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

Jang HJ, Nde C, Toghrol F, Bentley WE - BMC Genomics (2008)

Bottom Line: In particular, the genes encoding the enzymes of the diaminopimelate (DAP) pathway which results in lysine biosynthesis were significantly downregualted.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA. jang.hyeungjin@epa.gov

ABSTRACT

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.

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Related in: MedlinePlus

Functional classification of genes with statistically significant upregulated (red) and downregulated (green) when exposed to 0.82 mM OPP at 20 min and 60 min (a total of 669 genes). The number in parenthesis represents the total number of genes affected within the genome in each functional class.
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Figure 2: Functional classification of genes with statistically significant upregulated (red) and downregulated (green) when exposed to 0.82 mM OPP at 20 min and 60 min (a total of 669 genes). The number in parenthesis represents the total number of genes affected within the genome in each functional class.

Mentions: In Figure 2, the differences between the numbers of up and downregulated genes in each functional class after 20 and 60 minutes exposure to 0.82 mM of OPP are illustrated. Note that Figure 2 represents a total of 669 genes including the group of "function unknown (36), hypothetical protein (132) and general function predicted only (70)". Some interesting findings are as follows: (i) the genes of amino acid transport and metabolism were highly downregulated at both 20 and 60 min; (ii) the genes of inorganic ion transport and metabolism were downregulated at 20 min and decrease in the number of genes downregulated at 60 min was also observed; (iii) the genes in the class of "translation, ribosomal structure and biogenesis" were significantly upregulated at 20 min; (iv) the number of genes involved in nucleotide transport and metabolism were increased after 20 min compared to after 60 min. In general, figure 2 illustrates that the functional classes contained more downregulated and fewer upregulated genes at 20 min. This result suggests that the functional class profiles were notably different between 20 and 60 min, and this difference might explain why S. aureus underwent the initial growth inhibition followed by partial growth recovery upon exposure to OPP.


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

Jang HJ, Nde C, Toghrol F, Bentley WE - BMC Genomics (2008)

Functional classification of genes with statistically significant upregulated (red) and downregulated (green) when exposed to 0.82 mM OPP at 20 min and 60 min (a total of 669 genes). The number in parenthesis represents the total number of genes affected within the genome in each functional class.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2562396&req=5

Figure 2: Functional classification of genes with statistically significant upregulated (red) and downregulated (green) when exposed to 0.82 mM OPP at 20 min and 60 min (a total of 669 genes). The number in parenthesis represents the total number of genes affected within the genome in each functional class.
Mentions: In Figure 2, the differences between the numbers of up and downregulated genes in each functional class after 20 and 60 minutes exposure to 0.82 mM of OPP are illustrated. Note that Figure 2 represents a total of 669 genes including the group of "function unknown (36), hypothetical protein (132) and general function predicted only (70)". Some interesting findings are as follows: (i) the genes of amino acid transport and metabolism were highly downregulated at both 20 and 60 min; (ii) the genes of inorganic ion transport and metabolism were downregulated at 20 min and decrease in the number of genes downregulated at 60 min was also observed; (iii) the genes in the class of "translation, ribosomal structure and biogenesis" were significantly upregulated at 20 min; (iv) the number of genes involved in nucleotide transport and metabolism were increased after 20 min compared to after 60 min. In general, figure 2 illustrates that the functional classes contained more downregulated and fewer upregulated genes at 20 min. This result suggests that the functional class profiles were notably different between 20 and 60 min, and this difference might explain why S. aureus underwent the initial growth inhibition followed by partial growth recovery upon exposure to OPP.

Bottom Line: In particular, the genes encoding the enzymes of the diaminopimelate (DAP) pathway which results in lysine biosynthesis were significantly downregualted.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA. jang.hyeungjin@epa.gov

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus