Fig 1.
Top 25 most abundant proteins.
Heat map shows mean protein abundances from each replicate group. Controls, tissue extract-injection group (n = 4), Cases, egg-injection replicates (n = 4). Proteins are shown as Accession number | Description.
Fig 2.
Differential protein expression in the bladder tissue proteome between cases and controls.
a) Scores plot from principal component analysis (PCA) across samples, annotated by group. The explained variances are shown in brackets. b) Protein abundance dendrogram. From abundance data, the Euclidean distance was calculated, and samples were clustered based on distances (clustering algorithm–Ward’s linkage). c) Proteins identified by fold change (FC) analysis of case/control ratio with 1.2-FC threshold. Values are on a log scale to show both up-regulated (positive log scale) and down-regulated (negative log scale) proteins symmetrically. Pink symbols represent proteins above the 1.2-FC threshold. d) Volcano plot of differentially expressed proteins (DEPs, n = 45) as measured in bladder tissue. Plot is shown comparing protein abundance in egg-injected bladders relative to tissue extract-injected bladders (i.e., cases/controls). Pink symbols represent proteins above the 1.2-FC (log2FC = ±0.3) threshold and an FDR <0.05.
Fig 3.
a) Pattern correlation analysis of the 45 proteins (DEPs), showing increasing and decreasing patterns relative to S. haematobium egg status. Correlation coefficients indicate correlation pattern or protein abundance trends relative to the S. haematobium egg injection group. Pink and blue bars indicate a positive and negative correlation with S. haematobium egg-injection respectively. *, raw p <0.001 and FDR <0.05. b) Clustering and heatmap of significantly differentially expressed proteins among the S. haematobium egg-injection group (cases) and the tissue extract-injection group (controls). The heat map was created based on the mean relative abundance of the 45 significant differentially expressed proteins (distance measure using Euclidean, clustering algorithm–Ward’s linkage). Red class label indicates the case group, and the blue class label represents the control group.
Fig 4.
Bar plot showing Gene Ontology Analysis of differential expressed proteins.
a) the bar chart shows the distribution of corresponding GO terms. Different colors represent different GO categories. b) the bar chart shows corresponding GO terms based on fold change (FC) analysis of case/control ratio (see S11 Table for details).
Fig 5.
STRING analysis of protein-protein interaction (PPI).
Analysis was done considering significant differentially expressed proteins in bladder tissues of mice in the egg-injection group (cases) vs. the tissue extract-injection group (controls). Red nodes represent up-regulated proteins; blue nodes represent down-regulated proteins. Interactions include direct (physical) and indirect (functional) associations from computational prediction, from knowledge transfer between organisms, and from interactions aggregated from primary databases.
Fig 6.
Proposed model for the proteins modified during S. haematobium infections which may contribute to host pathology.
Created with BioRender.com
↑ STEAP4, Pla2g7, Dab2, Fkbp14, Stab1, Loxl2, Prpf3, Ltbp3, Nob1, Raly, Gpx8, ↓ Cryl1, Usp11, Gnao1, Grhpr, Ppp1r14a, Hopx, Gas1, Cbr1, Bcl-2) associated with increased cell proliferation and decreased tumor suppression, contributing to carcinogenesis. ↑ Rps9, Rpl5, Rpl26, Rps13, Rps3a, Rpl23 associated with increased protein translation, collagen transcription and granuloma formation, as well as urothelial hyperplasia. ↑ Casp3, ↓ Bcl-2 in addition to secreted soluble egg antigens (SEA) associated with increased apoptosis and switch in immune responses from Th1 to Th2. ↑ Dab2, STEAP4, Prpf3, Pecam1 and Serpina3n may promote Th2 differentiation, and infiltrating levels of macrophages, neutrophils, dendritic cells, and T-cells, also relevant for granuloma, tissue repair and wound healing. ↓ Itgb3, Itga1, Itga7, Armc1, Usp11, Dmd, Mapre3 reduce cell-cell adhesions and facilitate egg shedding. ↑ Pla2g7 and Ptpn2 may be an adaptive oxidative stress response to promote epithelial barrier integrity.