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Medical Microbiology and Immunology

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03.08.2019 | Original Investigation

Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-l-homoserine lactone triggers mitochondrial dysfunction and apoptosis in neutrophils through calcium signaling

verfasst von: Pradeep Kumar Singh, Vivek Kumar Yadav, Manmohit Kalia, Deepmala Sharma, Deepak Pandey, Vishnu Agarwal

Erschienen in: Medical Microbiology and Immunology | Ausgabe 6/2019

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Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that utilizes the quorum-sensing (QS) process to regulate the production of different virulence factors and biofilm. N-3-oxo-dodecanoyl-l-homoserine lactone (C12) is a key QS molecule of P. aeruginosa which interacts with the mammalian immune cells and modulates their function. Here, we investigated the molecular mechanism of C12-induced apoptosis in neutrophils. Our data show that C12 causes apoptosis in neutrophils through an elevation in cytosolic and mitochondrial Ca²⁺ levels. Besides, C12 induces phosphatidylserine (PS) exposure, mitochondrial membrane potential (MMP) depolarization, mitochondrial permeability transition pore (MPTP) formation and mitochondrial reactive oxygen species (mROS) generation. C12-induced rise in intracellular Ca²⁺ level is majorly contributed by endoplasmic reticulum store through the activation of inositol 1, 4, 5-triphosphate receptor. Intracellular calcium chelation inhibited C12-induced mitochondrial dysfunction and apoptosis. Further, inhibition of mitochondrial Ca²⁺ uniporter by ruthenium red or Ru360 abrogated C12-induced mitochondrial Ca²⁺ uptake, MMP loss, MPTP opening, mROS production, and PS exposure. These mechanistic insights are expected to provide a better understanding of the role of C12 in P. aeruginosa pathogenesis.

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Lyczak JB, Cannon CL, Pier GB (2000) Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2:1051–1060. https://doi.org/10.1016/S1286-4579(00)01259-4 CrossRefPubMed

Winstanley C, O’Brien S, Brockhurst MA (2016) Pseudomonas aeruginosa evolutionary adaptation and diversification in cystic fibrosis chronic lung infections. Trends Microbiol 24:327–337. https://doi.org/10.1016/j.tim.2016.01.008 CrossRefPubMedPubMedCentral

Hoiby N, Flensborg EW, Beck B et al (1977) Pseudomonas aeruginosa infection in cystic fibrosis. Diagnostic and prognostic significance of Pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis. Scand J Respir Dis 58:65–79PubMed

Richards MJ, Edwards JR, Culver DH, Gaynes RP (1999) Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 27:887–892CrossRef

Winstanley C, Fothergill JL (2009) The role of quorum sensing in chronic cystic fibrosis Pseudomonas aeruginosa infections. FEMS Microbiol Lett 290:1–9. https://doi.org/10.1111/j.1574-6968.2008.01394.x CrossRefPubMed

Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199. https://doi.org/10.1146/annurev.micro.55.1.165 CrossRefPubMed

Pesci EC, Pearson JP, Seed PC, Iglewski BH (1997) Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol 179:3127–3132. https://doi.org/10.1128/jb.179.10.3127-3132 CrossRefPubMedPubMedCentral

Lee J, Zhang L (2015) The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell 6:26–41. https://doi.org/10.1007/s13238-014-0100-x CrossRefPubMed

Williams SC, Patterson EK, Carty NL et al (2004) Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells. J Bacteriol 186:2281–2287. https://doi.org/10.1128/JB.186.8.2281-2287.2004 CrossRefPubMedPubMedCentral

10.

Pacheco AR, Sperandio V (2009) Inter-kingdom signaling: chemical language between bacteria and host. Curr Opin Microbiol 12:192–198. https://doi.org/10.1016/j.mib.2009.01.006 CrossRefPubMedPubMedCentral

11.

Davis BM, Jensen R, Williams P, O’Shea P (2010) The interaction of N-Acylhomoserine lactone quorum sensing signaling molecules with biological membranes: implications for inter-kingdom signaling. PLoS ONE 5:e13522. https://doi.org/10.1371/journal.pone.0013522 CrossRefPubMedPubMedCentral

12.

Smith RS, Fedyk ER, Springer TA et al (2001) IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF- B and activator protein-2. J Immunol 167:366–374. https://doi.org/10.4049/jimmunol.167.1.366 CrossRefPubMed

13.

Jahoor A, Patel R, Bryan A et al (2008) Peroxisome proliferator-activated receptors mediate host cell proinflammatory responses to Pseudomonas aeruginosa autoinducer. J Bacteriol 190:4408–4415. https://doi.org/10.1128/JB.01444-07 CrossRefPubMedPubMedCentral

14.

