae caterpillars followed by an osmotic stress treatment. Several small-effect genetic loci associated with rosette dry weight (DW), rosette water content (WC), and the projected rosette leaf area in response to combinatorial stress were mapped using univariate and multi-environment genome-wide association approaches. A single-nucleotide polymorphism (SNP) associated with DROUGHT-INDUCED 19 (DI19) was identified by both approaches, supporting its potential involvement in the response to combinatorial stress. Several SNPs were found to be in linkage disequilibrium with known stress-responsive genes such as PEROXIDASE 34 (PRX34), BASIC LEUCINE ZIPPER 25 (bZIP25), RESISTANCE METHYLATED GENE 1 (RMG1) and WHITE RUST RESISTANCE 4 (WRR4). An antagonistic effect between biotic and osmotic stress was found for prx34 and arf4 mutants, which suggests PRX34 and ARF4 play an important role in the response to the combinatorial stress.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Micoses , Estudo de Associação Genômica Ampla , Arabidopsis/microbiologia , Pressão Osmótica , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Proteínas de Arabidopsis/genética
17.
Mycopathologia ; 189(2): 25, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466469

RESUMO

The European Confederation of Medical Mycology (ECMM), formed due to the surge in invasive fungal infections (IFI), initiated the Excellence Centers program in 2016 to guide stakeholders to leading medical mycology sites. This report focuses on the Cologne ECMM Excellence Center, recognized with Diamond status for active global involvement in 2017. The center offers free consultation via email and phone, responding within 24 h for life-threatening IFI, collecting data on origin, pathogens, infection details, and more. Over two years, 189 requests were received globally, predominantly from Germany (85%), mainly involving Aspergillus spp., Mucorales, and Candida spp. Fungal mixed infections occurred in 4% of cases. The center's service effectively addresses IFI challenges, advocating for a comprehensive study encompassing all ECMM Excellence Centers to enhance global mycological care. Proactive expansion of consultancy platforms is crucial, with future analyses needed to assess expert advice's impact on patient outcomes.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Humanos , Micologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Micoses/tratamento farmacológico , Aspergillus , Encaminhamento e Consulta , Antifúngicos/uso terapêutico
18.
World J Microbiol Biotechnol ; 40(4): 129, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459287

RESUMO

Fungal infections represent a challenging threat to the human health. Microsporum gypseum and Trichophyton rubrum are pathogenic fungi causing various topical mycoses in humans. The globally emerging issue of resistance to fungi demands the development of novel therapeutic strategies. In this context, the application of nanoliposomes as vehicles for carrying active therapeutic agents can be a suitable alternative. In this study, rhinacanthin-C was isolated from Rhinacanthus naustus and encapsulated in nano-liposomal formulations, which were prepared by the modified ethanol injection method. The two best formulations composed of soybean phosphatidylcholine (SPC), cholesterol (CHL), and tween 80 (T80) in a molar ratio of 1:1:0 (F1) and 1:1:0.5 (F2) were proceeded for experimentation. The physical characteristics and antifungal activities were performed and compared with solutions of rhinacanthin-C. The rhinacanthin-C encapsulating efficiencies in F1 and F2 were 94.69 ± 1.20% and 84.94 ± 1.32%, respectively. The particle sizes were found to be about 221.4 ± 13.76 nm (F1) and 115.8 ± 23.33 nm (F2), and zeta potential values of -38.16 mV (F1) and -40.98 mV (F2). Similarly, the stability studies of rhinacanthin-C in liposomes demonstrated that rhinacanthin-C in both formulations was more stable in mediums with pH of 4.0 and 6.6 than pure rhinacanthin-C when stored at the same conditions. Rhinacanthin-C in F1 was slightly more stable than F2 when stored in mediums with a pH of 10.0 after three months of storage. However, rhinacanthin-C in both formulations was less stable than pure rhinacanthin-C in a basic medium of pH 10.0. The antifungal potential was evaluated against M. gypsum and T. rubrum. The findings revealed a comparatively higher zone of inhibition for F1. In the MIC study, SPC: CHL: T80 showed higher inhibition against M. gypseum and a slightly higher inhibition against T. rubrum compared to free rhinacanthin-C solution. Moreover, rhinacanthin-C showed significant interaction against 14α-demethylase in in silico study. Overall, this study demonstrates that nanoliposomes containing rhinacanthin-C can improve the stability and antifungal potential of rhinacanthin-C with sustained and prolonged duration of action and could be a promising vehicle for delivery of active ingredients for targeting various fungal infections.


Assuntos
Acanthaceae , Micoses , Naftoquinonas , Humanos , Antifúngicos/farmacologia , Extratos Vegetais/farmacologia , Naftoquinonas/química , Acanthaceae/química
20.
Bioorg Chem ; 145: 107254, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432152

RESUMO

Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.


Assuntos
Antifúngicos , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Ácido Vanílico/farmacologia , Ácido Vanílico/uso terapêutico , Azóis/farmacologia , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Fluconazol/farmacologia , Candida , Candida albicans , Candida glabrata , Inflamação/tratamento farmacológico
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