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A putative de-N-acetylase of the PIG-L superfamily affects fluoroquinolone tolerance in Pseudomonas aeruginosa

(2014) PATHOGENS AND DISEASE. 71(1). p.39-54
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Bioinformatics: from nucleotids to networks (N2N)
Abstract
A major cause of treatment failure of infections caused by Pseudomonas aeruginosa is the presence of antibiotic-insensitive persister cells. The mechanism of persister formation in P.aeruginosa is largely unknown, and so far, only few genetic determinants have been linked to P.aeruginosa persistence. Based on a previous high-throughput screening, we here present dnpA (de-N-acetylase involved in persistence; gene locus PA14_66140/PA5002) as a new gene involved in noninherited fluoroquinolone tolerance in P.aeruginosa. Fluoroquinolone tolerance of a dnpA mutant is strongly reduced both in planktonic culture and in a biofilm model, whereas overexpression of dnpA in the wild-type strain increases the persister fraction. In addition, the susceptibility of the dnpA mutant to different classes of antibiotics is not affected. dnpA is part of the conserved LPS core oligosaccharide biosynthesis gene cluster. Based on primary sequence analysis, we predict that DnpA is a de-N-acetylase, acting on an unidentified substrate. Site-directed mutagenesis suggests that this enzymatic activity is essential for DnpA-mediated persistence. A transcriptome analysis indicates that DnpA primarily affects the expression of genes involved in surface-associated processes. We discuss the implications of these findings for future antipersister therapies targeted at chronic P.aeruginosa infections.
Keywords
PERSISTER CELLS, IBCN, persistence, phenotypic tolerance, LPS, LmbE, BACTERIAL PERSISTENCE, SUBSTRATE-SPECIFICITY, GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS, ENTAMOEBA-HISTOLYTICA, ANTIBIOTIC TOLERANCE, GENETIC-DETERMINANTS, ESCHERICHIA-COLI, POLYACRYLAMIDE-GELS, ANCHOR BIOSYNTHESIS

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Citation

Please use this url to cite or link to this publication:

Chicago
Liebens, Veerle, Valerie Defraine, Annelies Van der Leyden, Valerie N De Groote, Carolina Fierro, Serge Beullens, Natalie Verstraeten, et al. 2014. “A Putative de-N-acetylase of the PIG-L Superfamily Affects Fluoroquinolone Tolerance in Pseudomonas Aeruginosa.” Pathogens and Disease 71 (1): 39–54.
APA
Liebens, V., Defraine, V., Van der Leyden, A., De Groote, V. N., Fierro, C., Beullens, S., Verstraeten, N., et al. (2014). A putative de-N-acetylase of the PIG-L superfamily affects fluoroquinolone tolerance in Pseudomonas aeruginosa. PATHOGENS AND DISEASE, 71(1), 39–54.
Vancouver
1.
Liebens V, Defraine V, Van der Leyden A, De Groote VN, Fierro C, Beullens S, et al. A putative de-N-acetylase of the PIG-L superfamily affects fluoroquinolone tolerance in Pseudomonas aeruginosa. PATHOGENS AND DISEASE. 2014;71(1):39–54.
MLA
Liebens, Veerle, Valerie Defraine, Annelies Van der Leyden, et al. “A Putative de-N-acetylase of the PIG-L Superfamily Affects Fluoroquinolone Tolerance in Pseudomonas Aeruginosa.” PATHOGENS AND DISEASE 71.1 (2014): 39–54. Print.
@article{5663423,
  abstract     = {A major cause of treatment failure of infections caused by Pseudomonas aeruginosa is the presence of antibiotic-insensitive persister cells. The mechanism of persister formation in P.aeruginosa is largely unknown, and so far, only few genetic determinants have been linked to P.aeruginosa persistence. Based on a previous high-throughput screening, we here present dnpA (de-N-acetylase involved in persistence; gene locus PA14\_66140/PA5002) as a new gene involved in noninherited fluoroquinolone tolerance in P.aeruginosa. Fluoroquinolone tolerance of a dnpA mutant is strongly reduced both in planktonic culture and in a biofilm model, whereas overexpression of dnpA in the wild-type strain increases the persister fraction. In addition, the susceptibility of the dnpA mutant to different classes of antibiotics is not affected. dnpA is part of the conserved LPS core oligosaccharide biosynthesis gene cluster. Based on primary sequence analysis, we predict that DnpA is a de-N-acetylase, acting on an unidentified substrate. Site-directed mutagenesis suggests that this enzymatic activity is essential for DnpA-mediated persistence. A transcriptome analysis indicates that DnpA primarily affects the expression of genes involved in surface-associated processes. We discuss the implications of these findings for future antipersister therapies targeted at chronic P.aeruginosa infections.},
  author       = {Liebens, Veerle and Defraine, Valerie and Van der Leyden, Annelies and De Groote, Valerie N and Fierro, Carolina and Beullens, Serge and Verstraeten, Natalie and Kint, Cyrielle and Jans, Ann and Frangipani, Emanuela and Visca, Paolo and Marchal, Kathleen and Vers{\'e}es, Wim and Fauvart, Maarten and Michiels, Jan},
  issn         = {2049-632X},
  journal      = {PATHOGENS AND DISEASE},
  keyword      = {PERSISTER CELLS,IBCN,persistence,phenotypic tolerance,LPS,LmbE,BACTERIAL PERSISTENCE,SUBSTRATE-SPECIFICITY,GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS,ENTAMOEBA-HISTOLYTICA,ANTIBIOTIC TOLERANCE,GENETIC-DETERMINANTS,ESCHERICHIA-COLI,POLYACRYLAMIDE-GELS,ANCHOR BIOSYNTHESIS},
  language     = {eng},
  number       = {1},
  pages        = {39--54},
  title        = {A putative de-N-acetylase of the PIG-L superfamily affects fluoroquinolone tolerance in Pseudomonas aeruginosa},
  url          = {http://dx.doi.org/10.1111/2049-632X.12174},
  volume       = {71},
  year         = {2014},
}

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