Next Article in Journal
Tuberculosis Epidemiology and Badger (Meles meles) Spatial Ecology in a Hot-Spot Area in Atlantic Spain
Previous Article in Journal
NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ
Open AccessArticle

Genetic Basis and Physiological Effects of Lipid A Hydroxylation in Pseudomonas aeruginosa PAO1

1
Department of Science, Roma Tre University, 00146 Roma, Italy
2
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia–Fondazione Cenci Bolognetti, 00185 Roma, Italy
3
Department of Molecular Medicine, Sapienza University of Rome, 00185 Roma, Italy
*
Author to whom correspondence should be addressed.
These authors equally contributed to the work.
Pathogens 2019, 8(4), 291; https://doi.org/10.3390/pathogens8040291
Received: 4 November 2019 / Revised: 3 December 2019 / Accepted: 8 December 2019 / Published: 10 December 2019
(This article belongs to the Section Human Pathogens)
Modifications of the lipid A moiety of lipopolysaccharide influence the physicochemical properties of the outer membrane of Gram-negative bacteria. Some bacteria produce lipid A with a single hydroxylated secondary acyl chain. This hydroxylation is catalyzed by the dioxygenase LpxO, and is important for resistance to cationic antimicrobial peptides (e.g., polymyxins), survival in human blood, and pathogenicity in animal models. The lipid A of the human pathogen Pseudomonas aeruginosa can be hydroxylated in both secondary acyl chains, but the genetic basis and physiological role of these hydroxylations are still unknown. Through the generation of single and double deletion mutants in the lpxO1 and lpxO2 homologs of P. aeruginosa PAO1 and lipid A analysis by mass spectrometry, we demonstrate that both LpxO1 and LpxO2 are responsible for lipid A hydroxylation, likely acting on different secondary acyl chains. Lipid A hydroxylation does not appear to affect in vitro growth, cell wall stability, and resistance to human blood or antibiotics in P. aeruginosa. In contrast, it is required for infectivity in the Galleria mellonella infection model, without relevantly affecting in vivo persistence. Overall, these findings suggest a role for lipid A hydroxylation in P. aeruginosa virulence that could not be directly related to outer membrane integrity. View Full-Text
Keywords: biofilm; Galleria mellonella; hydroxylation; infection; lipid A; LpxO1; LpxO2; resistance; virulence biofilm; Galleria mellonella; hydroxylation; infection; lipid A; LpxO1; LpxO2; resistance; virulence
Show Figures

Figure 1

MDPI and ACS Style

Lo Sciuto, A.; Cervoni, M.; Stefanelli, R.; Spinnato, M.C.; Di Giamberardino, A.; Mancone, C.; Imperi, F. Genetic Basis and Physiological Effects of Lipid A Hydroxylation in Pseudomonas aeruginosa PAO1. Pathogens 2019, 8, 291.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop