Intracellular proteome expression during 4-n-nonylphenol biodegradation by the filamentous fungus Metarhizium robertsii

4-n-nonylphenol (4-n-NP) is an endocrine disrupting compound (EDC); pollutants that cause serious disturbances in the environment. This study shows the degradation pathway and initial proteome analysis in cultures of a fungus that actively degrades 4-n-NP, Metarhizium robertsii. The research revealed the presence of 14 4-n-NP metabolites formed as a result of the oxidation of the alkyl chain and benzene ring, which leads to the complete decomposition of the compound. Based on the trend and quantitative analysis of the formation of 4-n-NP derivatives, the best conditions for proteome analysis were established. The data collected allowed the formulation of an explanation of the microorganism's strategy towards the removal of 4-n-NP. The main groups of proteins engaged in the removal of the xenobiotic are: oxidation-reduction systems related to nitroreductase-like proteins, ROS defense systems (peroxiredoxin and superoxide dismutase), the TCA cycle and energy-related systems. Principal components analysis was applied to unidentified proteins, resulting in the formulation of three subgroups and initial classification of these proteins

Proteome analysis of vernix caseosa

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldVernix caseosa (vernix) is a white creamy substance covering the skin of the fetus during the last trimester of pregnancy. The function of vernix has long been debated but no consensus has been reached. We here report a proteome analysis of vernix using two-dimensional gel electrophoresis, matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography coupled to tandem mass spectrometry. We have identified 41 proteins, of which 25 are novel to vernix. Notably, 39% of the identified vernix proteins are components of innate immunity, and 29% have direct antimicrobial properties. These results form a substantial contribution to the knowledge of vernix composition and demonstrate that antimicrobial protection of the fetus and the newborn child is a major and important function of vernix

Urinary proteomics using capillary electrophoresis coupled to mass spectrometry for diagnosis and prognosis in kidney diseases

Purpose of review: Urine is the most useful of body fluids for biomarker research. Therefore, we have focused on urinary proteomics, using capillary electrophoresis coupled to mass spectrometry, to investigate kidney diseases in recent years. Recent findings: Several urinary proteomics studies for the detection of various kidney diseases have indicated the potential of this approach aimed at diagnostic and prognostic assessment. Urinary protein biomarkers such as collagen fragments, serum albumin, [alpha]-1-antitrypsin, and uromodulin can help to explain the processes involved during disease progression. Summary: Urinary proteomics has been used in several studies in order to identify and validate biomarkers associated with different kidney diseases. These biomarkers, with improved sensitivity and specificity when compared with the current gold standards, provide a significant alternative for diagnosis and prognosis, as well as improving clinical decision-making

Salmonella Typhi, Paratyphi A, Enteritidis and Typhimurium core proteomes reveal differentially expressed proteins linked to the cell surface and pathogenicity

Background: Salmonella enterica subsp. enterica contains more than 2,600 serovars of which four are of major medical relevance for humans. While the typhoidal serovars (Typhi and Paratyphi A) are human-restricted and cause enteric fever, non-typhoidal Salmonella serovars (Typhimurium and Enteritidis) have a broad host range and predominantly cause gastroenteritis. Methodology/Principle findings: We compared the core proteomes of Salmonella Typhi, Paratyphi A, Typhimurium and Enteritidis using contemporary proteomics. For each serovar, five clinical isolates (covering different geographical origins) and one reference strain were grown in vitro to the exponential phase. Levels of orthologous proteins quantified in all four serovars and within the typhoidal and non-typhoidal groups were compared and subjected to gene ontology term enrichment and inferred regulatory interactions. Differential expression of the core proteomes of the typhoidal serovars appears mainly related to cell surface components and, for the non-typhoidal serovars, to pathogenicity. Conclusions/Significance: Our comparative proteome analysis indicated differences in the expression of surface proteins between Salmonella Typhi and Paratyphi A, and in pathogenesis-related proteins between Salmonella Typhimurium and Enteritidis. Our findings may guide future development of novel diagnostics and vaccines, as well as understanding of disease progression. Author summary: With an estimated 20 million typhoid cases and an even higher number of non-typhoid cases the health burden caused by salmonellosis is huge. Salmonellosis is caused by the bacterial species Salmonella enterica and over 2500 different serovars exist, of which four are of major medical relevance for humans: Typhi and Paratyphi A cause typhoid fever while Typhimurium and Enteritidis are the dominant cause of non-typhoidal Salmonella infections. The proteome is the entire set of proteins that is expressed by a genome and the core proteome are all orthologous proteins detected in a given sample set. In this study we have investigated differential expression of the core proteomes of the Salmonella serovars Typhi, Paratyphi A, Typhimurium and Enteritidis, as well as the regulating molecules. Our comparative proteome analysis indicated differences in the expression of surface proteins between the serovars Typhi and Paratyphi A, and in pathogenesis-related proteins between Typhimurium and Enteritidis. Our findings in proteome-wide expression may guide the development of novel diagnostics and vaccines for Salmonella, as well as understanding of disease

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study

Background Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis. Methods Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls. Results From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72–0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1)

Clinical proteomics for precision medicine: the bladder cancer case

Precision medicine can improve patient management by guiding therapeutic decision based on molecular characteristics. The concept has been extensively addressed through the application of –omics based approaches. Proteomics attract high interest, as proteins reflect a “real-time” dynamic molecular phenotype. Focusing on proteomics applications for personalized medicine, a literature search was conducted to cover: a) disease prevention, b) monitoring/ prediction of treatment response, c) stratification to guide intervention and d) identification of drug targets. The review indicates the potential of proteomics for personalized medicine by also highlighting multiple challenges to be addressed prior to actual implementation. In oncology, particularly bladder cancer, application of precision medicine appears especially promising. The high heterogeneity and recurrence rates together with the limited treatment options, suggests that earlier and more efficient intervention, continuous monitoring and the development of alternative therapies could be accomplished by applying proteomics-guided personalized approaches. This notion is backed by studies presenting biomarkers that are of value in patient stratification and prognosis, and by recent studies demonstrating the identification of promising therapeutic targets. Herein, we aim to present an approach whereby combining the knowledge on biomarkers and therapeutic targets in bladder cancer could serve as basis towards proteomics- guided personalized patient management

The use of urinary proteomics in the assessment of suitability of mouse models for ageing

Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8–96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing