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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

S. aureus growth (optical density at 600 nm) after treatment with OPP: control (open triangles), with DMSO (closed triangles), 0.71 mM (inverted closed triangles), 0.82 mM (closed circles), 0.94 mM (open squares), and 1.18 mM OPP (X). Growth inhibition was performed during the exponential phase of the cells without DMSO (control) and control with DMSO, 0.71 mM, 0.82 mM, 0.94 mM, and 1.18 mM OPP dissolved in DMSO. The results are the mean of triplicate experiments; the error bars represent standard deviation.
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Figure 1: S. aureus growth (optical density at 600 nm) after treatment with OPP: control (open triangles), with DMSO (closed triangles), 0.71 mM (inverted closed triangles), 0.82 mM (closed circles), 0.94 mM (open squares), and 1.18 mM OPP (X). Growth inhibition was performed during the exponential phase of the cells without DMSO (control) and control with DMSO, 0.71 mM, 0.82 mM, 0.94 mM, and 1.18 mM OPP dissolved in DMSO. The results are the mean of triplicate experiments; the error bars represent standard deviation.

Mentions: To determine the sublethal inhibitory effect of OPP on S. aureus, we first exposed the exponentially growing cells to different concentrations of OPP dissolved in DMSO (0 up to 1.18 mM). In figure 1, we demonstrate that 0.82 mM concentration of OPP caused a growth inhibition for about 20 min. Note that minimum inhibitory concentration (MIC50) of OPP on S. aureus was reportedly 500 mg/l (3 mM) [16]. In this study, to better understand how S. aureus initially responds to OPP, we chose the rate of cell growth inhibition with 0.82 mM OPP after 20 and 60 min exposure times compared to control (without OPP).


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

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

S. aureus growth (optical density at 600 nm) after treatment with OPP: control (open triangles), with DMSO (closed triangles), 0.71 mM (inverted closed triangles), 0.82 mM (closed circles), 0.94 mM (open squares), and 1.18 mM OPP (X). Growth inhibition was performed during the exponential phase of the cells without DMSO (control) and control with DMSO, 0.71 mM, 0.82 mM, 0.94 mM, and 1.18 mM OPP dissolved in DMSO. The results are the mean of triplicate experiments; the error bars represent standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: S. aureus growth (optical density at 600 nm) after treatment with OPP: control (open triangles), with DMSO (closed triangles), 0.71 mM (inverted closed triangles), 0.82 mM (closed circles), 0.94 mM (open squares), and 1.18 mM OPP (X). Growth inhibition was performed during the exponential phase of the cells without DMSO (control) and control with DMSO, 0.71 mM, 0.82 mM, 0.94 mM, and 1.18 mM OPP dissolved in DMSO. The results are the mean of triplicate experiments; the error bars represent standard deviation.
Mentions: To determine the sublethal inhibitory effect of OPP on S. aureus, we first exposed the exponentially growing cells to different concentrations of OPP dissolved in DMSO (0 up to 1.18 mM). In figure 1, we demonstrate that 0.82 mM concentration of OPP caused a growth inhibition for about 20 min. Note that minimum inhibitory concentration (MIC50) of OPP on S. aureus was reportedly 500 mg/l (3 mM) [16]. In this study, to better understand how S. aureus initially responds to OPP, we chose the rate of cell growth inhibition with 0.82 mM OPP after 20 and 60 min exposure times compared to control (without 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