Pseudomonas aeruginosa Virulence Factors: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Yvaine Wei and Version 1 by Pulin Che.

Pseudomonas (P.) aeruginosa is an opportunistic pathogen that causes serious infections and hospital-acquired pneumonia in immunocompromised patients. The poor clinical outcome of P. aeruginosa-induced pneumonia is ascribed to its ability to disrupt lung barrier integrity, leading to the development of lung edema and bacteremia. Airway epithelial and endothelial cells are important architecture blocks that protect the lung from invading pathogens. P. aeruginosa produces a number of virulence factors that can modulate barrier function, directly or indirectly, through exploiting cytoskeleton networks and intercellular junctional complexes in eukaryotic cells.

  • Pseudomonas aeruginosa
  • virulence factors
  • actin cytoskeleton

1. P. aeruginosa Targets Cytoskeletal Network in Lung Endothelial Cells

Endothelial cells are specialized cells that line the internal surface of blood vessels and are responsible for the maintenance of vascular permeability. Although serving as a barrier between blood and interstitial fluid, the lung endothelium is composed of a single layer of endothelial cells, making it vulnerable to attack by P. aeruginosa virulence factors. Following disruption of the epithelial barrier, P. aeruginosa virulence factors have access to the endothelium, where proteases and toxins released from P. aeruginosa further disrupt endothelial tight junctions [62][1]. As a consequence of dysregulated endothelial cell barriers, P. aeruginosa can migrate into the bloodstream and lead to bacteremia and cause a fatal outcomes [63][2]. However, compared to airway epithelium, a small number of studies have investigated the destructive effects of P. aeruginosa virulence factors on lung endothelium [28,50,62,64,65][3][4][1][5][6]. Endothelium presents similar yet distinct intercellular junctional components when compared to those of the epithelium. For example, instead of E-cadherin expressed by epithelial AJs, endothelial AJs present VE-cadherin, an endothelial-specific cadherin [66,67][7][8]. P. aeruginosa elastase cleaves VE-cadherin [21,62][9][1]. Moreover, ExoS and ExoT increase paracellular permeability across endothelial cell monolayers through integrin αvβ5 with activation of RhoA signaling [28,68,69][3][10][11]. In addition, compared to the junctional complex in epithelium, the endothelium presents intermingled TJs and AJs [70][12]. Interestingly, recent evidence suggests that actin assembly at TJs and AJs are regulated through distinctive mechanisms [71,72][13][14]. Lung endothelium and epithelium also share some similar mechanisms in the role of cytoskeleton dynamics in barrier function in response to P. aeruginosa infection. Neural Wiskott–Aldrich syndrome protein (NWASP) plays a critical role in cytoskeleton dynamics and regulates barrier integrity through Rho GTPase signaling and cytoskeletal reorganization in lung endothelial and epithelial cells in response to P. aeruginosa and transforming growth factor beta-1 [64,73][5][15]. It has recently been noted that barrier function is more strictly controlled with 10 times higher transendothelial electrical resistance and more developed intercellular junctions in lung microvascular endothelium in comparison to lung macrovascular endothelium [74,75,76,77][16][17][18][19]. Additional studies are needed to understand the molecular mechanisms by which P. aeruginosa virulence factors breach the lung microvascular endothelium by modulation of cytoskeletal structures and cytoskeletal regulatory proteins.

2. Cytoskeletal Regulation by P. aeruginosa Virulence Factors

Regulation of Lung Permeability by Virulence Factors Belonging to

2.1. Regulation of Lung Permeability by Virulence Factors Belonging to

P. aeruginosa

Type III Secretion System

Type III secretion system (T3SS) is the major contributor to P. aeruginosa-induced virulence [78,79,80,81][20][21][22][23]. Epithelial cells are especially sensitive to the effects of T3SS toxins [25,80,81,82,83][24][22][23][25][26]. P. aeruginosa T3SS translocates four exoenzymes (ExoS, ExoT, ExoY, and ExoU) into host cells (Figure 21). These exoenzymes have overlapping, yet distinct pathways to target cytoskeleton components and associated junctional complex, causing cell morphological changes and intercellular junction disruption, leading to a loss of barrier integrity. The interactions of these type III exoenzymes with cytoskeleton components are important in the pathogenesis of P. aeruginosa infection.
Toxins 13 00776 g002 550
Figure 21. Schematic depicting T3SS exoenzymes and their interaction with host intracellular pathways contributing to barrier disruption. These events result in actin stress fiber formation, cytoskeleton rearrangement, and disruption of intercellular junctions, following with increased permeability.

