14 research outputs found
Citrobacter youngae nosocomial bacteremia from postoperative pyogenic spondylodiscitis after a minimally invasive spinal surgery
No full textAbstract Citrobacter youngae (C. youngae) was first described in 1993, and data suggesting that human diseases caused by this bacterium remain scarce. Reports on C. youngae infections mostly described local infections without evidenced bacteremia, especially in immunocompromised patients. Herein, we report a rare case of bacteremia with intervertebral disc and adjacent vertebral infection due to C. youngae (detected by the Vitek® 2 Compact). A 70-year-old man with chronic lower back pain due to lumbar disc herniation underwent microdiscectomy, a minimally invasive spinal surgery. On postoperative day 4, he suffered shaking chills with worsened lower back pain compared to that before the operation, and vancomycin plus ceftriaxone were empirically administered. Magnetic resonance imaging (MRI) of the lumbar spine revealed osteomyelitis at L4 and L5 with L4/L5 discitis. Two blood culture sets were positive with the same pathogen, possibly C. youngae; The patient was then treated successfully with ceftazidime plus ciprofloxacin, the antibiotics were selected based on antibiotic susceptibility test results. This report suggests that C. youngae may cause severe infections in immunocompetent patients, and further surveillance should be considered to monitor antibiotic-resistant bacteria
A novel micronemal protein MP38 is involved in the invasion of merozoites into erythrocytes.
No full textThe absence of an in vitro cultivation system for Plasmodium vivax hinders the exploration of molecular targets for vaccine development. To address this, functional studies often rely on alternative models, such as P. knowlesi, due to its genetic similarity to P. vivax. This study investigated the role of a novel micronemal protein, PvMP38 (PVX_110945), in both P. vivax and P. knowlesi merozoite invasion of erythrocytes. The full-length ectodomain of PvMP38 was expressed, and polyclonal antibodies were generated to assess its function. PvMP38 was confirmed to localize on micronemal organelle in both P. vivax and P. knowlesi merozoites. In vitro protein-protein interaction assays revealed that PvMP38 binds to Pv12 with high-affinity interaction. A conserved novel complex of Pv12-Pv41-PvMP38 was identified by immunoprecipitation of P. vivax antibodies on P. knowlesi schizont lysates. Linear epitopes of PvMP38 with high and moderate antigenicity were identified in clinical isolates of both species. Invasion inhibition assays demonstrated that a triple antibody combination targeting the PvMP38, Pv12, and Pv41 significantly reduced P. knowlesi merozoite invasion of erythrocytes compared to a single antibody. In addition, CRISPR/Cas9-mediated knockout of P. knowlesi mp38 markedly impaired parasite growth, underscoring its essential role during the asexual stage. These findings identify PvMP38 and its associated complex as promising targets for malaria interventions and highlight the utility of P. knowlesi as a model for investigating P. vivax erythrocyte invasion mechanisms.IMPORTANCEThis manuscript reported an effort in malaria eradication by identifying and functionally characterizing a novel Plasmodium vivax micronemal protein, PvMP38, involved in erythrocyte invasion. A narrow repertoire of an efficacious vaccine targeting P. vivax candidates is being developed due to the lack of continuous in vitro culture. This study addresses a gap in P. vivax research using P. knowlesi as a model for both genome editing and antibody functionality validation. By enhancing the protein-protein interaction screening framework, this study demonstrated that PvMP38 forms a complex with Pv12 and Pv41, opening the approaches to multi-antigen vaccines. The successful application of CRISPR/Cas9 gene editing techniques to disrupt its homolog, the pkmp38 gene, further assesses the protein's significance in the growth and invasion of the parasite. These findings provided valuable insights into the biology of P. vivax and proposed PvMP38 as a promising candidate for malaria intervention strategies
Circulating miR-147b as a diagnostic marker for patients with bacterial sepsis and septic shock.
No full textBackgroundEarly diagnosis, precise antimicrobial treatment and subsequent patient stratification can improve sepsis outcomes. Circulating biomarkers such as plasma microRNAs (miRNAs) have proven to be surrogates for diagnosis, severity and case management of infections. The expression of four selected miRNAs (miR-146-3p, miR-147b, miR-155 and miR-223) was validated for their prognostic and diagnostic potential in a clinically defined cohort of patients with sepsis and septic shock.MethodsThe expression of plasma miRNAs was quantified by quantitative PCR (qPCR) in patients with bacterial sepsis (n = 78), in patients with septic shock (n = 52) and in patients with dengue haemorrhagic fever (DHF; n = 69) and in healthy controls (n = 82).ResultsThe expression of studied miRNA was significantly increased in patients with bacterial sepsis and septic shock. The plasma miR-147b was able to differentiate bacterial sepsis from non-sepsis and septic shock (AUC = 0.77 and 0.8, respectively, p≤ 0.05), while the combination of plasma miR-147b and procalcitonin (PCT) predicted septic shock (AUC = 0.86, p≤ 0.05).ConclusionsThe plasma miR-147b may be an useful biomarker independently or in combination with PCT to support clinical diagnosis of sepsis and equally prognosis of patients with septic shock
Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites
No full textPlasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria
DataSheet_1_Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites.docx
No full textPlasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.</p
Additional file 1 of Plasmodium vivax merozoite-specific thrombospondin-related anonymous protein (PvMTRAP) interacts with human CD36, suggesting a novel ligand–receptor interaction for reticulocyte invasion
No full textAdditional file 1: Figure S1. (A) SDS‒PAGE analysis of 13 recombinant proteins that are abundant on reticulocytes and were expressed and purified based on the Fc-tag. Different migration of protein under reducing (R) and non-reducing (N) conditions confirmed the existence of the Fc-tag. (B) Quality assessment of PvDBP-RII using ELISA and BLI experiments
The value of miRNA and PCT in differentiating diagnostics sepsis and non-sepsis and/or sepsis shock.
No full textThe value of miRNA and PCT in differentiating diagnostics sepsis and non-sepsis and/or sepsis shock.</p
Characteristics of study participants according to clinical presentation.
No full textCharacteristics of study participants according to clinical presentation.</p
High expression of selected microRNAs is associated with septic shock.
No full textRelative expression of individual miRNA (miR-146-3p, miR-147b, miR-155 and miR-223) in sepsis patients with and without shock. P values were calculated by Wilcoxon tests.</p
Combination of miR-147b and serological PCT can predict septic shock.
No full textDiagnostic performance of the models built based on random forest models with single or double combination of miRNAs or double combination of individual miRNA and PCT in differentiating septic shock patients from non-septic shock patients.</p
