Journal: Science Advances

Article Title: Ptpn2 limits plasma cell fate and antiviral immunity by integrating B cell receptor and IFN-γ signals in B cells

doi: 10.1126/sciadv.aec0162

Figure Lengend Snippet: All panels compare Ptpn2 fl/fl MB1-cre ( Ptpn2 BKO ) versus Ptpn2 wt/wt MB1-cre (Ctrl) mice. ( A ) Quantification of splenocyte numbers and representative photograph of spleens of 10-week-old mice of the indicated genotypes. ( B ) t-SNE clustering of splenic immune cell populations. Cell identities were assigned on the basis of surface marker expression (table S2). Total cell numbers used for each plot are indicated. NK cells, natural killer cells. ( C ) Frequencies of splenic immune cell subsets. Data are representative of at least two independent experiments. ( D ) Representative flow cytometry plots of splenic CD19 + B220 + CD93 − CD21/35 hi CD23 lo MZ and CD19 + B220 + CD93 − CD21/35 lo CD23 hi Fo B cells. ( E ) Proportions and absolute cell numbers of splenic MZ and Fo B cells. Data are representative of three pooled independent experiments. ( F ) Immunofluorescence staining for CD169 (blue), IgD (magenta), and IgM (yellow) of spleen sections of mice of the indicated genotypes. Scale bars, 100 μm. ( G ) Quantification of average splenic MZ thickness based on immunofluorescence staining. The thickness was measured from the CD169 + border to the IgM boundary. The average is representative of three follicles per mouse. Data are representative of two pooled independent experiments. ( H ) Schematic for immunization with heat-inactivated S. pneumoniae. I.V., intravenous. ( I ) Total serum levels of anti-phosphorylcholine IgM titers measured by ELISA 5 days postimmunization with S. pneumoniae . Mean ± SEM optical density (OD) values for serial dilutions are plotted. Data are representative of one of two independent experiments with similar results. Curves represent the mean response of n = 4 mice per genotype. Statistical analyses are done using an unpaired t test (A, E, and G), nonparametric test (C), and two-way ANOVA (I). ns, nonsignificant. * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001, and **** P ≤ 0.0001. Each dot represents a biological replicate.

Article Snippet: S. pneumoniae immunizations were performed by injecting 1 × 10 8 heat-killed S. pneumoniae cells (cat. no. tlrl-hksp, InvivoGen) intravenously via the tail vein.

Techniques: Marker, Expressing, Flow Cytometry, Immunofluorescence, Staining, Enzyme-linked Immunosorbent Assay

Journal: Nucleic Acids Research

Article Title: PhoP-regulated VirK acts as an accessory factor to maintain virulence in polymyxin-resistant Klebsiella pneumoniae

doi: 10.1093/nar/gkag290

Figure Lengend Snippet: Transcriptomic analysis of Mut-S in comparison to Kpn2146 strains. ( A ) Volcano map displaying the upregulated (red dots) and downregulated (yellow dots) genes between the Mut-S group and the control group. ( B ) Changes in the relative expression of the mgrB, phoP , and virK genes in the Mut-S strain compared with those in the WT strain. ( C )Changes in the virK gene expression in the Mut-S strain after supplementation with the mgrB gene. ( D ) Changes in phoP and virK gene expressions after phoP gene knockdown in the Mut-S strain. ( E ) Changes in the mgrB and virK gene expressions after the mgrB gene was complemented in the phoP knockout strain in Mut-S. ( F ) Changes in the phoP and virK gene expressions after the phoP gene was supplemented in the phoP knockout strains in Mut-S. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001.

Article Snippet: The effects of virK on bacterial pathogenicity were further evaluated in a mouse systemic infection model using virK mutants and complemented strains under K. pneumoniae ATCC BAA2146 (wild type) or Mut-S ( mgrB truncated strain) backgrounds.

Techniques: Comparison, Control, Expressing, Gene Expression, Knockdown, Knock-Out

Journal: Nucleic Acids Research

Article Title: PhoP-regulated VirK acts as an accessory factor to maintain virulence in polymyxin-resistant Klebsiella pneumoniae

doi: 10.1093/nar/gkag290

Figure Lengend Snippet: Transcriptomic analysis of Mut-S in comparison to Kpn2146 strains. ( A ) Volcano map displaying the upregulated (red dots) and downregulated (yellow dots) genes between the Mut-S group and the control group. ( B ) Changes in the relative expression of the mgrB, phoP , and virK genes in the Mut-S strain compared with those in the WT strain. ( C )Changes in the virK gene expression in the Mut-S strain after supplementation with the mgrB gene. ( D ) Changes in phoP and virK gene expressions after phoP gene knockdown in the Mut-S strain. ( E ) Changes in the mgrB and virK gene expressions after the mgrB gene was complemented in the phoP knockout strain in Mut-S. ( F ) Changes in the phoP and virK gene expressions after the phoP gene was supplemented in the phoP knockout strains in Mut-S. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001.