3. Regulation of Lung Permeability by

2.2. Regulation of Lung Permeability by

P. aeruginosa

Secreted Virulence Factors

3.1. Elastase

2.2.1. Elastase

P. aeruginosa elastase (PE) is a secreted metalloproteinase with highly efficient proteolytic activity on a number of host structural proteins in airway epithelium [120,121,122,123,124,125][27][28][29][30][31][32]. It has been reported that PE can transiently disintegrate and redistribute tight junction proteins OCLN and ZO-1, induce cleavage of VE-cadherin, and cause actin cytoskeleton reorganization [22,23,62,126,127,128][33][34][1][35][36][37]. By using the B.V strain that is known for its high elastase activity, it has been shown that PE is capable of completely degrading ZO-1 and significantly degrading OCLN [127][36]. Besides targeting on tight junction proteins, PE has tissue-damaging activities. In addition, PE can degrade lung elastin, an important structural protein for maintaining blood vessel integrity [123[30][38],129], as well as matrix proteins including laminin and collagen (type III and type IV), leading to basement membrane impairment [130,131,132][39][40][41].

3.2. Exotoxin A

2.2.2. Exotoxin A

P. aeruginosa produces a highly toxic virulence factor exotoxin A (ExoA) which is released into extracellular medium by type 2 secretion system (T2SS) [133,134][42][43]. It has ADP-ribosylation activity and affects the protein synthesis processes in host cells. ExoA has been shown to delay wound repair in the animal cutaneious injury model through its effects on cytoskeleton remodeling [135][44]. Treatment with ExoA reduces TJs proteins ZO-1 and ZO-2 and increases paracellular permeability in type II pneumocyte cultures [23][34]. However, the exact mechanism undergoing ExoA-mediated epithelial barrier damage still need further studies.

32.3. Regulation of Lung Permeability by P. aeruginosa Surface-Bound Virulence Factors

32.3.1. Pilus and Flagellum

Type IV pilus and flagellum are important surface structural components for P. aeruginosa attachment to cell surface and are critical in preparation for T3SS toxin injection [136,137][45][46]. Due to the nature as P. aeruginosa surface structure, pilus and flagellum are likely to have roles beyond mediating an initial attachment to the host surface. Evidence show that pilus and flagellum are required for transmigration across epithelial cell junctions [136,137][45][46]. Recently, pilus has been shown to preferentially interact with the cell basolateral domain and T3SS effectors are only injected into host cells through their basolateral membrane domain [136,137,138][45][46][47]. Internalization of P. aeruginosa in the epithelial basolateral surface requires flagellum binding to heparan sulfate, with subsequent signaling activation of epidermal growth factor receptor (EGFR), phosphoinositide 3-kinases (PI3K), and protein kinase B (AKT) [138][47]. These findings suggest these surface-bound virulence factors may play an important role in mediating P. aeruginosa transmigration through paracellular route.

32.3.2. Lipopolysccharide

Lipopolysccharide (LPS) is a major structure component which is integrated in the P. aeruginosa cell wall and plays an important role in bacterium–host interactions [139][48]. LPS is a pro-inflammatory mediator which can increase airway epithelial permeability [140][49]. LPS-induced F-actin rearrangement and actin assembly are important for LPS signaling [59][50]. However, molecular mechanisms for LPS-induced endothelial cell permeability are still not well understood.

