Microarray analysis of toxicogenomic effects of ortho-phenylphenol in Staphylococcus aureus.
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.


CONCLUSIONS
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.
Jang
Hyeung-Jin
HJ
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA. jang.hyeungjin@epa.gov
Nde
Chantal
C
Toghrol
Freshteh
F
Bentley
William E
WE
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D023281:Genomics; D008239:Lysine / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism
D000890:Anti-Infective Agents; D001713:Biphenyl Compounds; C004369:2-phenylphenol; D008239:Lysine
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