Marine-Derived Metabolites Act as Promising Antifungal Agents

Marine Drugs, Год журнала: 2024, Номер 22(4), С. 180 - 180

Опубликована: Апрель 17, 2024

The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, echinocandins, face increasing resistance from pathogenic fungi. Therefore, there a pressing need for development novel drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures pharmacological activities. While numerous compounds exhibiting promising activity have been identified, comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we compiled summary derived marine organisms, highlighting diverse action targeting various cellular components, including cell wall, membrane, mitochondria, chromosomes, drug efflux pumps, several biological processes, vesicular trafficking growth hyphae biofilms. This helpful subsequent drugs due its organisms.

Язык: Английский

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Geldanamycin confers fungicidal properties to azole by triggering the activation of succinate dehydrogenase

Life Sciences, Год журнала: 2024, Номер 348, С. 122699 - 122699

Опубликована: Май 6, 2024

Azoles have been widely employed for the treatment of invasive fungal diseases; however, their efficacy is diminished as pathogenic fungi tolerate them due to fungistatic properties. Geldanamycin (GdA) can render azoles fungicidal by inhibiting ATPase and molecular chaperone activities heat shock protein 90 (Hsp90). Nonetheless, clinical applicability GdA restricted its cytotoxic ansamycin scaffold structure, induction cytoprotective responses, conservative nature Hsp90. Hence, it imperative elucidate mechanism action confer properties mitigate toxic adverse effects associated with GdA. Through various experimental methods, including construction gene-deleted Candida albicans mutants, in vitro drug sensitivity experiments, Western blot analysis, reactive oxygen species (ROS) assays, succinate dehydrogenase activity we identified Hsp90 client proteins tolerance C. azoles. It was observed that effectively hindered entry into mitochondria, resulting alleviation inhibitory effect on dehydrogenase. Consequently, activation led an increased production ROS. within thereby facilitating antifungal against albicans. This research presents a novel approach conferring azoles, which involves specifically disrupting interaction between rather than employing non-specific inhibition

Язык: Английский

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Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans

ACS Infectious Diseases, Год журнала: 2024, Номер 10(8), С. 3059 - 3070

Опубликована: Июль 12, 2024

Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs constrained. Emerging evidence indicates that enolase holds promise potential target protein combating IFDs; however, there is currently deficiency in medications specifically targeting enolase. This study establishes isobavachalcone (IBC) exhibits noteworthy efficacy both vitro vivo. Moreover, our has demonstrated IBC effectively targets Eno1

Язык: Английский

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Extracellular fungal Hsp90 represents a promising therapeutic target for combating fungal infections

European Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 207, С. 107041 - 107041

Опубликована: Фев. 12, 2025

Heat shock protein 90 (Hsp90) is a pivotal virulence factor in pathogenic fungi, playing significant role conferring drug resistance. However, due to the high amino acid sequence similarity between fungal and mammalian Hsp90, targeting intracellular Hsp90 therapeutically associated with marked toxic side effects, thereby limiting clinical application. Studies have demonstrated that can be secreted as extracellular (eHsp90), which plays crucial infections. Strategies eHsp90 exhibited promising therapeutic outcomes. Unlike targeting, such antifungal approaches operate without cell penetration, circumventing effects Hsp90's conservation. This review summarizes potential secretion pathways of eHsp90, its roles pathogenesis, well development vaccines antibodies eHsp90. The underlines significance infections suggests represents target for infection treatment.