32.4. Regulation of Lung Permeability by Quorum Sensing and Other P. aeruginosa Virulence Factors

Quorum sensing (QS) is a specialized cell density-dependent regulation system in bacteria [141,142,143][51][52][53]. These bacterial signals also modulate mammalian airway epithelial cell responses to the pathogen in a process called interkingdom signaling. N-(3-Oxododecanoyl)-L-homoserine lactone (C12) is a small molecule quorum-sensing signal produced by a P. aeruginosa lasR-lasI QS system [144,145][54][55]. In addition to the regulation of P. aeruginosa population behavior, C12 also regulates a range of complex biological processes in host cells. In human epithelial Caco-2 cells, C12 induces a decrease in transepithelial electrical resistance (TER), an increase in paracellular flux, a reduction in the expression and distribution of ZO-1 and OCLN, and reorganization of F-actin through activation of p38 and p42/44 pathways [146][56]. In intestinal epithelial cells, C12 alters the phosphorylation status of cell junctional components, including E-cadherin, beta-catenin, OCLN, ZO-1, and ZO-3, and JAM-A. In addition, the changes in phosphorylation status of regulatory proteins disrupt the association between junctional components and result in a loss of epithelial barrier and increased paracellular permeability [24,147][57][58]. C12 also induces degradation and de-location of TJs proteins (OCLN and tricellulin) in intestinal epithelial Caco-2 cells [148][59]. These findings collectively indicate that C12 induces epithelial paracellular permeability possibly through a mechanism that mediates the disassembly of intercellular links. C12 induces myofibroblast differentiation in vitro and in vivo for accelerated wound healing [149][60]. In cultured nonpolarized airway epithelial cells, C12 induces massive morphological changes of cell structure with perturbed gap junction shortly after application [150][61]. C12 may also facilitate dissemination of virus into bloodstream [151][62].

Rhamnolipids

P. aeruginosa produces biosurfactants called rhamnolipids [152,153][63][64]. Rhamnolipids act as a potent detergent and have been reported to disrupt intercellular junctions in sheep tracheal epithelium at high concentrations [154][65]. Rhamnolipids induce ciliostasis of airway epithelial cells and may disrupt their barrier function, allowing invasion of pseudomonas [12][66]. Alzheimer’s disease (AD) has been attributed to chronic bacterial infections, and the levels of rhamnolipids in sera and cerebrospinal fluid of AD patients are significantly increased when compared to controls [155][67]. However, the meaning of the increased rhamnolipids levels in AD patients and AD pathogenesis is unclear so far.

