Proteomics-driven design of a multiplex bead-based platform to assess natural IgG antibodies to pneumococcal protein antigens in children

Jiménez-Munguía, Irene; Wamel, Willem J. B. van; Olaya-Abril, Alfonso; García-Cabrera, Emilio; Rodríguez-Ortega, Manuel J.; Obando, Ignacio

doi:10.1016/j.jprot.2015.06.011

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…However, there is a general lack of metabolomic studies in bacteria, and particularly in the pneumococcus. In previous works, we have targeted the pneumococcal surface proteome aiming at the discovery of vaccine and/or diagnostic candidates 1, 2, 31, 32 . Very recently, we have studied the effect of iron deprivation in two reference pneumococcal strains, using a combination of transcriptomics, proteomics and metabolomics, and have found correlations when integrating proteome and metabolome information (Jiménez-Munguía et al ., unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae

Mitsuwan

Olaya-Abril

Calderón-Santiago

et al. 2017

Sci Rep

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The emergence of antibiotic-resistant pathogenic bacteria is a healthcare problem worldwide. We evaluated the antimicrobial activity of rhodomyrtone, an acylphloroglucinol present in Rhodomyrtus tomentosa leaves, against the human Gram-positive pathogen Streptococcus pneumoniae. The compound exhibited pronounced anti-pneumococcal activity against a broad collection of clinical isolates. We studied the effects at the molecular level by integrated proteomic and metabolomic analysis. The results revealed alterations in enzymes and metabolites involved in several metabolic pathways including amino acid biosynthesis, nucleic acid biosynthesis, glucid, and lipid metabolism. Notably, the levels of two enzymes (glycosyltransferase and UTP-glucose-1-phosphate uridylyltransferase) and three metabolites (UDP-glucose, UDP-glucuronic acid and UDP-N-acetyl-D-galactosamine) participating in the synthesis of the pneumococcal capsule clearly diminished in the bacterial cells exposed to rhodomyrtone. Rhodomyrtone-treated pneumococci significantly possessed less amount of capsule, as measured by a colorimetric assay and visualized by electron microscopy. These findings reveal the utility of combining proteomic and metabolomic analyses to provide insight into phenotypic features of S. pneumoniae treated with this potential novel antibiotic. This can lead to an alternative antibiotic for the treatment of S. pneumoniae infections, because of the growing concern regarding antimicrobial resistance.

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Section: Discussionmentioning

confidence: 99%

Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae

Mitsuwan

Olaya-Abril

Calderón-Santiago

et al. 2017

Sci Rep

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“…Loss of PspA did not alter the acquisition of sIgA to the bacterial surface. PspA, PspC, and pilus-1 are immunogenic in humans, and antibodies against these surface factors, which likely result from prior exposure during colonization episodes, are common (30)(31)(32)(33)(34). Therefore, we also analyzed the binding of IgG in hNF to Spn and found no significant difference between WT Spn and the protein-deficient mutants.…”

Section: Introductionmentioning

confidence: 94%

Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1

Binsker¹,

Lees²,

Hammond³

et al. 2020

Journal of Clinical Investigation

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“…The median interval of serum sample collection was 19 days ([25th-75th percentile]: 16-24 days). The positive control group was younger than the negative controls (median [25th-75th percentile]: 14 [9.5-24.5] vs.37 [25-48] months; P b 0.001), and there was no statistical difference on serum sample collection interval between the two groups (median [25th-75th percentile]: 20 [16.5-25.5] vs.18 (Turner and Turner, 2013;Olaya-Abril et al, 2015;van der Poll and Opal, 2009;Giefing et al, 2008;Jiménez-Munguía et al, 2015;Holmlund et al, 2009;Lebon et al, 2011;Simell et al, 2009;Hagerman et al, 2013) days; P = 0.6) and on the gender (76.9% vs. 43.5% of males, P = 0.052). The baseline antibody levels were higher in the negative control group for Ply, CbpA, PcpA, PhtD and StkP-C (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the development of multiplex techniques has allowed the test of multiple antigens in the same assay (Andrade et al, 2014), representing a more economic option when a combination of antigens is used to improve the overall sensitivity of the test. Of note, multiplex assays including up to 64 pneumococcal antigens have been described, with good robustness and no effect from the multiplexing, representing a resourceful tool for the measurement of IgG against pneumococcal proteins (Jiménez-Munguía et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, Posfay-Barbe et al showed that the use of multiple antigens markedly improves the sensitivity of antibody response detection against S. pneumoniae, particularly if PcpA was included in the combination (Posfay-Barbe et al, 2011). Furthermore, Jiménez-Munguía et al also described that the levels of specific IgG against PcpA were three times lower in sera of children with pneumonia collected up to 10 days of disease, when compared to that of negative controls (Jiménez-Munguía et al, 2015). Similar results were found for the evaluation of antibody responses in a cohort of 690 children with non-severe community-acquired pneumonia, in which PcpA and PcsB were the antigens with the highest rate of antibody response detection (Borges et al, 2015).…”

Section: Tablementioning

confidence: 99%

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Serological diagnosis of pneumococcal infection in children with pneumonia using protein antigens: A study of cut-offs with positive and negative controls

Andrade

Borges

Ivaska

et al. 2016

Journal of Immunological Methods

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The etiological diagnosis of infection by Streptococcus pneumoniae in children is difficult, and the use of indirect techniques is frequently warranted. We aimed to study the use of pneumococcal proteins for the serological diagnosis of pneumococcal infection in children with pneumonia. We analyzed paired serum samples from 13 Brazilian children with invasive pneumococcal pneumonia (positive control group) and 23 Finnish children with viral pharyngitis (negative control group), all aged <5years-old. Children with pharyngitis were evaluated for oropharyngeal colonization, and none of them carried S. pneumoniae. We used a multiplex bead-based assay with eight proteins: Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP and PcsB. The optimal cut-off for increase in antibody level for the diagnosis of pneumococcal infection was determined for each antigen by ROC curve analysis. The positive control group had a significantly higher rate of ≥2-fold rise in antibody levels against all pneumococcal proteins, except Ply, compared to the negative controls. The cut-off of ≥2-fold increase in antibody levels was accurate for pneumococcal infection diagnosis for all investigated antigens. However, there was a substantial increase in the accuracy of the test with a cut-off of ≥1.52-fold rise in antibody levels for PcpA. When using the investigated protein antigens for the diagnosis of pneumococcal infection, the detection of response against at least one antigen was highly sensitive (92.31%) and specific (91.30%). The use of serology with pneumococcal proteins is a promising method for the diagnosis of pneumococcal infection in children with pneumonia. The use of a ≥2-fold increase cut-off is adequate for most pneumococcal proteins.

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Proteomics-driven design of a multiplex bead-based platform to assess natural IgG antibodies to pneumococcal protein antigens in children

Cited by 10 publications

References 24 publications

Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae

Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae

Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1

Serological diagnosis of pneumococcal infection in children with pneumonia using protein antigens: A study of cut-offs with positive and negative controls

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