Tracing the path of Quorum sensing molecules in cystic fibrosis mucus in a biomimetic in vitro permeability platform.
Quorum Sensing
Cystic Fibrosis
/ microbiology
Mucus
/ metabolism
Pseudomonas aeruginosa
/ metabolism
Humans
Permeability
Biomimetics
/ methods
Pyocyanine
/ metabolism
Pseudomonas Infections
/ metabolism
Lactones
/ metabolism
Quinolones
/ metabolism
Cell Membrane Permeability
Receptors, Aryl Hydrocarbon
/ metabolism
Biofilms
/ growth & development
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 10 2024
29 10 2024
Historique:
received:
09
07
2024
accepted:
22
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
P. aeruginosa employs specific quorum sensing (QS) mechanisms to orchestrate biofilm formation, enhancing resistance to host defences. In physiological conditions, QS molecules permeate the lung environment and cellular membrane to reach the cytoplasmic Aryl Hydrocarbon Receptor (AhR) that is pivotal for activating the immune response against infection. In pathological conditions like cystic fibrosis (CF) this interkingdom communication is altered, favouring P. aeruginosa persistence and chronic infection. Here, we aim to investigate the molecular journey of QS molecules from CF-like environments to the cytoplasm by quantifying via HPLC-MS the permeability of selected QS molecules (quinolones, lactones, and phenazines) through in vitro models of the two main biological lung barriers: CF-mucus and cellular membrane. While QS molecules not activating AhR exhibit intermediate permeability through the cellular membrane model (PAMPA) (1.0-4.0 × 10
Identifiants
pubmed: 39472521
doi: 10.1038/s41598-024-77375-w
pii: 10.1038/s41598-024-77375-w
doi:
Substances chimiques
Pyocyanine
9OQM399341
Lactones
0
Quinolones
0
Receptors, Aryl Hydrocarbon
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25907Informations de copyright
© 2024. The Author(s).
Références
Li, Z. et al. Infection and lung disease progression in children with cystic fibrosis. 293, 581–588 (2017).
Murray, M. P., Pentland, J. L., Turnbull, K., MacQuarrie, S. & Hill, A. T. Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis. Eur. Respir. J. 34, 361–364 (2008).
doi: 10.1183/09031936.00163208
Burns, J. L. et al. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J. Infect. Dis. 183, 444–452 (2001).
pubmed: 11133376
doi: 10.1086/318075
Murray, T. S., Egan, M. & Kazmierczak, B. I. Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients. Curr. Opin. Pediatr. 19, 83–88 (2007).
pubmed: 17224667
doi: 10.1097/MOP.0b013e3280123a5d
Ramsey, A. K. A. et al. Page 1 of 38 1–38 (2014).
Nadal Jimenez, P. et al. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol. Mol. Biol. Rev. 76, 46–65 (2012).
pmcid: 3294424
doi: 10.1128/MMBR.05007-11
Dietrich, L. E. P., Price-Whelan, A., Petersen, A., Whiteley, M. & Newman, D. K. The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol. Microbiol. 61, 1308–1321 (2006).
pubmed: 16879411
doi: 10.1111/j.1365-2958.2006.05306.x
Kendall, M. M. & Sperandio, V. What a dinner party! Mechanisms and functions of interkingdom signaling in host-pathogen associations. MBio 7, 1–14 (2016).
doi: 10.1128/mBio.01748-15
Fuqua, W. C., Winans, S. C. & Greenberg, E. P. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J. Bacteriol. 176, 269–275 (1994).
pubmed: 8288518
pmcid: 205046
doi: 10.1128/jb.176.2.269-275.1994
Lee, J. & Zhang, L. The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell 6, 26–41 (2015).
pubmed: 25249263
doi: 10.1007/s13238-014-0100-x
Hasseb, D. J. et al. Pseudomonas aeruginosa hypoxic or anaerobic biofilm infections within cystic fibrosis airways. Trends Microbiol. 17, 130–138 (2009).
doi: 10.1016/j.tim.2008.12.003
Ryan, H. et al. A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis. BMC Pulm. Med. 23, 1–10 (2023).
doi: 10.1186/s12890-023-02611-4
Hoboth, C. et al. Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis. J. Infect. Dis. 200, 118–130 (2009).
pubmed: 19459782
doi: 10.1086/599360
Rossi, E. et al. Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis. Nat. Rev. Microbiol. 19, 331–342 (2021).
pubmed: 33214718
doi: 10.1038/s41579-020-00477-5
Limoli, D. H., Jones, C. J. & Wozniak, D. J. Bacterial extracellular polysaccharides in biofilm formation and function. Microb. Biofilms 223–247. https://doi.org/10.1128/9781555817466.ch11 (2015).