References

  1. Golovkine, G.; Faudry, E.; Bouillot, S.; Voulhoux, R.; Attree, I.; Huber, P. VE-cadherin cleavage by LasB protease from Pseudomonas aeruginosa facilitates type III secretion system toxicity in endothelial cells. PLoS Pathog. 2014, 10, e1003939.
  2. Sadikot, R.T.; Blackwell, T.S.; Christman, J.W.; Prince, A.S. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am. J. Respir. Crit. Care Med. 2005, 171, 1209–1223.
  3. Ganter, M.T.; Roux, J.; Su, G.; Lynch, S.V.; Deutschman, C.S.; Weiss, Y.G.; Christiaans, S.C.; Myazawa, B.; Kipnis, E.; Wiener-Kronish, J.P.; et al. Role of small GTPases and alphavbeta5 integrin in Pseudomonas aeruginosa-induced increase in lung endothelial permeability. Am. J. Respir. Cell Mol. Biol. 2009, 40, 108–118.
  4. Huber, P.; Bouillot, S.; Elsen, S.; Attree, I. Sequential inactivation of Rho GTPases and Lim kinase by Pseudomonas aeruginosa toxins ExoS and ExoT leads to endothelial monolayer breakdown. Cell. Mol. Life Sci. 2014, 71, 1927–1941.
  5. Che, P.; Wagener, B.M.; Zhao, X.; Brandon, A.P.; Evans, C.A.; Cai, G.Q.; Zhao, R.; Xu, Z.X.; Han, X.; Pittet, J.F.; et al. Neuronal Wiskott-Aldrich syndrome protein regulates Pseudomonas aeruginosa-induced lung vascular permeability through the modulation of actin cytoskeletal dynamics. FASEB J. 2020, 34, 3305–3317.
  6. Elsen, S.; Huber, P.; Bouillot, S.; Coute, Y.; Fournier, P.; Dubois, Y.; Timsit, J.F.; Maurin, M.; Attree, I. A type III secretion negative clinical strain of Pseudomonas aeruginosa employs a two-partner secreted exolysin to induce hemorrhagic pneumonia. Cell Host. Microbe 2014, 15, 164–176.
  7. Lampugnani, M.G.; Resnati, M.; Raiteri, M.; Pigott, R.; Pisacane, A.; Houen, G.; Ruco, L.P.; Dejana, E. A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J. Cell Biol. 1992, 118, 1511–1522.
  8. Breier, G.; Breviario, F.; Caveda, L.; Berthier, R.; Schnurch, H.; Gotsch, U.; Vestweber, D.; Risau, W.; Dejana, E. Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Blood 1996, 87, 630–641.
  9. Beaufort, N.; Corvazier, E.; Mlanaoindrou, S.; de Bentzmann, S.; Pidard, D. Disruption of the endothelial barrier by proteases from the bacterial pathogen Pseudomonas aeruginosa: Implication of matrilysis and receptor cleavage. PLoS ONE 2013, 8, e75708.
  10. Ganter, M.T.; Roux, J.; Miyazawa, B.; Howard, M.; Frank, J.A.; Su, G.; Sheppard, D.; Violette, S.M.; Weinreb, P.H.; Horan, G.S.; et al. Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circ. Res. 2008, 102, 804–812.
  11. Su, G.; Hodnett, M.; Wu, N.; Atakilit, A.; Kosinski, C.; Godzich, M.; Huang, X.Z.; Kim, J.K.; Frank, J.A.; Matthay, M.A.; et al. Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function. Am. J. Respir. Cell Mol. Biol. 2007, 36, 377–386.
  12. Wallez, Y.; Huber, P. Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis. Biochim. Biophys. Acta 2008, 1778, 794–809.
  13. Belardi, B.; Hamkins-Indik, T.; Harris, A.R.; Kim, J.; Xu, K.; Fletcher, D.A. A Weak Link with Actin Organizes Tight Junctions to Control Epithelial Permeability. Dev. Cell 2020, 54, 792–804.e7.
  14. Hansen, S.D.; Kwiatkowski, A.V.; Ouyang, C.Y.; Liu, H.; Pokutta, S.; Watkins, S.C.; Volkmann, N.; Hanein, D.; Weis, W.I.; Mullins, R.D.; et al. alphaE-catenin actin-binding domain alters actin filament conformation and regulates binding of nucleation and disassembly factors. Mol. Biol. Cell 2013, 24, 3710–3720.
  15. Wagener, B.M.; Hu, M.; Zheng, A.; Zhao, X.; Che, P.; Brandon, A.; Anjum, N.; Snapper, S.; Creighton, J.; Guan, J.L.; et al. Neuronal Wiskott-Aldrich syndrome protein regulates TGF-beta1-mediated lung vascular permeability. FASEB J. 2016, 30, 2557–2569.
