Yeast Killer Toxin-Like Candidacidal Ab6 Antibodies Elicited through the Manipulation of the Idiotypic Cascade

Polonelli, Luciano; Beninati, Concetta; Teti, Giuseppe; Felici, Franco; Ciociola, Tecla; Giovati, Laura; Sperindè, Martina; Passo, Carla Lo; Pernice, Ida; Domina, Maria; Arigò, Milena; Papasergi, Salvatore; Mancuso, Giuseppe; Conti, Stefania; Magliani, Walter

doi:10.1371/journal.pone.0105727

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…Hydrolysis and fractionation techniques used routinely to determine the polysaccharide content of the sugar of interest have demonstrated that not even trace amounts of di-, tri-, or tetrasaccharides are observed in pustulan, indicating that the molecule is linear in nature and contains exclusive ␤-1,6 glucan linkages (21). Other researchers have routinely used pustulan to study ␤-1,6 glucan-C-type lectin receptor (CLR) interactions and yeast ␤-1,6 glucan cell wall biology (22)(23)(24)(25)(26).…”

Section: Methodsmentioning

confidence: 99%

Evidence for Proinflammatory β-1,6 Glucans in the Pneumocystis carinii Cell Wall

et al. 2015

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Inflammation is a major cause of respiratory impairment during Pneumocystis pneumonia. Studies support a significant role for cell wall ␤-glucans in stimulating inflammatory responses. Fungal ␤-glucans are comprised of D-glucose homopolymers containing ␤-1,3-linked glucose backbones with ␤-1,6-linked glucose side chains. Prior studies in Pneumocystis carinii have characterized ␤-1,3 glucan components of the organism. However, recent investigations in other organisms support important roles for ␤-1,6 glucans, predominantly in mediating host cellular activation. Accordingly, we sought to characterize ␤-1,6 glucans in the cell wall of Pneumocystis and to establish their activity in lung cell inflammation. Immune staining revealed specific ␤-1,6 localization in P. carinii cyst walls. Homology-based cloning facilitated characterization of a functional P. carinii kre6 (Pckre6) ␤-1,6 glucan synthase in Pneumocystis that, when expressed in kre6-deficient Saccharomyces cerevisiae, restored cell wall stability. Recently synthesized ␤-1,6 glucan synthase inhibitors decreased the ability of isolated P. carinii preparations to generate ␤-1,6 carbohydrate. In addition, isolated ␤-1,6 glucan fractions from Pneumocystis elicited vigorous tumor necrosis factor alpha (TNF-␣) responses from macrophages. These inflammatory responses were significantly dampened by inhibition of host cell plasma membrane microdomain function. Together, these studies indicate that ␤-1,6 glucans are present in the P. carinii cell wall and contribute to lung cell inflammatory activation during infection. P neumocystis organisms are opportunistic fungi that produce significant morbidity and mortality in immunocompromised hosts, with infection-related fatalities ranging between 10% and 45% (1). Pneumocystis jirovecii is the species known to infect humans, while Pneumocystis carinii represents the parallel species studied widely in rodents (2). Pneumocystis pneumonia remains a significant cause of mortality during AIDS, despite highly active antiretroviral therapy (3-5). Severe Pneumocystis pneumonia is characterized by intense lung inflammation involving CD8 ϩ cells and neutrophils, impairing gas exchange (6-9).The P. carinii cell walls contain abundant ␤-glucan molecules (10). Fungal cell wall ␤-glucans are homopolymers of D-glucose consisting of ␤-1,3 core chains with variable numbers of ␤-1,6 glucose side chains. The variable inflammatory activities of different glucan preparations have been postulated to be related to the relative amounts and configurations of these two major structures (␤-1,3 versus ␤-1,6) (11). Almost all of the initial studies in fungi have largely focused on unfractionated glucans (10). In fact, all prior studies in P. carinii previously utilized only unfractionated ␤-1,3/␤-1,6 glucans. Interestingly, recent investigations in Saccharomyces cerevisiae indicate major roles for ␤-1,6 glucans in strongly mediating cellular activation and inflammation (11). Our investigations of unfractionated P. carinii ␤-glucans indicate that innate ...

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Section: Methodsmentioning

confidence: 99%

Evidence for Proinflammatory β-1,6 Glucans in the Pneumocystis carinii Cell Wall

et al. 2015

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“…The so-called “antibiobodies” (antibiotic-like antibodies) showed direct fungicidal effects without the intervention of other factors [ 162 ]. Through the immunization of rats and mice against mAbKT4, other monoclonal antibiobodies were obtained, as well as peptides that occur during the idiotypic cascade (mAb K10 and mAb K20) and single-chain fragments (scFv) [ 163 ]. In particular, from scFv H6.…”

Section: Killer Toxins: From a Competitive Advantage To The Applicmentioning

confidence: 99%

Bioprotective Role of Yeasts

2015

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The yeasts constitute a large group of microorganisms characterized by the ability to grow and survive in different and stressful conditions and then to colonize a wide range of environmental and human ecosystems. The competitive traits against other microorganisms have attracted increasing attention from scientists, who proposed their successful application as bioprotective agents in the agricultural, food and medical sectors. These antagonistic activities rely on the competition for nutrients, production and tolerance of high concentrations of ethanol, as well as the synthesis of a large class of antimicrobial compounds, known as killer toxins, which showed clearly a large spectrum of activity against food spoilage microorganisms, but also against plant, animal and human pathogens. This review describes the antimicrobial mechanisms involved in the antagonistic activity, their applications in the processed and unprocessed food sectors, as well as the future perspectives in the development of new bio-drugs, which may overcome the limitations connected to conventional antimicrobial and drug resistance.

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“…These mAbs that specifically reacting with killer toxins (KT) from Pichia anomala and Williopsis mrakii have broad antimicrobial spectrum and demonstrated in vitro similar activity to polymorphonuclear neutrophils against the hyphae and germinated conidia of A. fumigatus and in vivo protected immunocompromised mice with invasive aspergillosis from infection [143]. Similar results were observed against C. albicans in vitro and in vaginal and systemic murine models of candidiasis [144,145].…”

Section: Antibody-based Therapymentioning

confidence: 62%

Immunotherapy for Fungal Infections

Loreto¹,

Tondolo²,

Alves³

et al. 2017

Immunotherapy - Myths, Reality, Ideas, Future

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Opportunistic fungal infections are a major health problem being appointed by some studies as the fourth main cause of hospital-acquired infection in susceptible populations. The constantly growing incidences of these diseases are associated with the growing number of susceptible individuals, such as immunocompromised individuals (leukemia, AIDS, etc) and treatment-induced immunodeficiency (hematopoietic stem cell, solid organ transplant, anticancer therapy). Furthermore, other advances in medical care, patient's long-term hospitalization and antimicrobial therapies have created several vulnerable populations to fungal infections. Currently, antifungal drug therapies are several times inefficient, and the poor outcomes are linked to difficulties in the early diagnosis of fungal infections and drug resistance among fungal pathogens. In this context, novel therapeutic approaches are welcome to stimulate efficiently the host immune response to eliminate the fungal pathogen. This chapter is intended to review advances in immunotherapy strategies for fungal infections.

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Yeast Killer Toxin-Like Candidacidal Ab6 Antibodies Elicited through the Manipulation of the Idiotypic Cascade

Cited by 13 publications

References 41 publications

Evidence for Proinflammatory β-1,6 Glucans in the Pneumocystis carinii Cell Wall

Evidence for Proinflammatory β-1,6 Glucans in the Pneumocystis carinii Cell Wall

Bioprotective Role of Yeasts

Immunotherapy for Fungal Infections

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