Toxicogenomic response of Pseudomonas aeruginosa to ortho-phenylphenol.
BACKGROUND
Pseudomonas aeruginosa (P. aeruginosa) is the most common opportunistic pathogen implicated in nosocomial infections and in chronic lung infections in cystic fibrosis patients. Ortho-phenylphenol (OPP) is an antimicrobial agent used as an active ingredient in several EPA registered disinfectants. Despite its widespread use, there is a paucity of information on its target molecular pathways and the cellular responses that it elucidates in bacteria in general and in P. aeruginosa in particular. An understanding of the OPP-driven gene regulation and cellular response it elicits will facilitate more effective utilization of this antimicrobial and possibly lead to the development of more effective disinfectant treatments.


RESULTS
Herein, we performed a genome-wide transcriptome analysis of the cellular responses of P. aeruginosa exposed to 0.82 mM OPP for 20 and 60 minutes. Our data indicated that OPP upregulated the transcription of genes encoding ribosomal, virulence and membrane transport proteins after both treatment times. After 20 minutes of exposure to 0.82 mM OPP, genes involved in the exhibition of swarming motility and anaerobic respiration were upregulated. After 60 minutes of OPP treatment, the transcription of genes involved in amino acid and lipopolysaccharide biosynthesis were upregulated. Further, the transcription of the ribosome modulation factor (rmf) and an alternative sigma factor (rpoS) of RNA polymerase were downregulated after both treatment times.


CONCLUSIONS
Results from this study indicate that after 20 minutes of exposure to OPP, genes that have been linked to the exhibition of anaerobic respiration and swarming motility were upregulated. This study also suggests that the downregulation of the rmf and rpoS genes may be indicative of the mechanism by which OPP causes decreases in cell viability in P. aeruginosa. Consequently, a protective response involving the upregulation of translation leading to the increased synthesis of membrane related proteins and virulence proteins is possibly induced after both treatment times. In addition, cell wall modification may occur due to the increased synthesis of lipopolysaccharide after 60 minutes exposure to OPP. This gene expression profile can now be utilized for a better understanding of the target cellular pathways of OPP in P. aeruginosa and how this organism develops resistance to OPP.
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA. nde.chantal@epa.gov
Chantal W
CW
Nde
Hyeung-Jin
HJ
Jang
Freshteh
F
Toghrol
William E
WE
Bentley
D001713:Biphenyl Compounds / Q000494:pharmacology*; D003428:Cross Infection / Q000517:prevention & control; D004202:Disinfectants / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009894:Opportunistic Infections / Q000517:prevention & control; D011552:Pseudomonas Infections / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D001713:Biphenyl Compounds; D004202:Disinfectants; D012329:RNA, Bacterial; C004369:2-phenylphenol