  16. Blum, M.S.; Toninelli, E.; Anderson, J.M.; Balda, M.S.; Zhou, J.; O’Donnell, L.; Pardi, R.; Bender, J.R. Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines. Am. J. Physiol. 1997, 273, H286–H294.
  17. Schnitzer, J.E.; Siflinger-Birnboim, A.; Del Vecchio, P.J.; Malik, A.B. Segmental differentiation of permeability, protein glycosylation, and morphology of cultured bovine lung vascular endothelium. Biochem. Biophys. Res. Commun. 1994, 199, 11–19.
  18. Saguil, A.; Fargo, M. Acute respiratory distress syndrome: Diagnosis and management. Am. Fam Physician 2012, 85, 352–358.
  19. Stevens, T. Functional and molecular heterogeneity of pulmonary endothelial cells. Proc. Am. Thorac. Soc. 2011, 8, 453–457.
  20. Horna, G.; Ruiz, J. Type 3 secretion system of Pseudomonas aeruginosa. Microbiol. Res. 2021, 246, 126719.
  21. Deng, W.; Marshall, N.C.; Rowland, J.L.; McCoy, J.M.; Worrall, L.J.; Santos, A.S.; Strynadka, N.C.J.; Finlay, B.B. Assembly, structure, function and regulation of type III secretion systems. Nat. Rev. Microbiol. 2017, 15, 323–337.
  22. Williams McMackin, E.A.; Djapgne, L.; Corley, J.M.; Yahr, T.L. Fitting Pieces into the Puzzle of Pseudomonas aeruginosa Type III Secretion System Gene Expression. J. Bacteriol. 2019, 201.
  23. Bohn, E.; Sonnabend, M.; Klein, K.; Autenrieth, I.B. Bacterial adhesion and host cell factors leading to effector protein injection by type III secretion system. Int. J. Med. Microbiol. 2019, 309, 344–350.
  24. Soong, G.; Parker, D.; Magargee, M.; Prince, A.S. The type III toxins of Pseudomonas aeruginosa disrupt epithelial barrier function. J. Bacteriol. 2008, 190, 2814–2821.
  25. Rucks, E.A.; Fraylick, J.E.; Brandt, L.M.; Vincent, T.S.; Olson, J.C. Cell line differences in bacterially translocated ExoS ADP-ribosyltransferase substrate specificity. Microbiology (Reading) 2003, 149, 319–331.
  26. Kurahashi, K.; Kajikawa, O.; Sawa, T.; Ohara, M.; Gropper, M.A.; Frank, D.W.; Martin, T.R.; Wiener-Kronish, J.P. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J. Clin. Investig. 1999, 104, 743–750.
  27. Janda, J.M.; Bottone, E.J. Pseudomonas aeruginosa enzyme profiling: Predictor of potential invasiveness and use as an epidemiological tool. J. Clin. Microbiol. 1981, 14, 55–60.
  28. Bleves, S.; Viarre, V.; Salacha, R.; Michel, G.P.; Filloux, A.; Voulhoux, R. Protein secretion systems in Pseudomonas aeruginosa: A wealth of pathogenic weapons. Int. J. Med. Microbiol. 2010, 300, 534–543.
  29. Woods, D.E.; Cryz, S.J.; Friedman, R.L.; Iglewski, B.H. Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats. Infect. Immun. 1982, 36, 1223–1228.
  30. Azghani, A.O.; Connelly, J.C.; Peterson, B.T.; Gray, L.D.; Collins, M.L.; Johnson, A.R. Effects of Pseudomonas aeruginosa elastase on alveolar epithelial permeability in guinea pigs. Infect. Immun. 1990, 58, 433–438.
  31. Peters, J.E.; Galloway, D.R. Purification and characterization of an active fragment of the LasA protein from Pseudomonas aeruginosa: Enhancement of elastase activity. J. Bacteriol. 1990, 172, 2236–2240.
  32. Everett, M.J.; Davies, D.T. Pseudomonas aeruginosa elastase (LasB) as a therapeutic target. Drug Discov. Today 2021, 26, 2108–2123.
  33. Nomura, K.; Obata, K.; Keira, T.; Miyata, R.; Hirakawa, S.; Takano, K.; Kohno, T.; Sawada, N.; Himi, T.; Kojima, T. Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells. Respir. Res. 2014, 15, 21.
