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1.
Commun Biol ; 7(1): 704, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851817

ABSTRACT

Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates. Protein acetylation is a crucial post-translational modification that controls gene expression and biological processes. The strategic manipulation of enzymes involved in protein acetylation has emerged as a promising therapeutic approach for addressing fungal infections. Sirtuins, NAD+-dependent lysine deacetylases, regulate protein acetylation and gene expression in eukaryotes. However, their role in the human pathogenic fungus A. fumigatus remains unclear. This study constructs six single knockout strains of A. fumigatus and a strain lacking all predicted sirtuins (SIRTKO). The mutant strains are viable under laboratory conditions, indicating that sirtuins are not essential genes. Phenotypic assays suggest sirtuins' involvement in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. Deletion of sirE attenuates virulence in murine and Galleria mellonella infection models. The absence of SirE alters the acetylation status of proteins, including histones and non-histones, and triggers significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.


Subject(s)
Aspergillosis , Aspergillus fumigatus , Sirtuins , Aspergillus fumigatus/pathogenicity , Aspergillus fumigatus/genetics , Aspergillus fumigatus/enzymology , Sirtuins/genetics , Sirtuins/metabolism , Virulence , Animals , Mice , Aspergillosis/microbiology , Aspergillosis/drug therapy , Acetylation , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Virulence Factors/genetics , Virulence Factors/metabolism , Moths/microbiology
2.
Parasitol Int ; 66(2): 134-138, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28012796

ABSTRACT

This study aimed to evaluate the total extract of Taenia crassiceps metacestodes (TC) and its antigenic fractions obtained by Triton X-114 fractionation techniques, such as detergent (DC) and aqueous (AC), in the immunodiagnosis of human neurocysticercosis (NCC). Cerebrospinal fluid samples were divided into two groups: Group 1 (n=40), which was further divided into active (n=20) and inactive (n=20) NCC, and Group 2 (control group), which comprised 39 CSF samples from patients who had another neurological disorder, were suffering from other infectious diseases of the brain or had other parasitic infections. The total extracts and antigenic fractions were tested by enzyme-linked immunosorbent assay (ELISA) to detect human IgG anti-Taenia solium. T. crassiceps fractions (DC and AC) showed the same value of sensitivity (Se), 100%, for active and inactive NCC and a specificity (Sp) of 97.4%. The DS fraction obtained from T. solium showed 100% Se for active NCC, 95% Se for inactive NCC and a 92.3% Sp. The AS fraction obtained from T. solium showed 100% Se for both active and inactive NCC and a 94.9% Sp. There was a positive correlation between the total saline extract of T. crassiceps (TC) and T. solium (TS) and their fractions (DC, AC, DS and AS). Positive predictive value, negative predictive value, diagnostic efficiency and Youden index were calculated. In conclusion, these results demonstrated that detergent and aqueous fractions obtained from T. crassiceps metacestodes are important sources of specific antigens and are efficient for immunodiagnosis of active and inactive NCC.


Subject(s)
Antibodies, Helminth/cerebrospinal fluid , Antigens, Helminth/immunology , Antigens, Helminth/isolation & purification , Enzyme-Linked Immunosorbent Assay , Neurocysticercosis/diagnosis , Neurocysticercosis/immunology , Taenia/immunology , Animals , Antigens, Helminth/chemistry , Chemical Fractionation/methods , Female , Humans , Hydrophobic and Hydrophilic Interactions , Immunoglobulin G/cerebrospinal fluid , Larva/chemistry , Larva/immunology , Male , Mice , Neurocysticercosis/cerebrospinal fluid , Octoxynol , Polyethylene Glycols , Predictive Value of Tests , Sensitivity and Specificity , Sodium Chloride , Taenia/physiology
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