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The Exocyst Subunits EqSec5 and EqSec6 Promote Powdery Mildew Fungus Growth and Pathogenicity.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-17 DOI: 10.3390/jof11010073
Jinyao Yin, Xuehuan Zhu, Yalong Chen, Yanyang Lv, Jiaxin Shan, Yuhan Liu, Wenbo Liu, Weiguo Miao, Xiao Li

The exocyst complex in eukaryotic cells modulates secretory vesicle transportation to promote exocytosis. The exocyst is also required for the hyphal growth and pathogenic development of several filamentous phytopathogens. Obligate biotrophic powdery mildew fungi cause considerable damage to many cash crops; however, the exocyst's roles in this group of fungi is not well studied. To verify the functions of the exocyst in powdery mildew fungus, we identified two exocyst subunits, EqSec5 and EqSec6, from Erysiphe quercicola, a powdery mildew fungus that infects the rubber tree Hevea brasiliensis. When GFP-fused EqSec5 and EqSec6 were introduced into E. quercicola and another phytopathogenic fungus, Magnaporthe oryzae, they primarily localized to the hyphal tip region. Inducing gene silencing of EqSec5 or EqSec6 caused growth and infection defects, and those defects could not be fully restored under the NADPH oxidase inhibitor treatment to the plant. The silenced strains also induced the host defense response including reactive oxygen species accumulation and callose deposition. The silencing of EqSec5 or EqSec6 also inhibited the secretion of the effector protein EqIsc1, interrupting plant salicylic acid biosynthesis. Yeast two-hybrid and gene overexpression assays suggested that EqSec5 and EqSec6 interact with each other and can complement each other's function during host infection. Overall, our study provides evidence that the exocyst in this powdery mildew fungus facilitates effector secretion, hyphal growth, and infection.

{"title":"The Exocyst Subunits EqSec5 and EqSec6 Promote Powdery Mildew Fungus Growth and Pathogenicity.","authors":"Jinyao Yin, Xuehuan Zhu, Yalong Chen, Yanyang Lv, Jiaxin Shan, Yuhan Liu, Wenbo Liu, Weiguo Miao, Xiao Li","doi":"10.3390/jof11010073","DOIUrl":"10.3390/jof11010073","url":null,"abstract":"<p><p>The exocyst complex in eukaryotic cells modulates secretory vesicle transportation to promote exocytosis. The exocyst is also required for the hyphal growth and pathogenic development of several filamentous phytopathogens. Obligate biotrophic powdery mildew fungi cause considerable damage to many cash crops; however, the exocyst's roles in this group of fungi is not well studied. To verify the functions of the exocyst in powdery mildew fungus, we identified two exocyst subunits, EqSec5 and EqSec6, from <i>Erysiphe quercicola</i>, a powdery mildew fungus that infects the rubber tree <i>Hevea brasiliensis</i>. When GFP-fused EqSec5 and EqSec6 were introduced into <i>E. quercicola</i> and another phytopathogenic fungus, <i>Magnaporthe oryzae</i>, they primarily localized to the hyphal tip region. Inducing gene silencing of <i>EqSec5</i> or <i>EqSec6</i> caused growth and infection defects, and those defects could not be fully restored under the NADPH oxidase inhibitor treatment to the plant. The silenced strains also induced the host defense response including reactive oxygen species accumulation and callose deposition. The silencing of <i>EqSec5</i> or <i>EqSec6</i> also inhibited the secretion of the effector protein EqIsc1, interrupting plant salicylic acid biosynthesis. Yeast two-hybrid and gene overexpression assays suggested that EqSec5 and EqSec6 interact with each other and can complement each other's function during host infection. Overall, our study provides evidence that the exocyst in this powdery mildew fungus facilitates effector secretion, hyphal growth, and infection.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Invasive Aspergillosis in the Intensive Care Unit.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-17 DOI: 10.3390/jof11010070
Anna Zubovskaia, Jose A Vazquez