Kravchenko VV, Kaufmann GF, Mathison JC et al (2008) Modulation of gene expression via disruption of NF-kappab signaling by a bacterial small molecule. Science 80(321):259–263. https://doi.org/10.1126/science.1156499 CrossRef

15.

Kravchenko VV, Kaufmann GF, Mathison JC et al (2006) N -(3-Oxo-acyl)homoserine lactones signal cell activation through a mechanism distinct from the canonical pathogen-associated molecular pattern recognition receptor pathways. J Biol Chem 281:28822–28830. https://doi.org/10.1074/jbc.M606613200 CrossRefPubMed

16.

Hooi DSW, Bycroft BW, Chhabra SR et al (2004) differential immune modulatory activity of Pseudomonas aeruginosa quorum-sensing signal molecules. Infect Immun 72:6463–6470. https://doi.org/10.1128/IAI.72.11.6463-6470.2004 CrossRefPubMedPubMedCentral

17.

Yadav VK, Singh PK, Kalia M et al (2018) Pseudomonas aeruginosa quorum sensing molecule N-3-oxo-dodecanoyl-l-homoserine lactone activates human platelets through intracellular calcium-mediated ROS generation. Int J Med Microbiol 308:858–864. https://doi.org/10.1016/j.ijmm.2018.07.009 CrossRefPubMed

18.

Karlsson T, Musse F, Magnusson K-E, Vikström E (2012) N -Acylhomoserine lactones are potent neutrophil chemoattractants that act via calcium mobilization and actin remodeling. J Leukoc Biol 91:15–26. https://doi.org/10.1189/jlb.0111034 CrossRefPubMed

19.

Vikström E, Tafazoli F, Magnusson K-E (2006) Pseudomonas aeruginosa quorum sensing molecule N -(3 oxododecanoyl)- l -homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells. FEBS Lett 580:6921–6928. https://doi.org/10.1016/j.febslet.2006.11.057 CrossRefPubMed

20.

Vikström E, Bui L, Konradsson P, Magnusson K-E (2010) Role of calcium signalling and phosphorylations in disruption of the epithelial junctions by Pseudomonas aeruginosa quorum sensing molecule. Eur J Cell Biol 89:584–597. https://doi.org/10.1016/j.ejcb.2010.03.002 CrossRefPubMed

21.

Li H, Wang L, Ye L et al (2009) Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells. Med Microbiol Immunol 198:113–121. https://doi.org/10.1007/s00430-009-0111-z CrossRefPubMed

22.

Schwarzer C, Fu Z, Patanwala M et al (2012) Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia. Cell Microbiol 14:698–709. https://doi.org/10.1111/j.1462-5822.2012.01753.x CrossRefPubMedPubMedCentral

23.

Schwarzer C, Ravishankar B, Patanwala M et al (2014) Thapsigargin blocks Pseudomonas aeruginosa homoserine lactone-induced apoptosis in airway epithelia. Am J Physiol Physiol 306:C844–C855. https://doi.org/10.1152/ajpcell.00002.2014 CrossRef

24.

Shiner EK, Terentyev D, Bryan A et al (2006) Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling. Cell Microbiol 8:1601–1610. https://doi.org/10.1111/j.1462-5822.2006.00734.x CrossRefPubMed

25.

Tateda K, Ishii Y, Horikawa M et al (2003) The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Infect Immun 71:5785–5793CrossRef

26.

Witko-Sarsat V, Pederzoli-Ribeil M, Hirsh E et al (2011) Regulating neutrophil apoptosis: new players enter the game. Trends Immunol 32:117–124. https://doi.org/10.1016/j.it.2011.01.001 CrossRefPubMed

27.

Martin N, Bernard D (2018) Calcium signaling and cellular senescence. Cell Calcium 70:16–23. https://doi.org/10.1016/j.ceca.2017.04.001 CrossRefPubMed

28.

Cao A, Li Q, Yin P et al (2013) Curcumin induces apoptosis in human gastric carcinoma AGS cells and colon carcinoma HT-29 cells through mitochondrial dysfunction and endoplasmic reticulum stress. Apoptosis 18:1391–1402. https://doi.org/10.1007/s10495-013-0871-1 CrossRefPubMed

29.

Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium–apoptosis link. Nat Rev Mol Cell Biol 4:552–565. https://doi.org/10.1038/nrm1150 CrossRef

30.

Hajnóczky G, Csordás G, Das S et al (2006) Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2 + uptake in apoptosis. Cell Calcium 40:553–560. https://doi.org/10.1016/j.ceca.2006.08.016 CrossRefPubMedPubMedCentral

31.