  34. Azghani, A.O. Pseudomonas aeruginosa and epithelial permeability: Role of virulence factors elastase and exotoxin A. Am. J. Respir. Cell Mol. Biol. 1996, 15, 132–140.
  35. Azghani, A.O.; Miller, E.J.; Peterson, B.T. Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability. Lung 2000, 178, 261–269.
  36. Li, J.; Ramezanpour, M.; Fong, S.A.; Cooksley, C.; Murphy, J.; Suzuki, M.; Psaltis, A.J.; Wormald, P.J.; Vreugde, S. Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity. Front. Cell Infect. Microbiol. 2019, 9, 38.
  37. Clark, C.A.; Thomas, L.K.; Azghani, A.O. Inhibition of protein kinase C attenuates Pseudomonas aeruginosa elastase-induced epithelial barrier disruption. Am. J. Respir. Cell Mol. Biol. 2011, 45, 1263–1271.
  38. Saulnier, J.M.; Curtil, F.M.; Duclos, M.C.; Wallach, J.M. Elastolytic activity of Pseudomonas aeruginosa elastase. Biochim. Biophys. Acta 1989, 995, 285–290.
  39. Bejarano, P.A.; Langeveld, J.P.; Hudson, B.G.; Noelken, M.E. Degradation of basement membranes by Pseudomonas aeruginosa elastase. Infect. Immun. 1989, 57, 3783–3787.
  40. Heck, L.W.; Morihara, K.; Abrahamson, D.R. Degradation of soluble laminin and depletion of tissue-associated basement membrane laminin by Pseudomonas aeruginosa elastase and alkaline protease. Infect. Immun. 1986, 54, 149–153.
  41. Heck, L.W.; Morihara, K.; McRae, W.B.; Miller, E.J. Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase. Infect. Immun. 1986, 51, 115–118.
  42. Michalska, M.; Wolf, P. Pseudomonas Exotoxin A: Optimized by evolution for effective killing. Front. Microbiol. 2015, 6, 963.
  43. Mazor, R.; Pastan, I. Immunogenicity of Immunotoxins Containing Pseudomonas Exotoxin A: Causes, Consequences, and Mitigation. Front. Immunol. 2020, 11, 1261.
  44. Heggers, J.P.; Haydon, S.; Ko, F.; Hayward, P.G.; Carp, S.; Robson, M.C. Pseudomonas aeruginosa exotoxin A: Its role in retardation of wound healing: The 1992 Lindberg Award. J. Burn Care Rehabil. 1992, 13, 512–518.
  45. Heiniger, R.W.; Winther-Larsen, H.C.; Pickles, R.J.; Koomey, M.; Wolfgang, M.C. Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesin. Cell Microbiol. 2010, 12, 1158–1173.
  46. Hayashi, N.; Nishizawa, H.; Kitao, S.; Deguchi, S.; Nakamura, T.; Fujimoto, A.; Shikata, M.; Gotoh, N. Pseudomonas aeruginosa injects type III effector ExoS into epithelial cells through the function of type IV pili. FEBS Lett. 2015, 589, 890–896.
  47. Bucior, I.; Pielage, J.F.; Engel, J.N. Pseudomonas aeruginosa pili and flagella mediate distinct binding and signaling events at the apical and basolateral surface of airway epithelium. PLoS Pathog. 2012, 8, e1002616.
  48. Huszczynski, S.M.; Lam, J.S.; Khursigara, C.M. The Role of Pseudomonas aeruginosa Lipopolysaccharide in Bacterial Pathogenesis and Physiology. Pathogens 2019, 9, 6.
  49. Eutamene, H.; Theodorou, V.; Schmidlin, F.; Tondereau, V.; Garcia-Villar, R.; Salvador-Cartier, C.; Chovet, M.; Bertrand, C.; Bueno, L. LPS-induced lung inflammation is linked to increased epithelial permeability: Role of MLCK. Eur. Respir. J. 2005, 25, 789–796.
  50. Chakravortty, D.; Nanda Kumar, K.S. Bacterial lipopolysaccharide induces cytoskeletal rearrangement in small intestinal lamina propria fibroblasts: Actin assembly is essential for lipopolysaccharide signaling. Biochim. Biophys. Acta 2000, 1500, 125–136.
  51. Schuster, M.; Greenberg, E.P. A network of networks: Quorum-sensing gene regulation in Pseudomonas aeruginosa. Int. J. Med. Microbiol. 2006, 296, 73–81.
