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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) upon 20 min and 60 min exposures (a total of 431 genes). Note that the functional classes of "hypothetical genes", "general function prediction only" and "function unknown" are not included in this figure.
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Figure 4: Functional classification of genes with statistically significant upregulated (red) and downregulated (green) upon 20 min and 60 min exposures (a total of 431 genes). Note that the functional classes of "hypothetical genes", "general function prediction only" and "function unknown" are not included in this figure.

Mentions: To further identify genes with similar transcription patterns during the time course, we removed 238 genes (including the group of functional unknown (36), hypothetical protein (132) and general function predicted only (70)). We categorized 431 genes with known functions into 6 groups on the basis of their transcription directions (figure 3). Briefly, group I contained 23 genes upregulated upon both exposure times, while group II had 80 genes with increased expression levels at 20 min and no significant changes upon 60 min exposure. Further, group III possessed 26 genes that were upregulated at 60 min exposure. Group IV contained 128 genes downregulated upon both exposure times, whereas 95 genes of group V exhibited downregulation after 20 min. Finally, group VI had 79 genes that were downregulated upon 60 min exposure. Figure 4 displays the number of genes (431) within groups I through VI in each functional class. As indicated above, additional file 2 contains all 669 genes including the genes classified under the functional group designated as "unknown, hypothetical, and general function prediction only".


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) upon 20 min and 60 min exposures (a total of 431 genes). Note that the functional classes of "hypothetical genes", "general function prediction only" and "function unknown" are not included in this figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Functional classification of genes with statistically significant upregulated (red) and downregulated (green) upon 20 min and 60 min exposures (a total of 431 genes). Note that the functional classes of "hypothetical genes", "general function prediction only" and "function unknown" are not included in this figure.
Mentions: To further identify genes with similar transcription patterns during the time course, we removed 238 genes (including the group of functional unknown (36), hypothetical protein (132) and general function predicted only (70)). We categorized 431 genes with known functions into 6 groups on the basis of their transcription directions (figure 3). Briefly, group I contained 23 genes upregulated upon both exposure times, while group II had 80 genes with increased expression levels at 20 min and no significant changes upon 60 min exposure. Further, group III possessed 26 genes that were upregulated at 60 min exposure. Group IV contained 128 genes downregulated upon both exposure times, whereas 95 genes of group V exhibited downregulation after 20 min. Finally, group VI had 79 genes that were downregulated upon 60 min exposure. Figure 4 displays the number of genes (431) within groups I through VI in each functional class. As indicated above, additional file 2 contains all 669 genes including the genes classified under the functional group designated as "unknown, hypothetical, and general function prediction only".

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