Evaluation of the usefulness of anti-glyceraldehyde-3-phosphate dehydrogenase antibodies as a treatment for invasive candidiasis in a murine model

Gil, M. Luisa; Dagan, Shlomo; Eren, Rachel; Gozalbo, Daniel

doi:10.1007/s10482-005-9037-7

Cited by 12 publications

(11 citation statements)

References 22 publications

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“…The Poor Prognosis-Associated, Risk Antibodies in the ICPS are Directed to Potential Candida Proapoptotic Mediators-Although the mechanisms by which antibodies to Gap1p/Tdh3p and Ssb1p may negatively affect the clinical outcome of IC patients are unclear, earlier studies strengthen our results (62,63,65,87). Passive transfer and immunization assays in animal models have shown that anti-Gap1p/Tdh3p antibodies are neither protective nor can they stimulate protective responses against IC (62,63).…”

Section: The Biologic Relevance Of the Antibodies Included In The Icpsupporting

confidence: 64%

“…In addition to the five recombinant C. albicans protein dots, each immunoarray included negative (C-; bovine serum albumin) and positive (Cϩ; C. albicans protein extract) control dots to monitor experimental performance. Numbers above each pattern indicate tective antibodies, such as those to Hsp90p, Eno1p, Met6p, or Fba1p (13, 15, 56 -62), whereas the poor-prognosis signature was associated with undetectable/lower levels of them (possibly insufficient to induce protection (55)) and higher levels of nonprotective antibodies, like those to Gap1p/Tdh3p (62,63) or Ssa4p, Ssb1p or Ssc1p (cell wall-exposed, Hsp70p family members (42,64)). The latter is gathered from the nonprotective effect of anti-surface Hsp70p antibodies (65) and their high homology degree (see below).…”

Section: Fig 9 Prognostic Performance Of the Multiplexed Immunoassamentioning

confidence: 99%

“…Passive transfer and immunization assays in animal models have shown that anti-Gap1p/Tdh3p antibodies are neither protective nor can they stimulate protective responses against IC (62,63). Likewise, not only does immunization with a surface-exposed Hsp70p induce nonpro-tective responses against IC, but it may also play an apparent role in accelerating the animal's death (65).…”

Section: The Biologic Relevance Of the Antibodies Included In The Icpmentioning

confidence: 99%

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Prediction of the Clinical Outcome in Invasive Candidiasis Patients Based on Molecular Fingerprints of Five Anti-Candida Antibodies in Serum

Pitarch

Nombela

Gil

2011

Molecular & Cellular Proteomics

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Better prognostic predictors for invasive candidiasis (IC) are needed to tailor and individualize therapeutic decisionmaking and minimize its high morbidity and mortality. We investigated whether molecular profiling of IgG-antibody response to the whole soluble Candida proteome could reveal a prognostic signature that may serve to devise a clinical-outcome prediction model for IC and contribute to known IC prognostic factors. By serological proteome analysis and data-mining procedures, serum 31-IgG antibody-reactivity patterns were examined in 45 IC patients randomly split into training and test sets. Within the training cohort, unsupervised two-way hierarchical clustering and principal-component analyses segregated IC patients into two antibody-reactivity subgroups with distinct prognoses that were unbiased by traditional IC prognostic factors and other patients-related variables. Supervised discriminant analysis with leave-one-out cross-validation identified a five-IgG antibody-reactivity signature as the most simplified and accurate IC clinical-outcome predictor, from which an IC prognosis score (ICPS) was derived. Its robustness was confirmed in the test set. Multivariate logistic-regression and receiver-operating-characteristic curve analyses demonstrated that the ICPS was able to accurately discriminate IC patients at high risk for death from those at low risk and outperformed conventional IC prognostic factors. Further validation of the five-IgG antibody-reactivity signature on a multiplexed immunoassay supported the serological proteome analysis results. The five IgG antibodies incorporated in the ICPS made biologic sense and were associated either with good-prognosis and protective patterns (those to Met6p, Hsp90p, and Pgk1p, putative Candida virulence factors and antiapoptotic mediators) or with poor-prognosis and risk patterns (those to Ssb1p and Gap1p/Tdh3p, potential Candida proapoptotic mediators). We conclude that the ICPS, with additional refinement in future larger prospective cohorts, could be applicable to reliably predict patient Despite recent advances in antifungal therapy, invasive candidiasis (IC) 1 remains a leading infectious cause of morbidity and mortality in cancer, postsurgical, and intensive care patients (1-3). Its significant impact on patient clinical outcome, as reflected in its increased attributable mortality (10%-49%), length of hospital stay (3-30 days per patient), and healthcare costs (US $ 6214 -92,266 per episode), could however be ameliorated if early and appropriate antifungal therapeutic strategies were administered (1, 4). This precondition highlights the need to search for prognostic features that may reliably predict the clinical outcome in IC patients at presentation to tailor and individualize therapeutic decision-making accordingly and, as a result, to minimize the burden of the invasive infections caused by Candida spp. (commonly Candida albicans (1)).Several factors have classically been reported to adversely influence the clinical outcome of IC patients (3, ...

