A putative de‐N‐acetylase of the PIG‐L superfamily affects fluoroquinolone tolerance in Pseudomonas aeruginosa. Issue 1 (24th April 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Pathogens and disease. Volume 71:Issue 1(2014:Jun.)
• Page Start: 39
• Page End: 54
• Publication Date: 2014-04-24
• Subjects: Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1111/2049-632X.12174
• Languages: English
• ISSNs: 2049-632X

Abstract

<abstract abstract-type="main" id="fim12174-abs-0001"> <title>Abstract</title> <p>A major cause of treatment failure of infections caused by <italic>Pseudomonas aeruginosa</italic> is the presence of antibiotic‐insensitive persister cells. The mechanism of persister formation in <italic>P. aeruginosa</italic> is largely unknown, and so far, only few genetic determinants have been linked to <italic>P. aeruginosa</italic> persistence. Based on a previous high‐throughput screening, we here present <italic>dnpA</italic> (de‐<italic>N</italic>‐acetylase involved in persistence; gene locus PA14_66140/PA5002) as a new gene involved in noninherited fluoroquinolone tolerance in <italic>P. aeruginosa</italic>. Fluoroquinolone tolerance of a <italic>dnpA</italic> mutant is strongly reduced both in planktonic culture and in a biofilm model, whereas overexpression of <italic>dnpA</italic> in the wild‐type strain increases the persister fraction. In addition, the susceptibility of the <italic>dnpA</italic> mutant to different classes of antibiotics is not affected. <italic>dnpA</italic> is part of the conserved LPS core oligosaccharide biosynthesis gene cluster. Based on primary sequence analysis, we predict that DnpA is a de‐<italic>N</italic>‐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 <italic>P. aeruginosa</italic> infections.</p> </abstract>