Invasive aspergillosis (IA) is a fungal infection, which has traditionally been associated with neutropenia and immunosuppressive therapies. Our understanding of invasive aspergillosis has been evolving and, in the past few decades, IA among ICU patients has been recognized as a common infection and has become more widely recognized. The diagnosis and management of invasive aspergillosis in the ICU is particularly challenging, due to the unstable clinical condition of the patients, lack of diagnostic markers, increased risk of further clinical deterioration, multiple comorbidities, and a need for early assessment and treatment. In this article, we will discuss the challenges and pitfalls of the diagnosis and management of invasive aspergillosis in an ICU setting, along with a review of the current literature that is pertinent and specific to this population.

{"title":"Invasive Aspergillosis in the Intensive Care Unit.","authors":"Anna Zubovskaia, Jose A Vazquez","doi":"10.3390/jof11010070","DOIUrl":"10.3390/jof11010070","url":null,"abstract":"<p><p>Invasive aspergillosis (IA) is a fungal infection, which has traditionally been associated with neutropenia and immunosuppressive therapies. Our understanding of invasive aspergillosis has been evolving and, in the past few decades, IA among ICU patients has been recognized as a common infection and has become more widely recognized. The diagnosis and management of invasive aspergillosis in the ICU is particularly challenging, due to the unstable clinical condition of the patients, lack of diagnostic markers, increased risk of further clinical deterioration, multiple comorbidities, and a need for early assessment and treatment. In this article, we will discuss the challenges and pitfalls of the diagnosis and management of invasive aspergillosis in an ICU setting, along with a review of the current literature that is pertinent and specific to this population.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deletion of bZIP Transcription Factor PratfA Reveals Specialized Metabolites Potentially Regulating Stress Response in Penicillium raistrickii.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-17 DOI: 10.3390/jof11010072
Anxin Zhang, Shu Zhang, Xinran Xu, Wen-Bing Yin

Fungal secondary metabolism (SM) is highly correlated with physiological processes that are typically regulated by pleiotropic regulators. In this study, we purposefully altered PratfA, a crucial regulator associated with oxidative stress in Penicillium raistrickii CGMCC 3.1066. After the knockout of PratfA, a novel polyketide (PK) raistrilide A (1) and the known nonribosomal peptide (NRP) tunicoidine (2) subsequently disappeared. Notably, compound 1 is a rare octaketone derivative and contains two unsubstituted cis-double bonds, demonstrating its unique biosynthetic mechanism. The knockout of PratfA resulted in the disappearance of 1-2 and greatly increased the susceptibility of ΔPratfA mutant strain to oxidative stress, rendering it nearly impossible to survive in such environments. At present, the OE⸬PratfA strain showed no phenotypic or oxidative stress sensitivity differences compared to the wild-type strain. Our findings highlight that the oxidative-stress-related transcription factor (TF) PratfA influences SM pathways in P. raistrickii. The manipulation of regulatory factors can guide the discovery of novel natural products (NPs).

{"title":"Deletion of bZIP Transcription Factor <i>PratfA</i> Reveals Specialized Metabolites Potentially Regulating Stress Response in <i>Penicillium raistrickii</i>.","authors":"Anxin Zhang, Shu Zhang, Xinran Xu, Wen-Bing Yin","doi":"10.3390/jof11010072","DOIUrl":"10.3390/jof11010072","url":null,"abstract":"<p><p>Fungal secondary metabolism (SM) is highly correlated with physiological processes that are typically regulated by pleiotropic regulators. In this study, we purposefully altered <i>PratfA</i>, a crucial regulator associated with oxidative stress in <i>Penicillium raistrickii</i> CGMCC 3.1066. After the knockout of <i>PratfA</i>, a novel polyketide (PK) raistrilide A (<b>1</b>) and the known nonribosomal peptide (NRP) tunicoidine (<b>2</b>) subsequently disappeared. Notably, compound <b>1</b> is a rare octaketone derivative and contains two unsubstituted <i>cis</i>-double bonds, demonstrating its unique biosynthetic mechanism. The knockout of <i>PratfA</i> resulted in the disappearance of <b>1</b>-<b>2</b> and greatly increased the susceptibility of Δ<i>PratfA</i> mutant strain to oxidative stress, rendering it nearly impossible to survive in such environments. At present, the <i>OE⸬PratfA</i> strain showed no phenotypic or oxidative stress sensitivity differences compared to the wild-type strain. Our findings highlight that the oxidative-stress-related transcription factor (TF) <i>PratfA</i> influences SM pathways in <i>P</i>. <i>raistrickii</i>. The manipulation of regulatory factors can guide the discovery of novel natural products (NPs).</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mycological Profile and Associated Factors Among Patients with Dermatophytosis in Astana, Kazakhstan.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-16 DOI: 10.3390/jof11010065
Alma Aimoldina, Ainura Smagulova, Gulnar Batpenova, Nellie Konnikov, Togzhan Algazina, Zulfiya Jetpisbayeva, Dinara Azanbayeva, Darkhan Amantayev, Vladimir Kiyan

