Methicillin-Resistant Staphylococcus aureus Proteome Response to Antibiotic Stress Provides Insights for New Therapeutic Strategies.
Miguel RibeiroSara CeballosPatrícia PoetaCarmen TorresGilberto IgrejasPublished in: Omics : a journal of integrative biology (2021)
Antimicrobial resistance is a global threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the most representative drug-resistant pathogens. MRSA spread is increasing due to its ability to establish new reservoirs. To this end, the clonal complex (CC)-130 is an emerging genetic lineage, generally regarded as animal adapted and carrying the mecC gene, and sporadically found in humans. Although the MRSA antibiotic resistance mechanisms have been described, there are limited data on systems-wide omics responses to antibiotic stress, particularly at the proteome level. In this study, a gel-based quantitative proteomics approach was performed to assess the cellular responses of a mecC-harboring CC130 MRSA strain of human origin to subinhibitory doses of cefoxitin. We focused on the global response of MRSA to antibiotic stress and upon this treatment, 53 proteins were significantly differentially expressed. Most of the latter proteins were mapped to having functions in cellular metabolism while some glycolysis-related proteins showed a decreased expression after cefoxitin stress. On the contrary, pyruvate kinase, a potential antimicrobial drug target, was found upregulated. Also, quorum sensing, genetic information processing, and stress response proteins were found upregulated. Low-affinity penicillin-binding protein (mecC-encoded) was found in cefoxitin-treated samples. In conclusion, these new findings on cefoxitin-induced proteome changes provide important insights and molecular leads for innovation in treatment of MRSA specifically, and omics approaches to address antibiotic resistance generally.
Keyphrases
- methicillin resistant staphylococcus aureus
- staphylococcus aureus
- drug resistant
- antimicrobial resistance
- binding protein
- multidrug resistant
- genome wide
- single cell
- stress induced
- endothelial cells
- emergency department
- dna methylation
- gene expression
- drug induced
- high glucose
- heat stress
- cystic fibrosis
- tyrosine kinase
- gram negative
- cross sectional
- machine learning
- big data
- oxidative stress
- artificial intelligence
- human health
- adverse drug
- health information
- newly diagnosed