Article Snippet: During preliminary investigations of a polymyxin-resistant mutant (Mut-S) of K. pneumoniae ATCC BAA-2146 (Kpn2146) [ ], we detected highly upregulated expression of the Kpn2146:RS17285 gene.

Techniques: Comparison, Control, Expressing, Gene Expression, Knockdown, Knock-Out

Journal: Frontiers in Medicine

Article Title: Protective effects of the RAGE inhibitor azeliragon as a potential anti- Streptococcus pneumoniae therapeutic in sepsis models

doi: 10.3389/fmed.2026.1793580

Figure Lengend Snippet: Effects of azeliragon on the in vitro growth of S. pneumoniae . Dose–response relationships of S. pneumoniae ATCC 49619 (A) , S. pneumoniae 1057 (B) , and S. pneumoniae 1044 (C) following treatment with increasing concentrations of azeliragon. Bacterial growth was measured after 18 h of incubation and expressed as OD 600 . Effects of azeliragon on the growth kinetics of S. pneumoniae ATCC 49619 (D) , S. pneumoniae 1057 (E) , and S. pneumoniae 1044 (F) . Bacteria were cultured under control conditions or with different concentrations of azeliragon, and OD 600 was recorded at indicated time points to generate growth curves. Data were presented as mean ± SD. The experiments were performed with three independent biological replicates ( n = 3). “ns” represented no significant difference, ** p < 0.01.

Article Snippet: To further assess the effects of azeliragon on pneumococcal growth, the reference strain S. pneumoniae ATCC 49619 and two clinical isolates (1057 and 1044) were examined under different drug concentrations.

Techniques: In Vitro, Incubation, Bacteria, Cell Culture, Control

Journal: Frontiers in Medicine

Article Title: Protective effects of the RAGE inhibitor azeliragon as a potential anti- Streptococcus pneumoniae therapeutic in sepsis models

doi: 10.3389/fmed.2026.1793580

Figure Lengend Snippet: Time-kill activity and biofilm disruption effects of azeliragon against S. pneumoniae . Time-kill curves of S. pneumoniae ATCC 49619 (A) , S. pneumoniae 1057 (B) , and S. pneumoniae 1044 (C) treated with azeliragon (4× MIC). Bacteria were cultured under control conditions or treated with azeliragon (4× MIC) or vancomycin (4× MIC), and viable counts (CFU/mL) were determined at indicated time points. Effects of azeliragon (4× MIC) on biofilm biomass of S. pneumoniae ATCC 49619 (D) , S. pneumoniae 1057 (E) , and S. pneumoniae 1044 (F) . Mature biofilms were treated with the indicated drugs for 24 h and quantified by crystal violet staining. Results are expressed as OD₅₇₀. Data were presented as mean ± SD. Data were presented as mean ± SD. The experiments were performed with six independent biological replicates ( n = 6). Group comparisons for biofilm assays were analyzed by one-way ANOVA followed by Tukey’s multiple-comparison test. “ns” represented no significant difference, *** p < 0.001.

Article Snippet: To further assess the effects of azeliragon on pneumococcal growth, the reference strain S. pneumoniae ATCC 49619 and two clinical isolates (1057 and 1044) were examined under different drug concentrations.

Techniques: Activity Assay, Disruption, Bacteria, Cell Culture, Control, Staining, Comparison

Journal: Frontiers in Medicine

Article Title: Protective effects of the RAGE inhibitor azeliragon as a potential anti- Streptococcus pneumoniae therapeutic in sepsis models

doi: 10.3389/fmed.2026.1793580

Figure Lengend Snippet: In vivo protective effects of azeliragon in a mouse infection model. (A) Determination of the infectious dose of S. pneumoniae 1044. (B) Therapeutic efficacy of azeliragon in the pneumonia model. (C) Seven-day survival curves of mice with sepsis induced by S. pneumoniae ATCC 49619. Mice received vehicle control, bacterial control, azeliragon (5 mg/kg or 10 mg/kg), or vancomycin (10 mg/kg). Each group contained 10 mice. Survival was monitored continuously. (D) Seven-day survival curves of mice with sepsis induced by the clinical S. pneumoniae isolate 1044. Experimental groups and treatments were identical to those in (A) . Survival data were plotted using the Kaplan–Meier method, and statistical significance was determined using the log-rank (Mantel–Cox) test. “ns” represented no significant difference, * p < 0.05, ** p < 0.01, and *** p < 0.001.

Article Snippet: To further assess the effects of azeliragon on pneumococcal growth, the reference strain S. pneumoniae ATCC 49619 and two clinical isolates (1057 and 1044) were examined under different drug concentrations.

Techniques: In Vivo, Infection, Drug discovery, Control