Dermatophytosis, also known as Tinea infection, remains a significant interdisciplinary concern worldwide. This dermatophyte infection may be more serious in individuals with underlying somatic diseases, immunodeficiencies, endocrine disorders, or chronic illnesses. This study analyzed 313 patients with suspected dermatophytosis. Data were gathered through questionnaires and medical records were reviewed. Biological samples were cultured on Sabouraud dextrose agar, and PCR was employed to assess the genetic diversity of strains. Statistical analysis was conducted using SPSS version 26. The overall prevalence of dermatophytosis in the cohort was 30.4%. Among the cultured isolates, 73.7% were identified as Microsporum canis, while 26.3% were identified as Trichophyton species, including T. mentagrophytes, T. tonsurans, and T. verrucosum. Several factors were significantly associated with an increased risk of dermatophytosis, including the following: male gender (AOR = 1.97), age 1-10 years (AOR = 3.80), living in rural areas (AOR = 2.30), visiting public bathhouses (AOR = 2.32), visiting massage parlors (AOR = 1.39), contact with cats (AOR = 2.32), family history of dermatophytosis (AOR = 3.04), and sexual contact with an infected or unknown partner (AOR = 3.08). Dermatophytosis was identified in approximately one third of the patients by culture (30.4%), with the risk heightened in individuals under 10 years old (43.6%), those living in rural areas (33.3%), and those with a family history of dermatophytosis (35.7%) or close contact with cats (39.4%). The findings underscore the need for strengthened preventive measures and targeted diagnostics, particularly among high-risk groups.

{"title":"Mycological Profile and Associated Factors Among Patients with Dermatophytosis in Astana, Kazakhstan.","authors":"Alma Aimoldina, Ainura Smagulova, Gulnar Batpenova, Nellie Konnikov, Togzhan Algazina, Zulfiya Jetpisbayeva, Dinara Azanbayeva, Darkhan Amantayev, Vladimir Kiyan","doi":"10.3390/jof11010065","DOIUrl":"10.3390/jof11010065","url":null,"abstract":"<p><p>Dermatophytosis, also known as Tinea infection, remains a significant interdisciplinary concern worldwide. This dermatophyte infection may be more serious in individuals with underlying somatic diseases, immunodeficiencies, endocrine disorders, or chronic illnesses. This study analyzed 313 patients with suspected dermatophytosis. Data were gathered through questionnaires and medical records were reviewed. Biological samples were cultured on Sabouraud dextrose agar, and PCR was employed to assess the genetic diversity of strains. Statistical analysis was conducted using SPSS version 26. The overall prevalence of dermatophytosis in the cohort was 30.4%. Among the cultured isolates, 73.7% were identified as <i>Microsporum canis</i>, while 26.3% were identified as <i>Trichophyton</i> species, including <i>T. mentagrophytes</i>, <i>T. tonsurans</i>, and <i>T. verrucosum</i>. Several factors were significantly associated with an increased risk of dermatophytosis, including the following: male gender (AOR = 1.97), age 1-10 years (AOR = 3.80), living in rural areas (AOR = 2.30), visiting public bathhouses (AOR = 2.32), visiting massage parlors (AOR = 1.39), contact with cats (AOR = 2.32), family history of dermatophytosis (AOR = 3.04), and sexual contact with an infected or unknown partner (AOR = 3.08). Dermatophytosis was identified in approximately one third of the patients by culture (30.4%), with the risk heightened in individuals under 10 years old (43.6%), those living in rural areas (33.3%), and those with a family history of dermatophytosis (35.7%) or close contact with cats (39.4%). The findings underscore the need for strengthened preventive measures and targeted diagnostics, particularly among high-risk groups.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimizing Bioaugmentation for Pharmaceutical Stabilization of Sewage Sludge: A Study on Short-Term Composting Under Real Conditions.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-16 DOI: 10.3390/jof11010067
Gabriela Angeles-De Paz, Juan Cubero-Cardoso, Clementina Pozo, Concepción Calvo, Elisabet Aranda, Tatiana Robledo-Mahón