  52. Chadha, J.; Harjai, K.; Chhibber, S. Revisiting the virulence hallmarks of Pseudomonas aeruginosa: A chronicle through the perspective of quorum sensing. Environ. Microbiol. 2021.
  53. Kariminik, A.; Baseri-Salehi, M.; Kheirkhah, B. Pseudomonas aeruginosa quorum sensing modulates immune responses: An updated review article. Immunol. Lett. 2017, 190, 1–6.
  54. Pearson, J.P.; Gray, K.M.; Passador, L.; Tucker, K.D.; Eberhard, A.; Iglewski, B.H.; Greenberg, E.P. Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc. Natl. Acad. Sci. USA 1994, 91, 197–201.
  55. Guo, J.; Yoshida, K.; Ikegame, M.; Okamura, H. Quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone: An all-rounder in mammalian cell modification. J. Oral. Biosci. 2020, 62, 16–29.
  56. Vikstrom, E.; Tafazoli, F.; Magnusson, K.E. Pseudomonas aeruginosa quorum sensing molecule N-(3 oxododecanoyl)-l-homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells. FEBS Lett. 2006, 580, 6921–6928.
  57. Vikstrom, E.; Bui, L.; Konradsson, P.; Magnusson, K.E. The junctional integrity of epithelial cells is modulated by Pseudomonas aeruginosa quorum sensing molecule through phosphorylation-dependent mechanisms. Exp. Cell Res. 2009, 315, 313–326.
  58. Vikstrom, E.; Bui, L.; Konradsson, P.; Magnusson, K.E. Role of calcium signalling and phosphorylations in disruption of the epithelial junctions by Pseudomonas aeruginosa quorum sensing molecule. Eur. J. Cell Biol. 2010, 89, 584–597.
  59. Eum, S.Y.; Jaraki, D.; Bertrand, L.; Andras, I.E.; Toborek, M. Disruption of epithelial barrier by quorum-sensing N-3-(oxododecanoyl)-homoserine lactone is mediated by matrix metalloproteinases. Am. J. Physiol. Gastrointest Liver Physiol. 2014, 306, G992–G1001.
  60. Nakagami, G.; Minematsu, T.; Asada, M.; Nagase, T.; Akase, T.; Huang, L.; Morohoshi, T.; Ikeda, T.; Ohta, Y.; Sanada, H. The Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl) homoserine lactone can accelerate cutaneous wound healing through myofibroblast differentiation in rats. FEMS Immunol. Med. Microbiol. 2011, 62, 157–163.
  61. Losa, D.; Kohler, T.; Bacchetta, M.; Saab, J.B.; Frieden, M.; van Delden, C.; Chanson, M. Airway Epithelial Cell Integrity Protects from Cytotoxicity of Pseudomonas aeruginosa Quorum-Sensing Signals. Am. J. Respir. Cell Mol. Biol. 2015, 53, 265–275.
  62. Qiao, J.; Cao, Y.; Zabaleta, J.; Yang, L.; Dai, L.; Qin, Z. Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules. J. Virol. 2018, 92.
  63. Jensen, P.O.; Bjarnsholt, T.; Phipps, R.; Rasmussen, T.B.; Calum, H.; Christoffersen, L.; Moser, C.; Williams, P.; Pressler, T.; Givskov, M.; et al. Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology 2007, 153, 1329–1338.
  64. Soberon-Chavez, G.; Gonzalez-Valdez, A.; Soto-Aceves, M.P.; Cocotl-Yanez, M. Rhamnolipids produced by Pseudomonas: From molecular genetics to the market. Microb. Biotechnol. 2021, 14, 136–146.
  65. Graham, A.; Steel, D.M.; Wilson, R.; Cole, P.J.; Alton, E.W.; Geddes, D.M. Effects of purified Pseudomonas rhamnolipids on bioelectric properties of sheep tracheal epithelium. Exp. Lung Res. 1993, 19, 77–89.
  66. Zulianello, L.; Canard, C.; Kohler, T.; Caille, D.; Lacroix, J.S.; Meda, P. Rhamnolipids are virulence factors that promote early infiltration of primary human airway epithelia by Pseudomonas aeruginosa. Infect. Immun. 2006, 74, 3134–3147.
  67. Andreadou, E.; Pantazaki, A.A.; Daniilidou, M.; Tsolaki, M. Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease. J. Alzheimers Dis. 2017, 59, 209–222.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Video Production Service
Feedback