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Microarray analysis of toxicogenomic effects of ortho-phenylphenol in Staphylococcus aureus
Hyeung-Jin Jang1, Chantal Nde, Freshteh Toghrol
1Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA. jang.hyeungjin@epa.gov
Background:
Staphylococcus aureus (S. aureus), is responsible for many infectious diseases, ranging from benign skin infections to life-threatening endocarditis and toxic shock syndrome. Ortho-phenylphenol (OPP) is an antimicrobial agent and an active ingredient of EPA-registered disinfectants with wide human exposure in various agricultural, hospital and veterinary disinfectant products. Despite many uses, an understanding of a cellular response to OPP and it's mechanism of action, targeted genes, and the connectivity between targeted genes and the rest of cell metabolism remains obscure.
Results:
Herein, we performed a genome-wide transcriptome analysis of the cellular responses of S. aureus when exposed to 0.82 mM of OPP for 20 and 60 min. Our data indicated that OPP downregulated the biosynthesis of many amino acids, which are required for protein synthesis. In particular, the genes encoding the enzymes of the diaminopimelate (DAP) pathway which results in lysine biosynthesis were significantly downregualted. Intriguingly, we revealed that the transcription of genes encoding ribosomal proteins was upregulated by OPP and at the same time, the genes encoding iron acquisition and transport were downregulated. The genes encoding virulence factors were upregulated and genes encoding phospholipids were downregulated upon 20 min exposure to OPP.
Conclusion:
By using microarray analysis that enables us to simultaneously and globally examine the complete transcriptome during cellular responses, we have revealed novel information regarding the mode of action of OPP on Staphylococcus: OPP inhibits anabolism of many amino acids and highly downregulates the genes that encode the enzymes involved in the DAP pathway. Lysine and DAP are essential for building up the peptidoglycan cell wall. It was concluded that the mode of action of OPP is similar to the mechanism of action of some antibiotics. The discovery of this phenomenon provides useful information that will benefit further antimicrobial research on S. aureus.
Insights
Ortho-phenylphenol (OPP) disrupts Staphylococcus aureus cell metabolism by downregulating amino acid synthesis, particularly the diaminopimelate (DAP) pathway essential for cell wall formation. This antimicrobial action offers insights for developing new S. aureus therapies.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Staphylococcus aureus causes diverse infections, from skin issues to severe systemic diseases.
- Ortho-phenylphenol (OPP) is a widely used antimicrobial in disinfectants, but its cellular mechanisms are unclear.
Purpose of the Study:
- To elucidate the cellular response and gene expression changes in S. aureus upon exposure to OPP.
- To identify the specific genes and metabolic pathways targeted by OPP.
Main Methods:
- Genome-wide transcriptome analysis using microarray technology.
- Exposure of S. aureus to 0.82 mM OPP for 20 and 60 minutes.
Main Results:
- OPP significantly downregulated amino acid biosynthesis, especially the diaminopimelate (DAP) pathway crucial for lysine production.
- Genes for ribosomal proteins were upregulated, while those for iron acquisition and phospholipids were downregulated.
- Virulence factor genes were upregulated after 20 minutes of OPP exposure.
Conclusions:
- OPP inhibits amino acid anabolism and strongly downregulates DAP pathway enzymes, impacting peptidoglycan synthesis.
- The mode of action of OPP resembles that of certain antibiotics, providing valuable data for antimicrobial research.
- Understanding OPP's effects aids in developing novel strategies against S. aureus infections.
