Efficacy of two novel antifungal lipopeptides, AF4 and AF5 of bacillomycin D family in murine models of invasive candidiasis, cryptococcosis, and aspergillosis DOI Creative Commons
Raees A. Paul,

Madhuri Madduri,

Nisha Kashyap

и другие.

Apmis, Год журнала: 2024, Номер 133(1)

Опубликована: Дек. 25, 2024

Invasive fungal diseases are an important public health concern due to increase in the at‐risk population and high mortality associated with these infections. Managing invasive infections poses a significant challenge given limited antifungal options emergence of resistance key pathogens. Through comprehensive approach, we evaluated vitro activity vivo efficacy two novel lipopeptides, AF 4 5 murine models disseminated candidiasis, cryptococcosis, aspergillosis. Flow cytometry analysis propidium iodide showed dose‐dependent permeability disruption cell membranes, underscoring membrane perturbing effects . These observations were further substantiated by SEM analyses that yeast hyphal deformation leakage cellular contents. Our investigations utilizing doses (5 10 mg/kg bodyweight) each lipopeptide its comparison standard therapies lipopeptides significantly improved odds mice survival candidiasis cryptococcosis models, reduction organ burden 2 3‐log order. Additionally, aspergillosis model, treatment median from days while achieving notable 1‐log10 order burden. Overall, our study underscores potent broad‐spectrum mouse infection hinting at their promising therapeutic potential disease.

Язык: Английский

Hydroethanolic Extract of Punica granatum Inhibits Cryptococcus by Depolarising Mitochondrial Membranes DOI Creative Commons
Julliana Ribeiro Alves dos Santos, Brenda Letícia Araujo Motta, Haryne Lizandrey Azevedo Furtado

и другие.

Microbiology Research, Год журнала: 2025, Номер 16(2), С. 49 - 49

Опубликована: Фев. 16, 2025

Cryptococcal infections are distributed worldwide and mainly caused by Cryptococcus neoformans gattii. The reduced number of antifungals increasing cases resistance require the search for new therapeutic options, such as natural products. Among these, Punica granatum L. has demonstrated antifungal activity. present study aimed to evaluate in vitro activity hydroethanolic extract leaf P. (HEPg) alone or combination against C. gattii interference mitochondrial membrane using flow cytometry. minimum inhibitory concentration was determined, which showed isolates. fractional resulted an indifferent interaction between amphotericin B + HEPg, whereas fluconazole HEPg synergistic depolarisation membranes more pronounced when previously treated with granatum, either individually agents. In contrast, prior treatment promoted hyperpolarisation membranes. Considering growing alternative forms cryptococcosis, this highlights potential granatum.

Язык: Английский

Процитировано

0
Therapeutic Role of Fluconazole in Immunocompetent Patients with Pulmonary Cryptococcosis: A Case Report DOI Creative Commons
Huimin Yu, Shuang Hua,

Qifei Sha

и другие.

IDCases, Год журнала: 2025, Номер 40, С. e02188 - e02188

Опубликована: Янв. 1, 2025

The present investigation examines the potential for customized treatment of pulmonary cryptococcosis using fluconazole in an immunocompetent individual. Therapeutic drug monitoring (TDM) was utilized throughout to assess levels. Research indicated that MIC90 cryptococcus China is around 8 mg/L. We evaluated area under curve (AUC) relative minimal inhibitory concentration (MIC), focusing on AUC from 0 24 h (AUC0-24 h/MIC). Fluconazole's dosage adjusted according pharmacokinetics/pharmacodynamics (PK/PD) principles enhance therapeutic efficacy. Post-treatment evaluation showed marked improvement patient's condition, with lesions exhibiting partial absorption.

Язык: Английский

Процитировано

0
Fluconazole Resistance and Heteroresistance in Cryptococcus spp.: Mechanisms and Implications DOI Creative Commons
Izabela de Mesquita Bárcia Moreira, Edinaira Sulany Oliveira de Sousa, Juan Diego Ribeiro de Almeida

и другие.

Revista da Sociedade Brasileira de Medicina Tropical, Год журнала: 2025, Номер 58

Опубликована: Янв. 1, 2025

ABSTRACT The reference methodology for evaluating antifungal susceptibility is based on determining the minimum inhibitory concentration (MIC), which lowest drug capable of inhibiting fungal growth. However, such MIC data are insufficient to measure if a strain heteroresistant tested drug. In cases, minority subpopulation cells, originating from an initially susceptible lineage, can grow at concentrations above MIC. studies fluconazole heteroresistance in Cryptococcus spp., chromosomal disomy has been shown result overexpression two genes located chromosome 1 (Chr1) linked resistance: ERG11 and AFR1. This review addresses underlying mechanisms resistance, evolution methods susceptibility, clinical implications fluconazole. analysis findings indicated correlation between adverse outcomes, although this observation still lacks definite confirmation literature. highlights need implement more efficient therapeutic strategies improve testing.