Язык: Английский

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Biosimilars Targeting Pathogens: A Comprehensive Review of Their Role in Bacterial, Fungal, Parasitic, and Viral Infections

Pharmaceutics, Год журнала: 2025, Номер 17(5), С. 581 - 581

Опубликована: Апрель 28, 2025

Biosimilars represent medicinal products that exhibit a high degree of similarity to an already sanctioned reference biologic agent, with negligible clinically significant disparities concerning safety, purity, or potency. These therapeutic modalities are formulated as economically viable substitutes for established biologics, thereby facilitating increased accessibility sophisticated treatments range medical conditions, including infectious diseases caused by bacterial, fungal, and viral pathogens. The current landscape biosimilars includes proteins, such monoclonal antibodies, antimicrobial peptides, antiviral antifungal peptides. Here, we discuss the obstacles inherent in development biosimilars, rapid mutation rates Furthermore, innovative technologies within domain, antibody engineering, synthetic biology, cell-free protein synthesis, which potential improving potency production efficiency biosimilars. We end prospective outlook highlight importance capacity tackle emerging diseases, highlighting imperative need ongoing research financial commitment.

Язык: Английский

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Diagnostic and clinical management of candida auris infections in immunocompromised patients

Expert Review of Anti-infective Therapy, Год журнала: 2025, Номер unknown

Опубликована: Май 12, 2025

Candida (Candidozyma) auris is an emerging fungal pathogen that poses a significant threat to immunocompromised patients. Its high mortality rates, resistance multiple antifungal classes, and ability spread rapidly in healthcare settings underscore the need for timely accurate diagnosis guide effective clinical management. This special report provides updated overview of C. infections hosts. It discusses current phenotypic molecular diagnostic tools, susceptibility testing methods, infection control strategies. Emerging therapies, including investigational antifungals combination regimens, are also examined light evolving patterns challenges. Despite notable advances diagnostics treatment, major obstacles remain management auris, particularly vulnerable populations. Barriers guideline implementation, lack standardized screening protocols, limited access novel agents continue hinder response. Future efforts should focus on expanding capacity, developing innovative implementing targeted surveillance strategies reduce global burden auris.

Язык: Английский

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Novel Therapeutic Approaches to Control Fungal Biofilms

Springer series on biofilms, Год журнала: 2025, Номер unknown, С. 239 - 279

Опубликована: Янв. 1, 2025

Язык: Английский

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Transcriptomics analysis reveals the effect of Pulsatilla Decoction Butanol Extract on endoplasmic reticulum and peroxisome function of Candida albicans in hyphal state

Journal of Ethnopharmacology, Год журнала: 2024, Номер unknown, С. 118826 - 118826

Опубликована: Сен. 1, 2024

Язык: Английский

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Extracellular Hsp90 of Candida albicans contributes to the virulence of the pathogen by activating the NF-κB signaling pathway and inducing macrophage pyroptosis

Microbiological Research, Год журнала: 2024, Номер 290, С. 127964 - 127964

Опубликована: Ноя. 5, 2024

Язык: Английский

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Diagnostic and Therapeutic Challenge Caused by Candida albicans and Aspergillus spp. Infections in a Pediatric Patient as a Complication of Acute Lymphoblastic Leukemia Treatment: A Case Report and Literature Review

Pathogens, Год журнала: 2024, Номер 13(9), С. 772 - 772

Опубликована: Сен. 7, 2024

Fungal infections constitute a significant challenge and continue to be predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation antifungal prophylaxis, these contribute approximately 20% cases children undergoing for acute lymphoblastic (ALL). The aim this study is highlight diagnostic therapeutic challenges associated with invasive fungal (IFIs). We also present review epidemiology, risk factors, treatment, clinical presentation IFI patients ALL. This case report details course confirmed Candida albicans (C. albicans) Aspergillus spp. during consolidation phase ALL 5-year-old patient. male patient did not experience any complications until Day 28 protocol II. Then, patient’s condition deteriorated. Blood culture detected growth C. albicans. targeted therapy, boy’s show improvement. appearance respiratory symptoms necessitated computed tomography (CT) chest, which revealed multiple nodular densities atypical etiology. In spite ongoing lesions depicted CT scans showed no regression. A lung biopsy ultimately identified species as source infection. Overcoming poses considerable challenge; therefore, an accurate diagnosis prompt initiation therapy are crucial managing leukemia.

Язык: Английский

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