A significant concentration of pharmaceuticals has been detected within composted sewage sludge. Their uncomplete removal and lack of monitoring during composting neglects their potentially toxic effects when used as a soil organic amendment. Previously, we successfully implemented a bioaugmentation-composting system focused on toxicity and pharmaceuticals' concentration reduction. This method, however, comprised a long inoculant-acclimatization period, making it an unprofitable technology. Hence, this work aimed to explore a shorter and yet effective composting process by simultaneously implementing the inoculation of a native microbial consortium and the fungus Penicillium oxalicum XD 3.1 in composting piles of sewage sludge and olive prunings. All the piles were subjected to frequent inoculation, windrow turning, and monitoring of the physicochemical and biological parameters. Additionally, both the bioaugmentation stability and pharmaceuticals degradation were evaluated through different analysis and removal rates calculations. One hundred days earlier than previous attempts, both bioaugmentation treatments achieved adequate composting conditions, maintained core native populations while improving the degrading microbial diversity, and achieved around 70-72% of pharmaceutical remotion. Nevertheless, only Penicillium inoculation produced favorable toxicity results ideal for organic amendments (acute microtoxicity and phytotoxicity). Thus, a shorter but equally stable and effective degrading bioaugmentation-composting with P. oxalicum was achieved here.

{"title":"Optimizing Bioaugmentation for Pharmaceutical Stabilization of Sewage Sludge: A Study on Short-Term Composting Under Real Conditions.","authors":"Gabriela Angeles-De Paz, Juan Cubero-Cardoso, Clementina Pozo, Concepción Calvo, Elisabet Aranda, Tatiana Robledo-Mahón","doi":"10.3390/jof11010067","DOIUrl":"10.3390/jof11010067","url":null,"abstract":"<p><p>A significant concentration of pharmaceuticals has been detected within composted sewage sludge. Their uncomplete removal and lack of monitoring during composting neglects their potentially toxic effects when used as a soil organic amendment. Previously, we successfully implemented a bioaugmentation-composting system focused on toxicity and pharmaceuticals' concentration reduction. This method, however, comprised a long inoculant-acclimatization period, making it an unprofitable technology. Hence, this work aimed to explore a shorter and yet effective composting process by simultaneously implementing the inoculation of a native microbial consortium and the fungus <i>Penicillium oxalicum</i> XD 3.1 in composting piles of sewage sludge and olive prunings. All the piles were subjected to frequent inoculation, windrow turning, and monitoring of the physicochemical and biological parameters. Additionally, both the bioaugmentation stability and pharmaceuticals degradation were evaluated through different analysis and removal rates calculations. One hundred days earlier than previous attempts, both bioaugmentation treatments achieved adequate composting conditions, maintained core native populations while improving the degrading microbial diversity, and achieved around 70-72% of pharmaceutical remotion. Nevertheless, only <i>Penicillium</i> inoculation produced favorable toxicity results ideal for organic amendments (acute microtoxicity and phytotoxicity). Thus, a shorter but equally stable and effective degrading bioaugmentation-composting with <i>P. oxalicum</i> was achieved here.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gene Expression in Aphelid Zoospores Reveals Their Transcriptional and Translational Activity and Alacrity for Invasion.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-16 DOI: 10.3390/jof11010068
Igor R Pozdnyakov, Alexei O Seliuk, Kristina O Barzasekova, Sergey A Karpov