Schwarzer C, Fu Z, Morita T et al (2015) Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N -(3-Oxododecanoyl)-homoserine lactone. J Biol Chem 290:7247–7258. https://doi.org/10.1074/jbc.M114.620039 CrossRefPubMedPubMedCentral

32.

Shahzad T, Kasseckert SA, Iraqi W et al (2013) Mechanisms involved in postconditioning protection of cardiomyocytes against acute reperfusion injury. J Mol Cell Cardiol 58:209–216. https://doi.org/10.1016/j.yjmcc.2013.01.003 CrossRefPubMed

33.

Zhao Z, Gordan R, Wen H et al (2013) Modulation of intracellular calcium waves and triggered activities by mitochondrial Ca flux in mouse cardiomyocytes. PLoS ONE 8:e80574. https://doi.org/10.1371/journal.pone.0080574 CrossRefPubMedPubMedCentral

34.

Sedova M, Blatter LA (2000) Intracellular sodium modulates mitochondrial calcium signaling in vascular endothelial cells. J Biol Chem 275:35402–35407. https://doi.org/10.1074/jbc.M006058200 CrossRefPubMed

35.

Williams P, Cámara M (2009) Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol 12:182–191. https://doi.org/10.1016/j.mib.2009.01.005 CrossRefPubMed

36.

Singh PK, Yadav VK, Kalia M et al (2017) Pseudomonas aeruginosa auto inducer 3-oxo-C 12 -HSL exerts bacteriostatic effect and inhibits Staphylococcus epidermidis biofilm. Microb Pathog 110:612–619. https://doi.org/10.1016/j.micpath.2017.08.009 CrossRefPubMed

37.

Qazi S, Middleton B, Muharram SH et al (2006) N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing in Staphylococcus aureus. Infect Immun 74:910–919. https://doi.org/10.1128/IAI.74.2.910-919.2006 CrossRefPubMedPubMedCentral

38.

Sun Y, Karmakar M, Taylor PR et al (2012) ExoS and ExoT ADP ribosyltransferase activities mediate Pseudomonas aeruginosa keratitis by promoting neutrophil apoptosis and bacterial survival. J Immunol 188:1884–1895. https://doi.org/10.4049/jimmunol.1102148 CrossRefPubMedPubMedCentral

39.

Usher LR, Lawson RA, Geary I et al (2002) Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection. J Immunol 168:1861–1868. https://doi.org/10.4049/jimmunol.168.4.1861 CrossRefPubMed

40.

Allen L, Dockrell DH, Pattery T et al (2005) Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo. J Immunol 174:3643–3649. https://doi.org/10.4049/jimmunol.174.6.3643 CrossRefPubMed

41.

Singh PK, Schaefer AL, Parsek MR et al (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407:762–764. https://doi.org/10.1038/35037627 CrossRefPubMed

42.

Erickson DL (2002) Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect Immun 70:1783–1790. https://doi.org/10.1128/IAI.70.4.1783-1790.2002 CrossRefPubMedPubMedCentral

43.

Miyairi S (2006) Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection. J Med Microbiol 55:1381–1387. https://doi.org/10.1099/jmm.0.46658-0 CrossRefPubMed

44.

Pearson JP, Gray KM, Passador L et al (1994) Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc Natl Acad Sci 91:197–201. https://doi.org/10.1073/pnas.91.1.197 CrossRefPubMed

45.

Teplitski M, Mathesius U, Rumbaugh KP (2011) Perception and degradation of N-Acyl homoserine lactone quorum sensing signals by mammalian and plant cells. Chem Rev 111:100–116. https://doi.org/10.1021/cr100045m CrossRefPubMed

46.

Charlton TS, de Nys R, Netting A et al (2000) A novel and sensitive method for the quantification of N -3-oxoacyl homoserine lactones using gas chromatography-mass spectrometry: application to a model bacterial biofilm. Environ Microbiol 2:530–541. https://doi.org/10.1046/j.1462-2920.2000.00136.x CrossRefPubMed

47.

Chambers CE, Visser MB, Schwab U, Sokol PA (2005) Identification of N -acylhomoserine lactones in mucopurulent respiratory secretions from cystic fibrosis patients. FEMS Microbiol Lett 244:297–304. https://doi.org/10.1016/j.femsle.2005.01.055 CrossRefPubMed

48.

Teiber JF, Horke S, Haines DC et al (2008) Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa quorum-sensing signal N-(3-Oxododecanoyl)-L-homoserine lactone. Infect Immun 76:2512–2519. https://doi.org/10.1128/IAI.01606-07 CrossRefPubMedPubMedCentral

49.