Jacobs, H. M. et al. Mucoid Pseudomonas aeruginosa can produce calcium-gelled biofilms independent of the matrix components Psl and CdrA. J. Bacteriol. 204, 1–15 (2022).
doi: 10.1128/jb.00568-21
Malhotra, S. et al. Cystic fibrosis and Pseudomonas aeruginosa: the host–microbe interface sankalp. Br. Med. J. 3, 594 (2019).
Moradali, M. F., Ghods, S. & Rehm, B. H. A. Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Front. Cell. Infect. Microbiol. 7, 1–29 (2017).
doi: 10.3389/fcimb.2017.00039
Parad, R. B., Gerard, C. J., Zurakowski, D., Nichols, D. P. & Pier, G. B. Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype. Infect. Immun. 67, 4744–4750 (1999).
pubmed: 10456926
pmcid: 96804
doi: 10.1128/IAI.67.9.4744-4750.1999
Schuster, M. et al. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu. Rev. Microbiol. 67, 43–63 (2013).
pubmed: 23682605
doi: 10.1146/annurev-micro-092412-155635
Bernabè, G. et al. A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa. Front. Pharmacol. 13, 1–20 (2022).
doi: 10.3389/fphar.2022.996871
Ding, F. et al. The Pseudomonas aeruginosa orphan quorum sensing signal receptor QscR regulates global quorum sensing gene expression by activating a single linked operon. MBio 9, e01274–e01218 (2018).
pubmed: 30154259
pmcid: 6113619
doi: 10.1128/mBio.01274-18
Sperandio, V., Torres, A. G., Jarvis, B., Nataro, J. P. & Kaper, J. B. Bacteria-host communication: The language of hormones. Proc. Natl. Acad. Sci. U.S.A. 100, 8951–8956 (2003).
Major, J. et al. Endothelial AHR activity prevents lung barrier disruption in viral infection. Nature 621, 813–820 (2023).
pubmed: 37587341
pmcid: 7615136
doi: 10.1038/s41586-023-06287-y
Puccetti, M. et al. Towards targeting the aryl hydrocarbon receptor in cystic fibrosis. Mediat. Inflamm. 1–7 (2018).
Puccetti, M. et al. Targeted drug delivery technologies potentiate the overall therapeutic efficacy of an indole derivative in a mouse cystic fibrosis setting. Cells 10, 1622 (2021).
pubmed: 34209524
pmcid: 8305598
doi: 10.3390/cells10071601
Pariano, M. et al. Aryl hydrocarbon receptor agonism antagonizes the hypoxia-driven inflammation in cystic fibrosis. Am. J. Respir. Cell. Mol. Biol. 68, 288–301 (2023).
pubmed: 36252182
doi: 10.1165/rcmb.2022-0196OC
Moura-Alves, P. et al. Host monitoring of quorum sensing during Pseudomonas aeruginosa infection. Science 366 (2019).
Jahoor, A. et al. Peroxisome proliferator-activated receptors mediate host cell proinflammatory responses to Pseudomonas aeruginosa autoinducer. J. Bacteriol. 190, 4408–4415 (2008).
pubmed: 18178738
pmcid: 2446782
doi: 10.1128/JB.01444-07
Liu, Y. C., Chan, K. G. & Chang, C. Y. Modulation of host biology by Pseudomonas aeruginosa quorum sensing signal molecules: messengers or traitors. Front. Microbiol. 6, 1226 (2015).
pubmed: 26617576
pmcid: 4637427
doi: 10.3389/fmicb.2015.01226
Karlsson, T., Turkina, M. V., Yakymenko, O., Magnusson, K. E. & Vikström, E. The Pseudomonas aeruginosa N-acylhomoserine lactone quorum sensing molecules target IQGAP1 and modulate epithelial cell migration. PLoS Pathog. 8, e1002953 (2012).
pubmed: 23071436
pmcid: 3469656
doi: 10.1371/journal.ppat.1002953
Kansy, M., Senner, F. & Gubernator, K. Screening: parallel artificial membrane permeation assay in the description of. J. Med. Chem. 41, 1007–1010 (1998).
pubmed: 9544199
doi: 10.1021/jm970530e
Pacheco, D. P. et al. Disassembling the complexity of mucus barriers to develop a fast screening tool for early drug discovery. J. Mater. Chem. B 7, 4940–4952 (2019).
pubmed: 31411620
doi: 10.1039/C9TB00957D
Butnarasu, C., Caron, G., Pacheco, D. P., Petrini, P. & Visentin, S. Cystic fibrosis mucus model to design more efficient drug therapies. Mol. Pharm. 19, 520–531 (2022).
pubmed: 34936359
doi: 10.1021/acs.molpharmaceut.1c00644
Price-Whelan, A., Dietrich, L. E. P. & Newman, D. K. Rethinking ‘secondary’ metabolism: physiological roles for phenazine antibiotics. Nat. Chem. Biol. 2, 71–78 (2006).
pubmed: 16421586
doi: 10.1038/nchembio764
Butnarasu, C., Garbero, O. V., Petrini, P., Visai, L. & Visentin, S. Permeability assessment of a high-throughput mucosal platform. Pharmaceutics 15, 380 (2023).
pubmed: 36839702
pmcid: 9966667
doi: 10.3390/pharmaceutics15020380
Li, X., Mu, P., Wen, J. & Deng, Y. Carrier-mediated and energy-dependent uptake and efflux of deoxynivalenol in mammalian cells. Sci. Rep. 7, 1–10 (2017).