In Aphelidium insulamus (Opisthokonta, Aphelida) zoospores, the expression of 7708 genes out of 7802 described genes was detected. For 589 of them, expression levels were shown to be more than 10 times higher than the median level. Among the highly expressed genes with known functions, the largest functional categories were "Cellular Metabolism", "Protein Synthesis", "Cell State Control", and "Nucleic Acid Processing". Unlike fungal zoospores, translational and transcriptional activity was demonstrated for A. insulamus zoospores. With increasing temperature, the expression of many zoospore genes changed dramatically; the expression of heat shock and chaperone protein genes multiplied more than 30 times, indicating the high sensitivity of aphelid zoospores and their response to environmental changes.

{"title":"Gene Expression in Aphelid Zoospores Reveals Their Transcriptional and Translational Activity and Alacrity for Invasion.","authors":"Igor R Pozdnyakov, Alexei O Seliuk, Kristina O Barzasekova, Sergey A Karpov","doi":"10.3390/jof11010068","DOIUrl":"10.3390/jof11010068","url":null,"abstract":"<p><p>In <i>Aphelidium insulamus</i> (Opisthokonta, Aphelida) zoospores, the expression of 7708 genes out of 7802 described genes was detected. For 589 of them, expression levels were shown to be more than 10 times higher than the median level. Among the highly expressed genes with known functions, the largest functional categories were \"Cellular Metabolism\", \"Protein Synthesis\", \"Cell State Control\", and \"Nucleic Acid Processing\". Unlike fungal zoospores, translational and transcriptional activity was demonstrated for <i>A. insulamus</i> zoospores. With increasing temperature, the expression of many zoospore genes changed dramatically; the expression of heat shock and chaperone protein genes multiplied more than 30 times, indicating the high sensitivity of aphelid zoospores and their response to environmental changes.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human Fungal Infections: Diagnostic and Therapeutic Challenges.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-16 DOI: 10.3390/jof11010066
Timoleon-Achilleas Vyzantiadis, Eleni Gavriilaki, Athanasios Tragiannidis

Fungal infections, either invasive and disseminated or cutaneous and superficial, are an important and increasing cause of morbidity [...].

{"title":"Human Fungal Infections: Diagnostic and Therapeutic Challenges.","authors":"Timoleon-Achilleas Vyzantiadis, Eleni Gavriilaki, Athanasios Tragiannidis","doi":"10.3390/jof11010066","DOIUrl":"10.3390/jof11010066","url":null,"abstract":"<p><p>Fungal infections, either invasive and disseminated or cutaneous and superficial, are an important and increasing cause of morbidity [...].</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel 2-Thiazolylhydrazone with Druggable Properties for Antifungal Application.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-16 DOI: 10.3390/jof11010069
Wallace Cordeiro de Morais, Gustavo Henrique Oliveira Costa, Vinícius Leal Pitcella, João Victor Vanolli Protti, Carolina Paula de Souza Moreira, José Eduardo Gonçalves, Susana Johann, Renata Barbosa de Oliveira

Fungal infections have become a growing concern in healthcare, particularly in immunocompromised individuals, with species like Candida, Cryptococcus, and Sporothrix posing significant challenges due to rising resistance and limited treatment options. In response, novel antifungal agents are being explored, including thiazolyl hydrazones. This study focuses on the development of a novel thiazolylhydrazone derivative, RW3. RW3 was synthesized to improve its water solubility and pharmacokinetic properties. The compound demonstrated a broad antifungal spectrum, particularly effective against Cryptococcus neoformans and Candida auris, with minimal irritant potential and low cytotoxicity. RW3 showed favorable solubility and high intestinal permeability, indicating potential for oral administration. The results suggest RW3 as a promising lead for further development as a therapeutic agent for systemic fungal infections. These findings underscore the importance of optimizing drug properties to enhance efficacy and safety profiles, opening the path for the development of innovative antifungal treatments.

