Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation.

Identification of pathways controlling DNA damage induced mutation in Saccharomyces cerevisiae.

Mutation in response to most types of DNA damage is thought to be mediated by the error-prone sub-branch of post-replication repair and the associated translesion synthesis polymerases. To further understand the mutagenic response to DNA damage, we screened a collection of 4848 haploid gene deletion strains of Saccharomyces cerevisiae for decreased damage-induced mutation of the CAN1 gene. Through extensive quantitative validation of the strains identified by the screen, we identified ten genes, which included error-prone post-replication repair genes known to be involved in induced mutation, as well as two additional genes, FYV6 and RNR4.

Interaction of amphotericin B lipid formulations and triazoles with human polymorphonuclear leucocytes for antifungal activity against Zygomycetes.

The frequency of zygomycosis has increased considerably over recent years mainly in immunocompromised and diabetic patients. Little is known about the effects of host innate immunity against different Zygomycetes especially under the influence of antifungal agents. The antifungal activity of human polymorphonuclear leucocytes (PMN) in combination with liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), voriconazole (VRC) and posaconazole (PSC) against Rhizopus oryzae and Rhizopus microsporus, frequently isolated Zygomycetes, were studied and compared with Absidia corymbifera, a less pathogenic Zygomycete.

Inteferon gamma and granulocyte-macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes against Scedosporium spp.: comparison with Aspergillus spp.

While Aspergillus spp. have been the most frequent filamentous fungi causing infections in immunocompromised patients, Scedosporium spp. are emerging as life-threatening pathogens.

Effects of interleukin-15 on antifungal responses of human polymorphonuclear leukocytes against Fusarium spp. and Scedosporium spp.

Fusarium spp. and Scedosporium spp. have emerged as important fungal pathogens that are frequently resistant to antifungal compounds.

Effect of media composition and in vitro activity of posaconazole, caspofungin and voriconazole against zygomycetes.

Objectives: The effect of different media and composition on the in vitro activity of posaconazole, caspofungin and voriconazole against 59 zygomycetes species was determined.

Methods: The media tested were RPMI 1640 medium with and without 2% glucose, antibiotic medium 3 (AM3) with and without 2% glucose, and high resolution (HR) medium.

Results: Posaconazole was significantly more active than caspofungin and voriconazole, both in RPMI 1640 medium with 2% glucose and in HR medium.

Interferon- gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes.

Zygomycetes cause serious invasive infections, predominantly in immunocompromised and diabetic patients with poor prognoses and limited therapeutic options. We compared the antifungal function of human polymorphonuclear leukocytes (PMNLs) against hyphae of Rhizopus oryzae and R. microsporus, the most frequently isolated zygomycetes, with that against the less frequently isolated Absidia corymbifera.

Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity.

The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells. Here we analyzed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and patients with arginase I deficiency, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of proinflammatory and anti-inflammatory stimuli in vitro.

Effects of several antifungal drug combinations against clinical and environmental isolates of Cryptococcus neoformans from China.

The in vitro interactions of caspofungin (CSP) with terbinafine (TRB) and ravuconazole (RVC) with 5-fluorocytosine (5-FC) were tested against 82 clinical and environmental isolates of Cryptococcus neoformans from China. The interaction of CSP with TRB proved synergistic against those isolates with a CSP MIC < or =2 microg ml-1 (5% of the isolates), additive against 42% of the isolates and indifferent against 53%. The effects of RVC with 5-FC were synergistic, additive or indifferent against 8%, 26% and 67% of the isolates, respectively.

Micafungin enhances neutrophil fungicidal functions against Candida pseudohyphae.

We evaluated the effect of the combination of micafungin and polymorphonuclear leukocytes (PMN) against hyphae of Candida albicans and Candida dubliniensis. Micafungin enhanced the PMN oxidative burst dose dependently. The combination was synergistic (C.

Interactions of human phagocytes with moulds Fusarium spp. and Verticillium nigrescens possessing different pathogenicity.

Fusarium spp. are emerging as important causes of invasive fungal infections. They tend to have decreased susceptibility to antifungal agents, making host defences very important.

Human phagocytic cell responses to Scedosporium apiospermum (Pseudallescheria boydii): variable susceptibility to oxidative injury.

Scedosporium apiospermum (Pseudallescheria boydii) is an emerging opportunistic filamentous fungus that causes serious infections in both immunocompetent and immunocompromised patients. To gain insight into the immunopathogenesis of infections due to S. apiospermum, the antifungal activities of human polymorphonuclear leukocytes (PMNs), mononuclear leukocytes (MNCs), and monocyte-derived macrophages (MDMs) against two clinical isolates of S.

Selective effects of interleukin (IL)-15 on antifungal activity and IL-8 release by polymorphonuclear leukocytes in response to hyphae of Aspergillus species.

The effects of interleukin (IL)-15 on human polymorphonuclear leukocyte (PMNL) activity against Aspergillus fumigatus and Aspergillus flavus were investigated. Pretreatment with IL-15 for 2 h increased PMNL oxidative burst, as measured by superoxide anion (O(2)(-)) release in response to A. fumigatus (P<.

Cytokines in immunodeficient patients with invasive fungal infections: an emerging therapy.

Immune response is the major contributor to host defense against opportunistic fungal infections such as candidiasis, aspergillosis and other rare infections. A number of cytokines have been developed and studied in vitro for activity against fungal pathogens. The most studied among them in relation to fungal infections are granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and interferon-gamma (IFN-gamma).

Amphotericin B lipid complex exerts additive antifungal activity in combination with polymorphonuclear leucocytes against Scedosporium prolificans and Scedosporium apiospermum.

Scedosporium prolificans and Scedosporium apiospermum are resistant to most antifungal agents and cause refractory pulmonary and disseminated infections. The combined effects of deoxycholate amphotericin B, amphotericin B lipid complex and liposomal amphotericin B with human polymorphonuclear leucocytes (PMNs) in damaging hyphae of these fungi were evaluated by XTT assay. Amphotericin B lipid complex displayed a significant additive effect with PMNs against both Scedosporium species (22% for S.

Antifungal triazoles and polymorphonuclear leukocytes synergize to cause increased hyphal damage to Scedosporium prolificans and Scedosporium apiospermum.

Scedosporium prolificans and Scedosporium apiospermum (Pseudallescheria boydii) cause pulmonary and disseminated infections refractory to most currently used antifungal agents in immunocompromised patients. We therefore investigated the potential antifungal activities of the triazoles itraconazole (ITC), voriconazole (VRC), and posaconazole (PSC) in combination with human polymorphonuclear leukocytes (PMNs) against the hyphae of these fungal pathogens. A colorimetric assay with (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide) sodium salt was used for the measurement of hyphal damage as an indicator of antifungal activity.

Amphotericin B formulations exert additive antifungal activity in combination with pulmonary alveolar macrophages and polymorphonuclear leukocytes against Aspergillus fumigatus.

Deoxycholate amphotericin B (DAMB) and amphotericin B lipid complex (ABLC) additively augmented the fungicidal activity of pulmonary alveolar macrophages against the conidia of Aspergillus fumigatus. DAMB, ABLC, and liposomal amphotericin B similarly displayed additive effects with polymorphonuclear leukocytes in damaging the hyphal elements of A. fumigatus.