Ates, M., Kaynak, M. S. & Sahin, S. Effect of permeability enhancers on paracellular permeability of acyclovir. J. Pharm. Pharmacol. 68, 781–790 (2016).
doi: 10.1111/jphp.12551
Garti, N. Delivery and Controlled Release of Bioactives in Foods and Nutraceuticals (Woodhead Printing, 2008).
Davis, R. M., Muller, R. Y. & Haynes, K. A. Can the natural diversity of quorum-sensing advance synthetic biology? Front. Bioeng. Biotechnol. 3, 1–10 (2015).
Pearson, J. P., Van Delden, C. & Iglewski, B. H. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals. J. Bacteriol. 181, 1203–1210 (1999).
pubmed: 9973347
pmcid: 93498
doi: 10.1128/JB.181.4.1203-1210.1999
Mashburn, L. M. & Whiteley, M. Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature 437, 422–425 (2005).
pubmed: 16163359
doi: 10.1038/nature03925
Florez, C., Raab, J. E., Cooke, A. C. & Schertzer, J. W. Membrane distribution of the pseudomonas quinolone signal modulates outer membrane vesicle production in Pseudomonas aeruginosa. MBio 1–13 (2017).
Moura-Alves, P. et al. AhR sensing of bacterial pigments regulates antibacterial defence. Nature 512, 387–392 (2014).
pubmed: 25119038
doi: 10.1038/nature13684
Gloag, E. S., German, G. K., Stoodley, P. & Wozniak, D. J. Viscoelastic properties of Pseudomonas aeruginosa variant biofilms. Sci. Rep. 8, 1–11 (2018).
doi: 10.1038/s41598-018-28009-5
Chew, S. C. et al. Dynamic remodeling of microbial biofilms by functionally distinct exopolysaccharides. MBio 5, 1–11 (2014).
doi: 10.1128/mBio.01536-14
Sardelli, L. et al. Technological tools and strategies for culturing human gut microbiota in engineered in vitro models. Biotechnol. Bioeng. 118, 2886–2905 (2021).
pubmed: 33990954
pmcid: 8361989
doi: 10.1002/bit.27816
Sardelli, L. et al. Towards bioinspired: in vitro models of intestinal mucus. RSC Adv. 9, 15887–15899 (2019).
pubmed: 35521409
pmcid: 9064393
doi: 10.1039/C9RA02368B
Witten, J., Samad, T. & Ribbeck, K. Molecular characterization of mucus binding. Biomacromolecules 20, 1505–1513 (2019).
pubmed: 30779551
pmcid: 6581564
doi: 10.1021/acs.biomac.8b01467
Sigurdsson, H. H., Kirch, J. & Lehr, C. M. Mucus as a barrier to lipophilic drugs. Int. J. Pharm. 453, 56–64 (2013).
pubmed: 23727593
doi: 10.1016/j.ijpharm.2013.05.040
Ryall, B. et al. The mucoid switch in Pseudomonas aeruginosa represses quorum sensing systems and leads to complex changes to stationary phase virulence factor regulation. PLoS ONE 9, e96166 (2014).
pubmed: 24852379
pmcid: 4031085
doi: 10.1371/journal.pone.0096166
Hill, D. B. et al. Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH. Eur. Respir. J. 52, 1–18 (2018).
doi: 10.1183/13993003.01297-2018
Massip-Copiz, M. M. & Santa-Coloma, T. A. Extracellular pH and lung infections in cystic fibrosis. Eur. J. Cell. Biol. 97, 402–410 (2018).
pubmed: 29933921
doi: 10.1016/j.ejcb.2018.06.001
Tate, S., MacGregor, G., Davis, M., Innes, J. A. & Greening, A. P. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax 57, 926–929 (2002).
pubmed: 12403872
pmcid: 1746233
doi: 10.1136/thorax.57.11.926
Morales, L. D., Av-Gay, Y. & Murphy, M. E. P. Acidic pH modulates Burkholderia cenocepacia antimicrobial susceptibility in the cystic fibrosis nutritional environment. Microbiol. Spectr. 11, 1–13 (2023).
doi: 10.1128/spectrum.02731-23
Mao, M. et al. Study on the interactions between oral mucin and cyanidin 3-O-glucoside: the effect of oxidized quinone. Food Bioprocess. Technol. 17, 1335–1345 (2024).
doi: 10.1007/s11947-023-03207-w