{"title":"Novel 2-Thiazolylhydrazone with Druggable Properties for Antifungal Application.","authors":"Wallace Cordeiro de Morais, Gustavo Henrique Oliveira Costa, Vinícius Leal Pitcella, João Victor Vanolli Protti, Carolina Paula de Souza Moreira, José Eduardo Gonçalves, Susana Johann, Renata Barbosa de Oliveira","doi":"10.3390/jof11010069","DOIUrl":"10.3390/jof11010069","url":null,"abstract":"<p><p>Fungal infections have become a growing concern in healthcare, particularly in immunocompromised individuals, with species like <i>Candida</i>, <i>Cryptococcus</i>, and <i>Sporothrix</i> posing significant challenges due to rising resistance and limited treatment options. In response, novel antifungal agents are being explored, including thiazolyl hydrazones. This study focuses on the development of a novel thiazolylhydrazone derivative, RW3. RW3 was synthesized to improve its water solubility and pharmacokinetic properties. The compound demonstrated a broad antifungal spectrum, particularly effective against <i>Cryptococcus neoformans</i> and <i>Candida auris</i>, with minimal irritant potential and low cytotoxicity. RW3 showed favorable solubility and high intestinal permeability, indicating potential for oral administration. The results suggest RW3 as a promising lead for further development as a therapeutic agent for systemic fungal infections. These findings underscore the importance of optimizing drug properties to enhance efficacy and safety profiles, opening the path for the development of innovative antifungal treatments.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptomic Analysis Reveals Molecular Mechanisms Underpinning Mycovirus-Mediated Hypervirulence in Beauveria bassiana Infecting Tenebrio molitor.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-15 DOI: 10.3390/jof11010063
Charalampos Filippou, Robert H A Coutts, Ioly Kotta-Loizou, Sam El-Kamand, Alexie Papanicolaou

Mycoviral infection can either be asymptomatic or have marked effects on fungal hosts, influencing them either positively or negatively. To fully understand the effects of mycovirus infection on the fungal host, transcriptomic profiling of four Beauveria bassiana isolates, including EABb 92/11-Dm that harbors mycoviruses, was performed 48 h following infection of Tenebrio molitor via topical application or injection. Genes that participate in carbohydrate assimilation and transportation, and those essential for fungal survival and oxidative stress tolerance, calcium uptake, and iron uptake, were found to be overexpressed in the virus-infected isolate during the mid-infection stage. Mycotoxin genes encoding bassianolide and oosporein were switched off in all isolates. However, beauvericin, a mycotoxin capable of inducing oxidative stress at the molecular level, was expressed in all four isolates, indicating an important contribution to virulence against T. molitor. These observations suggest that detoxification of immune-related (oxidative) defenses and nutrient scouting, as mediated by these genes, occurs in mid-infection during the internal growth phase. Consequently, we observe a symbiotic relationship between mycovirus and fungus that does not afflict the host; on the contrary, it enhances the expression of key genes leading to a mycovirus-mediated hypervirulence effect.

