Pseudomonas aeruginosa responds to altered membrane phospholipid composition by adjusting the production of two-component systems, proteases and iron uptake proteins

Caliskan, Muttalip; Poschmann, Gereon; Gudzuhn, Mirja; Waldera-Lupa, Daniel M.; Molitor, Rebecka; Strunk, Christoph Heinrich; Streit, Wolfgang R.; Jaeger, Karl‐Erich; Kovačić, Filip

doi:10.1016/j.bbalip.2023.159317

Cited by 6 publications

(4 citation statements)

References 147 publications

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“…Comparative GC-MS profiling of FFAs secreted by P. aeruginosa Δ plaF and the wild-type cells revealed that PlaF can release medium-chain FFAs, including C10 and C14, from GPLs as in vitro substrates. This result corroborates our suggestion that PlaF exerts multiple physiological functions 48 through GPL degradation. 6 We observed that the chain length of the FFAs has a minor impact on the tilting transition.…”

Section: Discussionsupporting

confidence: 92%

Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-Regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa

Gentile,

Modric,

Thiele

et al. 2024

JACS Au

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PlaF is a membrane-bound phospholipase A 1 from Pseudomonas aeruginosa that is involved in remodeling membrane glycerophospholipids (GPLs) and modulating virulence-associated signaling and metabolic pathways. Previously, we identified the role of medium-chain free fatty acids (FFAs) in inhibiting PlaF activity and promoting homodimerization, yet the underlying molecular mechanism remained elusive. Here, we used unbiased and biased molecular dynamics simulations and free energy computations to assess how PlaF interacts with FFAs localized in the water milieu surrounding the bilayer or within the bilayer and how these interactions regulate PlaF activity. Mediumchain FFAs localized in the upper bilayer leaflet can stabilize inactive dimeric PlaF, likely through interactions with charged surface residues, as has been experimentally validated. Potential of mean force (PMF) computations indicate that membrane-bound FFAs may facilitate the activation of monomeric PlaF by lowering the activation barrier for changing into a tilted, active configuration. We estimated that the coupled equilibria of PlaF monomerization-dimerization and tilting at the physiological concentration of PlaF lead to the majority of PlaF forming inactive dimers when in a cell membrane loaded with decanoic acid (C10). This is in agreement with a suggested in vivo product feedback loop and gas chromatography−mass spectrometry profiling results, indicating that PlaF catalyzes the release of C10 from P. aeruginosa membranes. Additionally, we found that C10 in the water milieu can access the catalytic site of active monomeric PlaF, contributing to the competitive component of C10-mediated PlaF inhibition. Our study provides mechanistic insights into how medium-chain FFAs may regulate the activity of PlaF, a potential bacterial drug target.

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Section: Discussionsupporting

confidence: 92%

Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-Regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa

Gentile,

Modric,

Thiele

et al. 2024

JACS Au

Self Cite

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“…Others suppress drug efflux 7 . To explore whether ligation is negatively coupled with transport ( Figures 5A-5F ), PA14 iron 54 and both spermidine and putrescine uptake assays were initiated. 2,2’-bipyridyl depletion of intracellular iron facilitated measurement of exogenous Fe 2+ uptake through the chelation-dependent colorimetric change in ferrozine 55 .…”

Section: Resultsmentioning

confidence: 99%

Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death

Sharifian Gh.,

Norouzi,

Sorci

et al. 2024

Preprint

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Discovering new bacterial signaling pathways offers unique antibiotic strategies. Here, through an unbiased resistance screen of 3,884 gene knockout strains, we uncovered a previously unknown non-lytic bactericidal mechanism that sequentially couples three transporters and downstream transcription to lethally suppress respiration of the highly virulent P. aeruginosa strain PA14 - one of three species on the WHO's 'Priority 1: Critical' list. By targeting outer membrane YaiW, cationic lacritin peptide 'N-104' translocates into the periplasm where it ligates outer loops 4 and 2 of the inner membrane transporters FeoB and PotH, respectively, to suppress both ferrous iron and polyamine uptake. This broadly shuts down transcription of many biofilm-associated genes, including ferrous iron-dependent TauD and ExbB1. The mechanism is innate to the surface of the eye and is enhanced by synergistic coupling with thrombin peptide GKY20. This is the first example of an inhibitor of multiple bacterial transporters.

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“…51 Pseudomonas aeruginosa is more susceptible to reactive oxygen species due to differences in its cell membrane composition and metabolic processes. 52,53 Insoo et al (2009) reported that ZnO was a superior antimicrobial for Pseudomonas aeruginosa when compared to E. coli . 54 The study also shows that Pseudomonas aeruginosa microbes used to degrade the polymer (HDPE) had higher absorbance and colony-forming units than E. coli bacteria in the pure form of HDPE, but in the composite form, ZnO in the presence of CB (carbon black) showed a greater effect on Pseudomonas aeruginosa compared to E. coli .…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial polymer composites with anti-biofouling features for floating solar power plant applications: Effect of zinc oxide nanoparticles

Sahai,

Khan,

Jadhav

et al. 2023

Polymers from Renewable Resources

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Antimicrobial hybrid polymer composites are developed for application in floating solar power plants. To avoid the degradation of the floater because of microbes living in the water as well as possible biofouling, zinc oxide (ZnO) is used as an antimicrobial agent, varying the weight percent (1, 2, and 3 wt%) within the high-density polyethylene (HDPE) matrix, along with carbon black (CB) as a reinforcing agent (1, 1.5, 2, and 2.5 wt%). Escherichia coli (facultative anaerobic) and Pseudomonas aeruginosa (aerobic-facultatively anaerobic) gram-negative bacteria formed a biofilm on HDPE in a 96-well plate for 5 days. In vitro, biofilm formation was determined by measuring absorbance (A420) in crystal violet dye, and the colony-forming unit (CFU) was determined by the spread plating technique. The biofilm formation and disruption are observed through a scanning electron microscope (SEM), where both the CFU and the SEM revealed uniform formation of biofilm onto neat HDPE. The best performance in terms of reduced biofilm formation and biofouling onto HDPE floaters was achieved for E. coli (ZnO: 2 wt% and CB: 2 wt%), whereas for Pseudomonas aeruginosa (ZnO: 3 wt% and CB: 2 wt%). Application of greener polymers and nanoparticles for future studies is highly recommended.

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Pseudomonas aeruginosa responds to altered membrane phospholipid composition by adjusting the production of two-component systems, proteases and iron uptake proteins

Cited by 6 publications

References 147 publications

Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-Regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa

Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-Regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa

Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death

Antimicrobial polymer composites with anti-biofouling features for floating solar power plant applications: Effect of zinc oxide nanoparticles

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