Disease relevance of Histoplasma

• Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis [1].
• One patient who was much improved while receiving ketoconazole continued to harbor Histoplasma capsulatum in an abdominal aortic aneurysm, which became symptomatic 4 months after cessation of the drug [2].
• In contrast to wild-type mice, perforin-deficient mice infected with lymphocytic choriomeningitis virus clone 13 and Histoplasma showed an absence of immunopathology, but the animals still died [3].
• To investigate the efficacy of combined treatment with fluconazole (Flu) and amphotericin B (AmB) for Histoplasma capsulatum meningitis, MICs were determined for 10 clinical isolates, following National Committee for Clinical Laboratory Standards guidelines [4].
• Interleukin-12 neutralization alters lung inflammation and leukocyte expression of CD80, CD86, and major histocompatibility complex class II in mice infected with Histoplasma capsulatum [5].

High impact information on Histoplasma

• Possible role for cysteine biosynthesis in conversion from mycelial to yeast form of Histoplasma capsulatum [6].
• p-Chloromercuriphenylsulfonic acid (PCMS), a sulfhydryl inhibitor, prevented the mycelial-to-yeast transition of the dimorphic fungal pathogen, Histoplasma capsulatum [7].
• CD40 ligand is not essential for induction of type 1 cytokine responses or protective immunity after primary or secondary infection with histoplasma capsulatum [8].
• Longer-term studies using cells preincubated with acridine orange indicated that phagolysosomes containing live Histoplasma continued to maintain a relatively neutral pH for at least 30 h [9].
• Role of the adherence-promoting receptors, CR3, LFA-1, and p150,95, in binding of Histoplasma capsulatum by human macrophages [10].

Chemical compound and disease context of Histoplasma

• In two separate closed clinical trials that evaluated the efficacy of liposomal amphotericin B and itraconazole treatment of disseminated histoplasmosis in patients with AIDS, blood was cultured for fungus and blood and urine were tested for Histoplasma antigen [11].
• Its spectrum of activity is somewhat broader than that of fluconazole and it is clinically active against superficial mycoses and some of the infections caused by pathogenic fungi such as Histoplasma capsulatum [12].
• Itraconazole is the treatment of choice for non-life-threatening Histoplasma capsulatum or Blastomyces dermatitidis infections occurring in immunocompetent individuals and is the most efficient secondary prophylaxis of histoplasmosis in AIDS patients [13].
• Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis [14].
• Orbital histoplasmosis due to Histoplasma capsulatum var. duboisii: successful treatment with Septrin [15].

Biological context of Histoplasma

• Role of cysteine in regulating morphogenesis and mitochondrial activity in the dimorphic fungus Histoplasma capsulatum [16].
• The terminus of a Histoplasma linear plasmid was cloned and shown to contain multiple repeats of GGGTTA, the telomeric repeat unit also found in vertebrates, trypanosomes, and slime moulds [17].
• As an alternative to allelic replacement, we have developed a telomeric plasmid-based system for silencing gene expression in Histoplasma by RNA interference (RNAi) [18].
• Nitric oxide synthase expression in macrophages of Histoplasma capsulatum-infected mice is associated with splenocyte apoptosis and unresponsiveness [19].
• Additionally, a comparison of two Histoplasma strains carrying the CBP1 promoter fusion construct either epichromosomally or integrated into the chromosome revealed cell-to-cell variation in plasmid copy number due to uneven plasmid partitioning into daughter cells [20].

Anatomical context of Histoplasma

• DCs pulsed with microbial antigens (e.g., leishmania and histoplasma Ags) were capable of inducing proliferative responses in autologous CD4+ lymphocytes [21].
• HIS-62 is a glycoprotein that has been isolated from the cell wall and cell membrane fraction of the pathogenic fungus Histoplasma capsulatum [22].
• Pulmonary V beta 4+ T cells from Histoplasma capsulatum-infected mice respond to a homologue of Sec31 that confers a protective response [23].
• Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens, as measured by Histoplasma antigen detection techniques and quantitative cultures, for each comparison [24].
• Tumor necrosis factor-alpha was detected in supernatants collected from BALB/c mouse peritoneal macrophages incubated continuously with Histoplasma capsulatum [25].

Associations of Histoplasma with chemical compounds

• The antimalarial drug chloroquine accumulates inside the macrophage phagolysosome by ion trapping where it exerts potent antifungal activity against Histoplasma capsulatum and Cryptococcus neoformans by distinct mechanisms [26].
• Ketoconazole-responsive tonsillar infection due to Histoplasma capsulatum in an HIV-1-seropositive individual [27].
• At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and Fungizone groups had died [28].
• Hypothesis on the mechanism of resistance to fluconazole in Histoplasma capsulatum [29].
• Fungal burden assessed on survivors showed similar levels of Histoplasma antigen in lung and spleen homogenates of mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID [30].

Gene context of Histoplasma

• To demonstrate that IFN-gamma can induce these genes in vivo, mice were infected with Histoplasma capsulatum [31].
• Protective and memory immunity to Histoplasma capsulatum in the absence of IL-10 [32].
• Perforin is required for primary immunity to Histoplasma capsulatum [33].
• Regulation of infection with Histoplasma capsulatum by TNFR1 and -2 [34].
• RESULTS: Ten cases of Histoplasma capsulatum (HC) infection were reported: 9 associated with infliximab and 1 associated with etanercept [35].

Analytical, diagnostic and therapeutic context of Histoplasma

• Comparison of ketoconazole and amphotericin B in interference with thymidine uptake by and blastogenesis of lymphocytes stimulated with Histoplasma capsulatum antigens [36].
• Vaccination with recombinant (r) hsp60 protects mice against Histoplasma capsulatum [37].
• The electrophoretic mobility shift assay (EMSA) technique also detected protein(s) recognizing a pyrimidine-rich motif found in several Histoplasma promoters [38].
• Mice treated with nikkomycin Z at 20 and 100 mg/kg/dose BID had significantly higher CFUs per gram of organ weight in quantitative cultures and higher levels of Histoplasma antigen in lung and spleen homogenates than mice treated with amphotericin B at 2.0 mg/kg/dose QOD or itraconazole at 75 mg/kg/dose BID [30].
• Serum samples from 5 of 99 patients (5%) with other fungal infections and from 5 of 46 patients (11%) with tuberculosis had M precipitin bands by the Histoplasma immunodiffusion test, whereas none of the 123 sera from patients with other bacterial, Mycoplasma, or viral infections showed H or M precipitin bands [39].

References