Silverman Sj

Bio: Silverman Sj is an academic researcher. The author has contributed to research in topics: Saccharomyces cerevisiae & Chitinase. The author has an hindex of 1, co-authored 1 publications receiving 137 citations.

Chitinase and chitin synthase 1: counterbalancing activities in cell separation of Saccharomyces cerevisiae.

Abstract: Summary: Previous results [E. Cabib, A. Sburlati, B. Bowers & S. J. Silverman (1989) Journal of Cell Biology 108, 1665-1672] strongly suggested that the lysis observed in daughter cells of Saccharomyces cerevisiae defective in chitin synthase 1 (Chs1) was caused by a chitinase that partially degrades the chitin septum in the process of cell separation. Consequently, it was proposed that in wild-type cells, Chs1 acts as a repair enzyme by replenishing chitin during cytokinesis. The chitinase requirement for lysis has been confirmed in two different ways: (a) demethylallosamidin, a more powerful chitinase inhibitor than the previously used allosamidin, is also a much better protector against lysis and (b) disruption of the chitinase gene in chs1 cells eliminates lysis. Reintroduction of a normal chitinase gene, by transformation of those cells with a suitable plasmid, restores lysis. The percentage of lysed cells in strains lacking Chs1 was not increased by elevating the chitinase level with high-copy-number plasmids carrying the hydrolase gene. Furthermore, the degree of lysis varied in different chs1 strains; lysis was abolished in chs1 mutants containing the scs1 suppressor. These results indicate that, in addition to chitinase, lysis requires other gene products that may become limiting.

Cell Wall Assembly in Saccharomyces cerevisiae

Abstract: An extracellular matrix composed of a layered meshwork of β-glucans, chitin, and mannoproteins encapsulates cells of the yeast Saccharomyces cerevisiae. This organelle determines cellular morphology and plays a critical role in maintaining cell integrity during cell growth and division, under stress conditions, upon cell fusion in mating, and in the durable ascospore cell wall. Here we assess recent progress in understanding the molecular biology and biochemistry of cell wall synthesis and its remodeling in S. cerevisiae. We then review the regulatory dynamics of cell wall assembly, an area where functional genomics offers new insights into the integration of cell wall growth and morphogenesis with a polarized secretory system that is under cell cycle and cell type program controls.

The Fungal Cell Wall : Structure, Biosynthesis, and Function

Abstract: The molecular composition of the cell wall is critical for the biology and ecology of each fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major cell wall components of fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of fungal walls. For similar reasons the enzymes that assemble fungal cell wall components are excellent targets for antifungal chemotherapies and fungicides. However, for fungal pathogens, the cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on fungal cell walls are moving from a descriptive phase defining the underlying genes and component parts of fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of cell walls and how the cell wall is targeted by immune recognition systems and the design of antifungal diagnostics and therapeutics.

Antifungal agents: chemotherapeutic targets and immunologic strategies.

Abstract: During the past two decades the frequencies and types of life-threatening fungal infections have increased dramatically in immunocompromised patients (7, 220, 232, 282). Several factors have contributed to this rise: the expansion of severely ill and/or immunocompromised patient populations with human immunodeficiency virus (HIV) infection, with chemotherapy-induced neutropenia, and receiving organ transplant-associated immunosuppressive therapy; more invasive medical procedures, such as extensive surgery and the use of prosthetic devices and vascular catheters; treatment with broad-spectrum antibiotics or glucocorticosteroids; parenteral nutrition; and peritoneal dialysis or hemodialysis (25, 63, 66). The major opportunistic pathogen has been Candida albicans (17, 25, 142); however, the frequency of non-C. albicans Candida species is increasing (232, 287). Invasive pulmonary aspergillosis is a leading cause of attributable mortality in bone marrow transplant recipients (209). HIV-infected patients are particularly susceptible to mucosal candidiasis, cryptococcal meningitis, disseminated histoplasmosis, and coccidioidomycosis (5, 66, 294), while Pneumocystis carinii pneumonia is a leading cause of death in HIV-infected patients in North America and Europe (121). P. carinii was considered, until recently, a protozoal parasite on the basis of its resistance to classical antifungal agents. However, it has been reclassified as being most closely related to ascomycetous fungi on the basis of rRNA and b-tubulin homologies, the presence of the typical fungal cell wall polymers glucan and chitin, and separate dihydrofolate reductase and thymidylate synthase enzymes (in protozoa, both activities reside on a single protein) (74, 163). Treatment of invasive mycoses is complicated by problems in diagnosis (285) and susceptibility testing (8, 79, 90, 230) of fungi. Opportunistic fungal infections are often treated empirically in profoundly neutropenic patients when there is fever of unknown origin refractory to broad-spectrum antibacterial agents (233, 266, 284). Treatment of deeply invasive fungal infections has consistently lagged behind bacterial chemotherapy (27, 178). Amphotericin B, still the ‘‘gold standard’’ for the treatment of most severe invasive fungal infections, was discovered in 1956 (102). One reason for the slow progress is that, like mammalian cells, fungi are eukaryotes, and thus, agents that inhibit protein, RNA, or DNA biosynthesis have greater potential for toxicity. A second reason is that, until recently, the incidence of life-threatening fungal infections was perceived as being too low to warrant aggressive research by the pharmaceutical industry. In the past decade, however, there has been a major expansion in the number of antifungal drugs available (99). Nevertheless, there are still major weaknesses in their spectra, potencies, safety, and pharmacokinetic properties. This minireview briefly discusses the antifungal agents currently in clinical use. It then considers the use of promising new biochemical targets in fungi as well as host-based, immunological approaches as evolving strategies for antifungal therapy.

Chitinases of fungi and plants: their involvement in morphogenesis and host‐parasite interaction

Abstract: There has been a considerable amount of recent research aimed at elucidating the roles of chitinase in fungi and plants. In filamentous fungi and yeasts, chitinase is involved integrally in cell wall morphogenesis. Chitinase is also involved in the early events of host-parasite interactions of biotrophic and necrotrophic mycoparasites, entomopathogenic fungi and vesicular arbuscular mycorrhizal fungi. In plants, induction of chitinase and other hydrolytic enzymes is one of a coordinated, often complex and multifaceted defense mechanism triggered in response to phytopathogen attack. Chitinase induction in plants is not considered solely as an antifungal resistance mechanism. Plant chitinases can be induced by various abiotic factors as well and there is some circumstantial evidence to suggest a morphogenetic role despite the apparent absence of the substrate in plant cells. Finally, some chitinases and other chitin-binding proteins including some plant lectins share chitin-binding domains as part of their molecular structure and provide fuel for the so-called ‘lectin-chitinase’ debate and speculation for the origin of chitinase in plants.