Язык: Английский

Процитировано

0
Emergence of Triazole-Resistant Cryptococcus neoformans after Exposure to Environmentally Relevant Concentrations of Difenoconazole in Liquid Medium and Soil DOI
Wenwen Peng,

Xiaoxiang Fu,

Hantao Yu

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

The rapid global emergence and spread of resistance to clinical triazoles in Cryptococcus neoformans have been associated with the use agricultural triazole fungicides. However, there is no direct evidence currently linking triazole-resistant C. (TRCN) strains application fungicides soil. This study investigated whether could be induced by difenoconazole, an fungicide, liquid medium Our findings reveal that environmentally relevant concentrations difenoconazole can drive cross-resistance through upregulation ERG11 efflux pump genes (AFR1, AFR3, MDR1). Notably, prevalence TRCN soil correlates residual levels, significantly more isolates observed at two- five-fold recommended dose than standard dose. These results provide highlight importance applying or below dosage mitigate development environments. addresses a critical gap understanding environmental drivers underscores need for responsible fungicide prevent resistant pathogens.

Язык: Английский

Процитировано

0
Enhancing Antifungal Drug Discovery Through Co-Culture with Antarctic Streptomyces albidoflavus Strain CBMAI 1855 DOI Open Access
Ana Luisa Perini Leme Giordano, Marili Villa Nova Rodrigues, Kamila Reis Santos

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12744 - 12744

Опубликована: Ноя. 27, 2024

Fungal infections pose a growing public health threat, creating an urgent clinical need for new antifungals. Natural products (NPs) from organisms in extreme environments are promising source novel drugs. Streptomyces albidoflavus CBMAI 1855 exhibited significant potential this regard. This study aimed to (1) assess the antifungal spectrum of extract against key human pathogens, (2) elicit NP production through co-cultivation with fungi, correlating metabolites biosynthetic gene clusters (BGCs), and (3) perform silico toxicity predictions identified compounds analyze their suitability drug development. The crude broad-spectrum activity. metabolomic analysis NPs such as antimycin A, fungimycin, surugamides, 9-(4-aminophenyl)-3,7-dihydroxy-2,4,6-trimethyl-9-oxo-nonoic acid, ikarugamycin, latter two predicted be most suitable Genome mining revealed three cryptic BGCs potentially encoding These warrant detailed investigation elucidate metabolic harness potential. is prolific producer multiple agents, offering valuable discovery. highlights importance exploring microbial interactions uncover therapeutics fungal infections, exploration pathway compounds.

Язык: Английский

Процитировано

1
Late Relapse of Previous Pulmonary Cryptococcosis With Symptoms Resembling Cerebral Infarction: A Case Report DOI Creative Commons
Anatoli Pinchuk, Gernot Geginat, Volker Rickerts

и другие.

Case Reports in Infectious Diseases, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

Cryptococcosis, an infection caused by Cryptococcus neoformans and gattii , predominantly targets the central nervous system (CNS) in patients with AIDS but is not limited to this group. The disease can also occur individuals various immunosuppressive conditions, frequently involving brain or lungs. Cryptococcal meningitis (CM) most common form of fungal meningoencephalitis, leading intracerebral infections, cerebral infarction, hydrocephalus. clinical presentation CM nonspecific, imaging features vary significantly. This case report presents a patient who was HIV‐negative had been on long‐term cortisone therapy. Notably, history pulmonary cryptococcosis 15 years prior involvement. When initially at our clinic, histology culture results from biopsies were negative earlier unknown. Subsequently, cryptococcal antigen detected both serum cerebrospinal fluid (CSF), C. cultivated CSF. highlights critical importance maintaining high index suspicion for CM, particularly previous it demonstrates possibility false‐negative biopsy due secondary vascular events associated CM.

Язык: Английский

Процитировано

0
Development of ptxD /Phi as a new dominant selection system for genetic manipulation in Cryptococcus neoformans DOI Creative Commons

Muthita Khongthongdam,

Tanaporn Phetruen,

Sittinan Chanarat

и другие.

Microbiology Spectrum, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

is a globally distributed pathogenic fungus posing significant threat to immunocompromised individuals, particularly those with HIV/AIDS. Effective genetic manipulation tools are essential for understanding its biology and developing new therapies. However, current tools, including the variation of versatile selectable markers, limited. This study develops validates phosphite dehydrogenase gene (

Язык: Английский

Процитировано

0
Efficacy of two novel antifungal lipopeptides, AF4 and AF5 of bacillomycin D family in murine models of invasive candidiasis, cryptococcosis, and aspergillosis DOI Creative Commons
Raees A. Paul,

Madhuri Madduri,

Nisha Kashyap

и другие.

Apmis, Год журнала: 2024, Номер 133(1)

Опубликована: Дек. 25, 2024

Invasive fungal diseases are an important public health concern due to increase in the at‐risk population and high mortality associated with these infections. Managing invasive infections poses a significant challenge given limited antifungal options emergence of resistance key pathogens. Through comprehensive approach, we evaluated vitro activity vivo efficacy two novel lipopeptides, AF 4 5 murine models disseminated candidiasis, cryptococcosis, aspergillosis. Flow cytometry analysis propidium iodide showed dose‐dependent permeability disruption cell membranes, underscoring membrane perturbing effects . These observations were further substantiated by SEM analyses that yeast hyphal deformation leakage cellular contents. Our investigations utilizing doses (5 10 mg/kg bodyweight) each lipopeptide its comparison standard therapies lipopeptides significantly improved odds mice survival candidiasis cryptococcosis models, reduction organ burden 2 3‐log order. Additionally, aspergillosis model, treatment median from days while achieving notable 1‐log10 order burden. Overall, our study underscores potent broad‐spectrum mouse infection hinting at their promising therapeutic potential disease.

Язык: Английский

Процитировано

0