Yang F, Wang L-H, Wang J et al (2005) Quorum quenching enzyme activity is widely conserved in the sera of mammalian species. FEBS Lett 579:3713–3717. https://doi.org/10.1016/j.febslet.2005.05.060 CrossRefPubMed

50.

Tao S, Luo Y, He Bin et al (2016) Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone. Sci Rep 6:28778. https://doi.org/10.1038/srep28778 CrossRefPubMedPubMedCentral

51.

Smith RS, Kelly R, Iglewski BH, Phipps RP (2002) The Pseudomonas autoinducer N-(3-Oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation. J Immunol 169:2636–2642. https://doi.org/10.4049/jimmunol.169.5.2636 CrossRefPubMed

52.

Smith RS, Harris SG, Phipps R, Iglewski B (2002) The Pseudomonas aeruginosa quorum-sensing molecule N-(3-Oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 184:1132–1139. https://doi.org/10.1128/jb.184.4.1132-1139.2002 CrossRefPubMedPubMedCentral

53.

La Rovere RML, Roest G, Bultynck G, Parys JB (2016) Intracellular Ca(2 +) signaling and Ca(2 +) microdomains in the control of cell survival, apoptosis and autophagy. Cell Calcium 60:74–87. https://doi.org/10.1016/j.ceca.2016.04.005 CrossRefPubMed

54.

Lee M-J, Kee K-H, Suh C-H et al (2009) Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways. Toxicology 264:205–214. https://doi.org/10.1016/j.tox.2009.08.012 CrossRefPubMed

55.

Bagur R, Hajnóczky G (2017) Intracellular Ca 2 + sensing: its role in calcium homeostasis and signaling. Mol Cell 66:780–788. https://doi.org/10.1016/j.molcel.2017.05.028 CrossRefPubMedPubMedCentral

56.

Krebs J, Agellon LB, Michalak M (2015) Ca2 + homeostasis and endoplasmic reticulum (ER) stress: an integrated view of calcium signaling. Biochem Biophys Res Commun 460:114–121. https://doi.org/10.1016/j.bbrc.2015.02.004 CrossRefPubMed

57.

Bootman MD, Collins TJ, Mackenzie L et al (2002) 2-aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2 + entry but an inconsistent inhibitor of InsP3-induced Ca2 + release. FASEB J 16:1145–1150. https://doi.org/10.1096/fj.02-0037rev CrossRefPubMed

58.

Yuan Z, Cao A, Liu H et al (2017) Calcium uptake via mitochondrial uniporter contributes to palmitic acid-induced apoptosis in mouse podocytes. J Cell Biochem 118:2809–2818. https://doi.org/10.1002/jcb.25930 CrossRefPubMed

59.

Rapizzi E, Pinton P, Szabadkai G et al (2002) Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca 2 + microdomains to mitochondria. J Cell Biol 159:613–624. https://doi.org/10.1083/jcb.200205091 CrossRefPubMedPubMedCentral

60.

Kirichok Y, Krapivinsky G, Clapham DE (2004) The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427:360–364. https://doi.org/10.1038/nature02246 CrossRefPubMed

61.

Baumgartner HK, Gerasimenko JV, Thorne C et al (2009) Calcium elevation in mitochondria is the main Ca 2 + requirement for mitochondrial permeability transition pore (mPTP) opening. J Biol Chem 284:20796–20803. https://doi.org/10.1074/jbc.M109.025353 CrossRefPubMedPubMedCentral

62.

Adam-Vizi V, Starkov AA (2010) Calcium and mitochondrial reactive oxygen species generation: how to read the facts. J Alzheimer’s Dis 20:S413–S426. https://doi.org/10.3233/JAD-2010-100465 CrossRef

63.

Rizvi F, Heimann T, Herrnreiter A, O’Brien WJ (2011) Mitochondrial dysfunction links ceramide activated HRK expression and cell death. PLoS ONE 6:e18137. https://doi.org/10.1371/journal.pone.0018137 CrossRefPubMedPubMedCentral

64.

Hoppe UC (2010) Mitochondrial calcium channels. FEBS Lett 584:1975–1981. https://doi.org/10.1016/j.febslet.2010.04.017 CrossRef

Titel: Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-l-homoserine lactone triggers mitochondrial dysfunction and apoptosis in neutrophils through calcium signaling
verfasst von: Pradeep Kumar Singh
Vivek Kumar Yadav
Manmohit Kalia
Deepmala Sharma
Deepak Pandey
Vishnu Agarwal
Publikationsdatum: 03.08.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Medical Microbiology and Immunology / Ausgabe 6/2019
Print ISSN: 0300-8584
Elektronische ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-019-00631-8

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