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Section: The Biologic Relevance Of the Antibodies Included In The Icpsupporting

confidence: 64%

Section: Fig 9 Prognostic Performance Of the Multiplexed Immunoassamentioning

confidence: 99%

Section: The Biologic Relevance Of the Antibodies Included In The Icpmentioning

confidence: 99%

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Prediction of the Clinical Outcome in Invasive Candidiasis Patients Based on Molecular Fingerprints of Five Anti-Candida Antibodies in Serum

Pitarch

Nombela

Gil

2011

Molecular & Cellular Proteomics

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“…Vesicle transportation could explain the reason by which some nuclear and cytosol proteins are detected in cell wall and culture medium. For instance, proteins such as enolase (Karkowska‐Kuleta et al ., ), glyceraldehyde‐3‐phosphate dehydrogenase (Gpdh) (Gil et al ., ), fructose‐bisphosphate aldolase (Pitarch et al ., ), triosephosphate isomerase (Tpi), phosphoglycerate kinase (Pgk) (Karkowska‐Kuleta et al ., ) and phosphoglycerate mutase (Crowe et al ., ; Karkowska‐Kuleta et al ., ) all play key roles in the glycolytic pathway and are detected at the C. albicans cell wall. Notably, enolase, Gpdh, Tpi, Pgk and the glycosyl hydrolase Bgl2, all components of C. albicans EV, elicit human antibodies in systemic candidiasis (Pitarch et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Compositional and immunobiological analyses of extracellular vesicles released byCandida albicans

et al. 2014

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SummaryThe release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow-derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850 nm. Two predominant seroreactive proteins (27 kDa and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin-layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)-12, transforming growth factor-beta (TGF-β) and IL-10. Similarly, EV-treated DC produced IL-12p40, IL-10 and tumour necrosis factor-alpha. In addition, EV treatment induced the up-regulation of CD86 and major histocompatibility complex class-II (MHC-II). Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.

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“…However, a study on its potential immunotherapeutic use showed that antibodies against Gap1p did not confer protection in murine model of systemic candidiasis (Gil et al . ).…”

Section: Discussionmentioning

confidence: 97%

Identification of immunogenic proteins of Candida parapsilosis by serological proteome analysis

et al. 2014

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Aims Systemic candidiasis is the leading fungal bloodstream infection, and its incidence has been on the rise. Recently, Candida parapsilosis has emerged as an increasingly prevalent fungal pathogen, but little is known about its antigenic profile. Hence, the current work was performed to discover immunogenic proteins of C. parapsilosis using serological proteome analysis. Methods and Results Cell wall proteins extracted from C. parapsilosis were resolved by two‐dimensional electrophoresis followed by immunoblotting using antisera from experimentally infected mice. Mass spectrometry analysis of the 32 immunoreactive protein spots resulted in the identification of 12 distinct proteins. Among them, 11 proteins were known antigens of Candida albicans, whereas Idh2p was identified for the first time as an immunogenic protein of Candida species. Recombinant Idh2p was expressed in Escherichia coli, and its antigenicity was verified by immunoblot analysis. Conclusions An immunoproteomic approach was successfully applied to identify immunogenic proteins of C. parapsilosis, with Idh2p as a novel candidate antigen. The identified antigens may serve as potential biomarkers for development of diagnostic assay and/or vaccine for C. parapsilosis. Significance and Impact of the Study This work represents the first immunoproteomic analysis of C. parapsilosis, which provides new insights into host–pathogen interactions and pathogenesis of C. parapsilosis. The immunogenic proteins could be studied as biomarker candidates for C. parapsilosis.

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Evaluation of the usefulness of anti-glyceraldehyde-3-phosphate dehydrogenase antibodies as a treatment for invasive candidiasis in a murine model

Cited by 12 publications

References 22 publications

Prediction of the Clinical Outcome in Invasive Candidiasis Patients Based on Molecular Fingerprints of Five Anti-Candida Antibodies in Serum

Prediction of the Clinical Outcome in Invasive Candidiasis Patients Based on Molecular Fingerprints of Five Anti-Candida Antibodies in Serum

Compositional and immunobiological analyses of extracellular vesicles released byCandida albicans

Identification of immunogenic proteins of Candida parapsilosis by serological proteome analysis

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