Comparative Proteomic Analysis Provides insight into the Key Proteins as Possible Targets Involved in Aspirin Inhibiting Biofilm Formation of Staphylococcus xylosus

Abstract

Staphylococcus xylosus is an opportunistic pathogen that causes infection in humans and cow mastitis. And S. xylosus possesses a strong ability to form biofilms in vitro. As biofilm formation facilitates resistance to antimicrobial agents, the discovery of new medicinal properties for classic drugs is highly desired. Aspirin, which is the most common active component of non-steroidal anti-inflammatory compounds, affects the biofilm-forming capacity of various bacterial species. We have found that aspirin effectively inhibits biofilm formation of S. xylosus by Crystal violet (CV) staining and scanning electron microscopy analyses. The present study sought to elucidate possible targets of aspirin in suppressing S. xylosus biofilm formation. Based on an isobaric tag for relative and absolute quantitation (iTRAQ) fold-change of >1.2 or <0.8 (P-value < 0.05), 178 differentially expressed proteins, 111 down-regulated and 67 up-regulated, were identified after application of aspirin to cells at a 1/2 minimal inhibitory concentration. Gene ontology analysis indicated enrichment in metabolic processes for the majority of the differentially expressed proteins. We then used the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database to analyze a large number of differentially expressed proteins and identified genes involved in biosynthesis of amino acids pathway, carbon metabolism (pentose phosphate and glycolytic pathways, tricarboxylic acid cycle) and nitrogen metabolism (histidine metabolism). These novel proteins represent candidate targets in aspirin-mediated inhibition of S. xylosus biofilm formation at sub-MIC levels. The findings lay the foundation for further studies to identify potential aspirin targets.

An Integrated Lipidomics and Phenotype Study Reveals Protective Effect and Biochemical Mechanism of Traditionally Used Alisma orientale Juzepzuk in Chronic Kidney Disease

“…In order to construct a metabolic network of identified lipids, we integrated interaction databases: Reactome, Database for Annotation, Visualization and Integrated Discovery (DAVID), Kyoto Encyclopedia of Genes and Genomes (KEGG), Biomolecular Interaction Network Database (BIND), Human Protein Reference Database (HPRD), BioGrid, Database of Interacting Proteins (DIP), Metabolite Set Enrichment Analysis (MSEA), and Quantitative Enrichment Analysis (QEA) (Xenarios et al, 2002 ; Bader et al, 2003 ; Huang da et al, 2009 ; Goel et al, 2012 ; Xu et al, 2017 ). These databases contained the most comprehensive publicly available repository of genes, proteins, and interaction of complexes for Homo sapiens.…”

Homology Modeling and Virtual Screening to Discover Potent Inhibitors Targeting the Imidazole Glycerophosphate Dehydratase Protein in Staphylococcus xylosus

“…It is pivotal to construct the 3D IGPD structure based on the known structures by homology modeling method. The amino acid sequences of the IGPD protein were isobarically tagged for relative and absolute quantitation (iTRAQ) labeling (Xu et al, 2017 ; Table 1 ). Hence, sequence similarity searches were carried out by utilizing BLASTp analysis (Altschul et al, 1990 ), which revealed suitable templates for the homology modeling.…”

“…S. xylosus is also one of the coagulase-negative staphylococci (CoNS) (Osman et al, 2016 ), which has strong ability of biofilm formation (Planchon et al, 2006 , 2009 ). In addition, the L-histidine synthesis pathway is involved in the formation of biofilm in S. xylosus (Xu et al, 2017 ). The imidazole glycerophosphate dehydratase (IGPD), one of the specific enzymes, catalyzes the dehydration of imidazoleglycerol phosphate (IGP) to imidazoleacetol phosphate (IAP) (Hawkes et al, 1995 ), which synthesize L-histidine in the synthesis pathway (Dietl et al, 2016 ).…”

Transporters and Efflux Pumps Are the Main Mechanisms Involved in Staphylococcus epidermidis Adaptation and Tolerance to Didecyldimethylammonium Chloride

“…Other genes involved in amino-acid biosynthetic pathways were down-regulated, including (SE0275, -7-fold); this gene encodes 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino) methylideneamino] imidazole-4-carboxamide isomerase, which is involved in L-histidine biosynthesis. Down-regulation of hisA was also seen for Staphylococcus xylosus after exposure to aspirin [60]. Ketol-acid reductoisomerase (SE1657, -8.1-fold) is involved in branched-chain amino-acid biosynthesis [61].…”