Regulatory Landscape of the Pseudomonas aeruginosa Phosphoethanolamine Transferase Gene eptA in the Context of Colistin Resistance.

Content Provider	Europe PMC
Author	Cervoni, Matteo Sposato, Davide Lo Sciuto, Alessandra Imperi, Francesco
Editor	Solymosi, Norbert
Copyright Year	2023
Abstract	Pseudomonas aeruginosa has the genetic potential to acquire colistin resistance through the modification of lipopolysaccharide by the addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) or phosphoethanolamine (PEtN), mediated by the arn operon or the eptA gene, respectively. However, in vitro evolution experiments and genetic analysis of clinical isolates indicate that lipopolysaccharide modification with L-Ara4N is invariably preferred over PEtN addition as the colistin resistance mechanism in this bacterium. Since little is known about eptA regulation in P. aeruginosa, we generated luminescent derivatives of the reference strain P. aeruginosa PAO1 to monitor arn and eptA promoter activity. We performed transposon mutagenesis assays to compare the likelihood of acquiring mutations leading to arn or eptA induction and to identify eptA regulators. The analysis revealed that eptA was slightly induced under certain stress conditions, such as arginine or biotin depletion and accumulation of the signal molecule diadenosine tetraphosphate, but the induction did not confer colistin resistance. Moreover, we demonstrated that spontaneous mutations leading to colistin resistance invariably triggered arn rather than eptA expression, and that eptA was not induced in resistant mutants upon colistin exposure. Overall, these results suggest that the contribution of eptA to colistin resistance in P. aeruginosa may be limited by regulatory restraints.
Journal	Antibiotics (Basel, Switzerland)
Volume Number	12
PubMed Central reference number	PMC9952513
Issue Number	2
PubMed reference number	36830112
e-ISSN	20796382
DOI	10.3390/antibiotics12020200
Language	English
Publisher	MDPI
Publisher Date	2023-01-18
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	arn genes EptA L-aminoarabinose lipid A phosphoethanolamine transferase polymyxin reporter strain resistance spontaneous mutations transposon mutagenesis
Content Type	Text
Resource Type	Article
Subject	Biochemistry Pharmacology, Toxicology and Pharmaceutics Microbiology Pharmacology (medical) Infectious Diseases Microbiology (medical)