Azithromycin Inhibits Biofilm Formation by Staphylococcus xylosus and Affects Histidine Biosynthesis Pathway

Abstract

Staphylococcus xylosus, a coagulase-negative, non-pathogenic bacterium, responsible for opportunistic infections in humans and bovine mastitis, has the ability to form biofilms, which are responsible for persistent infections and antibiotic resistance. In our study, azithromycin significantly inhibited biofilm formation by altering protein expression. Of the 1764 proteins measured by the isobaric Tag for Relative and Absolute Quantification (iTRAQ) technique, only 148 proteins showed significantly different expression between the azithromycin-treated and untreated cells. Most ribosomal proteins were markedly up-regulated, and the expression of the proteins involved in histidine biosynthesis, which, in turn, influence biofilm formation, was down-regulated, particularly imidazole glycerophosphate dehydratase (IGPD). Previously, we had observed that IGPD plays an important role in biofilm formation by S. xylosus. Therefore, hisB expression was studied by real-time PCR, and the interactions between azithromycin and IGPD were predicted by molecular docking analysis. hisB was found to be significantly down-regulated, and six bond interactions were observed between azithromycin and IGPD. Many active atoms of azithromycin did not interact with the biologically active site of IGPD. Surface plasmon resonance analysis used to further study the relationship between IGPD and azithromycin showed minimum interaction between them. Histidine content in the azithromycin-treated and untreated groups was determined. We noted a slight difference, which was not consistent with the expression of the proteins involved in histidine biosynthesis. Therefore, histidine degradation into glutamate was also studied, and we found that all proteins were down-regulated. This could be the reason why histidine content showed little change between the treated and untreated groups. In summary, we found that azithromycin is a potential inhibitor of S. xylosus biofilm formation, and the underlying mechanism was preliminarily elucidated in this study.

Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome

“…The connection between these lifestyle conditions and histidine metabolism has not been studied in B. subtilis , but it has been observed in A. baumannii , where histidine degradation was shown to be upregulated in proteomic studies of biofilms, and histidine supplementation stimulated increased biofilm production 37 . Two recent studies discovered that biofilm-inhibiting antimicrobials worked by suppressing histidine synthesis in Staphylococcus xylosus 38 , 39 . One proposed mechanism implicated the production of extracellular DNA, which is an important component of both A. baumannii and B. subtilis biofilms 40 .…”

Rhein against Staphylococcus xylosus by interfering with respiratory metabolism and inducing oxidative stress

“…Gene Ontology (GO) serves as a crucial bioinformatics analysis method and tool for expressing various properties of genes and their products ( Milano, 2022 ). GO annotations are categorized into three groups: Biological Process, Molecular Function, and Cellular Component, providing insights into the biological roles of proteins from different perspectives ( Ding et al, 2018 ). The differential proteins obtained from the experiments underwent GO enrichment analysis, with the results depicted in Fig.…”

Effect of Selected Antibiotics on Biofilm Formed by <i>Salmonella Enterica</i> Serovars Typhi and Paratyphi

“…A previous report indicated that Azithromycin was effective at sub-MIC levels against Porphyromonas gingivalis biofilms and could be used for future clinical treatment for oral biofilm infections 17 which is similar to our finding. Similarly, Azithromycin is also a potential inhibitor of Staphylococcus xylosus biofilm formation by altering protein expression 18 .…”