Dataset Information

Characterization of pathogenic Candida glabrata and their effectiveness against systemic candidiasis in BALB/c mice

ABSTRACT: Candida glabrata is a common opportunistic fungal pathogen of humans, with the emergence of resitant strains being of particulary concern. The cell wall associated and secretory proteins are intrinsically involved in vital functions during the fungal-host interactions. These proteins are responsible for eliciting immune response in host during candidiasis and therefore can be a promising candidates for vaccine development. BALB/c mice were broadly divided into unimmunized, immunized groups and the designated groups were immunized with β-mercaptoethanol (β-ME) call wall extract, and secretory protein extract from C. glabrata via intraperitoneal route. All the animals were then challenged with a lethal dose of C. glabrata. Furthermore, we applied a liquid chromatography-tandem mass spectrometry (LC–MS/MS) -based approach for the characterization of β-ME extract and secretory protein extract from C. glabrata, which resulted in a comprehensive cell wall and secretory proteome map.portunistic fungal pathogen of humans, with the emergence of resitant strains being of particulary concern. The cell wall associated and secretory proteins are intrinsically involved in vital functions during the fungal-host interactions. These proteins are responsible for eliciting immune response in host during candidiasis and therefore can be a promising candidates for vaccine development. BALB/c mice were broadly divided into unimmunized, immunized groups and the designated groups were immunized with β-mercaptoethanol (β-ME) call wall extract, and secretory protein extract from C. glabrata via intraperitoneal route. All the animals were then challenged with a lethal dose of C. glabrata. Furthermore, we applied a liquid chromatography-tandem mass spectrometry (LC–MS/MS) -based approach for the characterization of β-ME extract and secretory protein extract from C. glabrata, which resulted in a comprehensive cell wall and secretory proteome map.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Candida Glabrata (yeast) (torulopsis Glabrata)

SUBMITTER: Previn Naicker

LAB HEAD: Stoyan Stoychev

PROVIDER: PXD032928 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

Characterization of the Secretome of Pathogenic Candida glabrata and Their Effectiveness against Systemic Candidiasis in BALB/c Mice for Vaccine Development.

Kamli Majid Rasool MR Sabir Jamal S M JSM Malik Maqsood Ahmad MA Ahmad Aijaz A

Pharmaceutics 20220921 10

Infections by non-albicans Candida species have increased drastically in the past few decades. Candida glabrata is one of the most common opportunistic fungal pathogens in immunocompromised individuals, owing to its capability to attach to various human cell types and medical devices and being intrinsically weakly susceptible to azoles. Immunotherapy, including the development of antifungal vaccines, has been recognized as an alternative approach for preventing and treating fungal ...[more]

PMID: 36297425

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Project description:Rationale: The diagnosis of idiopathic pulmonary fibrosis (IPF) requires exclusion of an underlying autoimmune disease, as present in interstitial lung diseases associated with connective tissue diseases (CTD-ILD). The prevalence of autoantibodies in IPF patients is currently unknown. Objectives: An unbiased assay for de novo discovery of autoantigens can help characterizing autoreactivities in IPF patients beyond clinically established autoimmune panels. Methods: We developed the proteomic Differential Antigen Capture (DAC) assay, capturing patient antibodies from plasma, followed by affinity purification coupled to mass spectrometry (AP-MS). The DAC assay quantifies the binding capacity of patient antibodies to proteins in a pooled native extract from lung explants (ILD explants n=41; donor controls n=12). Plasma antibodies from patients with IPF (n=35), CTD-ILD (n=24) and age-matched controls (n=32) were analyzed and validated in an independent cohort (IPF: n=40; CTD-ILD: n=20). Plasma antibody binding profiles were associated with clinical meta-data including diagnosis, lung function and transplant free survival. Measurements and Main Results: We identified 586 putative autoantigens in both study cohorts with a broad heterogeneity among disease entities and cohorts. On average, in IPF a mean±SD of 16±40 autoantigens and in CTD-ILD a mean±SD of 9±15 autoantigens were identified per patient. We identified 18 IPF-specific autoantigens validated in the second cohort. Interestingly, there was also a high number of shared autoantigens in IPF and CTD-ILD patients, with 17 being present in IPF and CTD-ILD of both cohorts. Presence of antibodies to Thrombospondin 1 (THBS1) and tubulin beta-1 chain (TUBB1) was associated with a significantly reduced survival in patients with IPF (p=0.002 and p=0.019, respectively). This signature was often associated with autoreactivity against talin-1 (TLN1), latent-transforming growth factor beta-binding protein 1 (LTBP1), epididymis secretory protein Li 112 (HEL-S-112), zyxin (ZYX), the LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) and caldesmon (CALD1). Conclusions: Unbiased proteomic profiling reveals that the overall prevalence of autoantibodies is similar in IPF and CTD-ILD patients and identifies novel IPF specific autoantigens associated with patient survival.

Dataset Information

Characterization of pathogenic Candida glabrata and their effectiveness against systemic candidiasis in BALB/c mice

Publications

Characterization of the Secretome of Pathogenic <i>Candida glabrata</i> and Their Effectiveness against Systemic Candidiasis in BALB/c Mice for Vaccine Development.

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