The Spr1875 protein confers resistance to the microglia-mediated killing of Streptococcus pneumoniae

Peppoloni, Samuele; Colombari, Bruna; Beninati, Concetta; Felici, Franco; Teti, Giuseppe; Speziale, Pietro; Ricci, Susanna; Ardizzoni, Andrea; Manca, Lidia; Blasi, Elisabetta

doi:10.1016/j.micpath.2013.04.002

Cited by 7 publications

(14 citation statements)

References 30 publications

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“…Visualization of the acidic Candida -containing phagosomes was performed as described previously ( 42 ), using the acidotropic dye LysoTracker Red DND-99 (Molecular Probes, Invitrogen) at a final concentration of 5 mM. The internalized Candida cells (no fluorescence) were visualized by epifluorescence microscopy (as opposed to bound/un-ingested yeast cells that showed a blue fluorescence because of the Uvitek 2B labeling).…”

Section: Methodsmentioning

confidence: 99%

Genomic and Phenotypic Variation in Morphogenetic Networks of Two Candida albicans Isolates Subtends Their Different Pathogenic Potential

et al. 2018

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The transition from commensalism to pathogenicity of Candida albicans reflects both the host inability to mount specific immune responses and the microorganism’s dimorphic switch efficiency. In this study, we used whole genome sequencing and microarray analysis to investigate the genomic determinants of the phenotypic changes observed in two C. albicans clinical isolates (YL1 and YQ2). In vitro experiments employing epithelial, microglial, and peripheral blood mononuclear cells were thus used to evaluate C. albicans isolates interaction with first line host defenses, measuring adhesion, susceptibility to phagocytosis, and induction of secretory responses. Moreover, a murine model of peritoneal infection was used to compare the in vivo pathogenic potential of the two isolates. Genome sequence and gene expression analysis of C. albicans YL1 and YQ2 showed significant changes in cellular pathways involved in environmental stress response, adhesion, filamentous growth, invasiveness, and dimorphic transition. This was in accordance with the observed marked phenotypic differences in biofilm production, dimorphic switch efficiency, cell adhesion, invasion, and survival to phagocyte-mediated host defenses. The mutations in key regulators of the hyphal growth pathway in the more virulent strain corresponded to an overall greater number of budding yeast cells released. Compared to YQ2, YL1 consistently showed enhanced pathogenic potential, since in vitro, it was less susceptible to ingestion by phagocytic cells and more efficient in invading epithelial cells, while in vivo YL1 was more effective than YQ2 in recruiting inflammatory cells, eliciting IL-1β response and eluding phagocytic cells. Overall, these results indicate an unexpected isolate-specific variation in pathways important for host invasion and colonization, showing how the genetic background of C. albicans may greatly affect its behavior both in vitro and in vivo. Based on this approach, we propose that the co-occurrence of changes in sequence and expression in genes and pathways driving dimorphic transition and pathogenicity reflects a selective balance between traits favoring dissemination of the pathogen and traits involved in host defense evasion. This study highlights the importance of investigating strain-level, rather than species level, differences, when determining fungal–host interactions and defining commensal or pathogen behavior.

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Section: Methodsmentioning

confidence: 99%

Genomic and Phenotypic Variation in Morphogenetic Networks of Two Candida albicans Isolates Subtends Their Different Pathogenic Potential

et al. 2018

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“…While the immune response to pneumococcus in the CNS is not sufficient to eradicate bacteria from the cerebrospinal fluid in the case of meningitis, it does appear to minimize parenchymal spread of disease as a complication of meningitis (Ribes et al, 2010). Microglia are able to phagocytose pneumococcus, but may not effectively kill the engulfed bacteria via phagosome acidification due to interference from surface protein Spr1875, a key immunogenic surface antigen recently identified in S. pneumoniae (Figure 6.2) (Peppoloni et al, 2013). Microglia are able to phagocytose pneumococcus, but may not effectively kill the engulfed bacteria via phagosome acidification due to interference from surface protein Spr1875, a key immunogenic surface antigen recently identified in S. pneumoniae (Figure 6.2) (Peppoloni et al, 2013).…”

Section: Streptococcus Pneumoniaementioning

confidence: 99%

“…Interestingly, pre-treatment of microglia with TLR-agonists, particularly TLR-9 agonists, enhances the ability of murine microglia to phagocytose and kill S. pneumoniae in in vitro studies, suggesting a possible therapeutic manipulation of these inflammatory responses (Ribes et al, 2010). Used with permission from Peppoloni et al (2013). Immunofluorescent staining of Iba-1 as marker for microglia (A) and GFAP as marker for astrocytes (B) in brain of mock treated mouse and during all the time points of pneumococcal infection.…”

Section: Streptococcus Pneumoniaementioning

confidence: 99%

Neuroglia in Infectious Brain Diseases

Skar¹

2015

Colloquium Series on Neuroglia in Biology and Medicine: From Physiology to Disease

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“…The goal of the work was to study immunogenicity and preventive effect of chimeric protein, composed of the fragments of three surface proteins of S. pneumoniae. The choice of conservative and immunogenic fragments of surface proteins PsaA, PspA and Spr1875 to include in the chimeric vaccine was based on previous studies, which reported their ability to induce protective antibodies [9][10][11][12][13]. PsaA is a highly conservative lipoprotein expressed by several serotypes and essential for virulence of S. pneumoniae [9].…”

Section: Introductionmentioning

confidence: 99%

“…PspA (Pneumococcal surface protein A) is a surface protein known to contribute to S. pneumonia virulence by binding human lactoferrin and by impeding complement activation in vivo and in vitro [10,11]. The surface protein Spr1875 (also known as LysM domain-containing protein) exhibits immunogenic properties and contributes to S. pneumoniae virulence due to its role in the development of pneumococcal meningitis [12,13]. Salmonella typhiurium flagelin FliC N-and C-terminal fragments known to interact with Toll-like receptor-5 (TLR-5) were included into the vaccine molecule as an activator of innate and adaptive immune responses [14,15].…”

Section: Introductionmentioning

confidence: 99%

Chimeric Protein PSPF, a Potential Vaccine for Prevention Streptococcus pneumoniae Infection

Suvorov¹,

Духовлинов²

2015

J Vaccines Vaccin

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A chimeric protein, designated PSPF (Pneumococcus Surface Proteins and Flagellin) was constructed from conservative and immunogenic fragments of S. pneumoniae surface proteins PspA, Spr1875, PsaA and the Salmonella typhiurium flagellin terminal domains FliC1, FliC2 functioning as adjuvant. PSPF was highly immunogenic in mice and induced protection from virulent S. pneumonia strains. All the subtypes of S. pneumoniae under study were recognized by anti-PSPF sera. Thus, the chimeric recombinant PSPF protein is a promising vaccine candidate for immunization of humans against S. pneumoniae.

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The Spr1875 protein confers resistance to the microglia-mediated killing of Streptococcus pneumoniae

Cited by 7 publications

References 30 publications

Genomic and Phenotypic Variation in Morphogenetic Networks of Two Candida albicans Isolates Subtends Their Different Pathogenic Potential

Genomic and Phenotypic Variation in Morphogenetic Networks of Two Candida albicans Isolates Subtends Their Different Pathogenic Potential

Neuroglia in Infectious Brain Diseases

Chimeric Protein PSPF, a Potential Vaccine for Prevention Streptococcus pneumoniae Infection

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