Open AccessA putative de‐ N ‐acetylase of the PIG ‐L superfamily affects fluoroquinolone tolerance in P seudomonas aeruginosa
Author(s) -
Liebens Veerle,
Defraine Valerie,
Van der Leyden Annelies,
De Groote Valerie N.,
Fierro Carolina,
Beullens Serge,
Verstraeten Natalie,
Kint Cyrielle,
Jans Ann,
Frangipani Emanuela,
Visca Paolo,
Marchal Kathleen,
Versées Wim,
Fauvart Maarten,
Michiels Jan
Publication year - 2014
Publication title -
pathogens and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.983
H-Index - 105
ISSN - 2049-632X
DOI - 10.1111/2049-632x.12174
Subject(s) - pseudomonas aeruginosa , superfamily , microbiology and biotechnology , biology , chemistry , bacteria , genetics , biochemistry , gene
A major cause of treatment failure of infections caused by P seudomonas 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 PA 14_66140/ PA 5002) 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.