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引用次数: 0
Correlation Between Cryptococcus Infection and the Nasal Mycobiota in a Population of Free-Ranging Koalas (Phascolarctos cinereus) in New South Wales, Australia.
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2025-01-15 DOI: 10.3390/jof11010064
Andrew S McPherson, Sophie L Haworth, Alex Kan, Luisa Monteiro de Miranda, Mark B Krockenberger

Cryptococcosis is a fungal disease in humans and animals, caused by the Cryptococcus neoformans and Cryptococcus gattii species complexes. Clinical cryptococcosis primarily manifests as upper respiratory tract disease; however, dissemination to other organs, particularly the brain, can occur. Nasal colonisation and subclinical cryptococcosis are common in koalas (Phascolarctos cinereus) due to their shared environmental niche with Cryptococcus: Eucalyptus trees. However, for reasons that remain unclear, the prevalence of clinical disease is low in koalas. Interactions between respiratory pathogens and the nasal mycobiome are thought to play a role in the development and progression of numerous respiratory diseases. As such, this study aimed to characterise the mycobiome of the nasal vestibule in koalas with and without evidence of cryptococcal colonisation and subclinical disease via the next-generation sequencing (NGS) of the ITS1 region of the fungal internal transcribed spacer (ITS) gene. Samples were collected from 47 koalas from a population of free-ranging koalas in the Liverpool Plains, NSW, Australia, with a known history of Cryptococcus exposure and nasal colonisation. Of the 47 animals tested, 6.4% were culture-positive only, 4.3% were seropositive only, and 2.1% were culture- and seropositive. C. gattii was detected in four samples via NGS. C. neoformans was not detected via NGS. There were no significant differences in the nasal mycobiomes of Cryptococcus-positive and -negative animals; thus, we could not establish a definitive association between the mycobiome and infection outcomes. We identified a number of fungal genera that were significantly more abundant in samples from Cryptococcus-positive animals, but there was no apparent relationship between these genera and the development of cryptococcosis. This study represents the first investigation of the nasal mycobiota of wild koalas. Further studies involving koalas with clinical disease are necessary to determine the role of the nasal mycobiota in the development of cryptococcosis.

{"title":"Correlation Between <i>Cryptococcus</i> Infection and the Nasal Mycobiota in a Population of Free-Ranging Koalas (<i>Phascolarctos cinereus</i>) in New South Wales, Australia.","authors":"Andrew S McPherson, Sophie L Haworth, Alex Kan, Luisa Monteiro de Miranda, Mark B Krockenberger","doi":"10.3390/jof11010064","DOIUrl":"10.3390/jof11010064","url":null,"abstract":"<p><p>Cryptococcosis is a fungal disease in humans and animals, caused by the <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complexes. Clinical cryptococcosis primarily manifests as upper respiratory tract disease; however, dissemination to other organs, particularly the brain, can occur. Nasal colonisation and subclinical cryptococcosis are common in koalas (<i>Phascolarctos cinereus</i>) due to their shared environmental niche with <i>Cryptococcus</i>: <i>Eucalyptus</i> trees. However, for reasons that remain unclear, the prevalence of clinical disease is low in koalas. Interactions between respiratory pathogens and the nasal mycobiome are thought to play a role in the development and progression of numerous respiratory diseases. As such, this study aimed to characterise the mycobiome of the nasal vestibule in koalas with and without evidence of cryptococcal colonisation and subclinical disease via the next-generation sequencing (NGS) of the ITS1 region of the fungal internal transcribed spacer (ITS) gene. Samples were collected from 47 koalas from a population of free-ranging koalas in the Liverpool Plains, NSW, Australia, with a known history of <i>Cryptococcus</i> exposure and nasal colonisation. Of the 47 animals tested, 6.4% were culture-positive only, 4.3% were seropositive only, and 2.1% were culture- and seropositive. <i>C. gattii</i> was detected in four samples via NGS. <i>C. neoformans</i> was not detected via NGS. There were no significant differences in the nasal mycobiomes of <i>Cryptococcus</i>-positive and -negative animals; thus, we could not establish a definitive association between the mycobiome and infection outcomes. We identified a number of fungal genera that were significantly more abundant in samples from <i>Cryptococcus</i>-positive animals, but there was no apparent relationship between these genera and the development of cryptococcosis. This study represents the first investigation of the nasal mycobiota of wild koalas. Further studies involving koalas with clinical disease are necessary to determine the role of the nasal mycobiota in the development of cryptococcosis.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Fungi
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