[논문]MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus

Kim, Byoung Sik; Kim, Jong-Hwan; Choi, Sanghyeon; Park, Shinhye; Lee, Eun-Young; Koh, Serry; Ryu, Choong-Min; Kim, Seon-Young; Kim, Myung Hee; D'Orazio, Sarah E. F.

doi:10.1128/mSphere.00659-20

[해외논문] MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus 원문보기

MSphere, v.5 no.4, 2020년, pp.e00659-20 - e00659-20

Kim, Byoung Sik (Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea) , Kim, Jong-Hwan (Department of Functional Genomics, University of Science and Technology, Daejeon, South Korea) , Choi, Sanghyeon (Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea) , Park, Shinhye (Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea) , Lee, Eun-Young (Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea) , Koh, Serry (Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea) , Ryu, Choong-Min (Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnol) , Kim, Seon-Young , Kim, Myung Hee , D'Orazio, Sarah E. F.

Abstract ▼ AI-Helper

V. vulnificus is an opportunistic human pathogen that can cause life-threatening sepsis in immunocompromised patients via seafood poisoning or wound infection. Among the toxic substances produced by this pathogen, the MARTX toxin greatly contributes to disease progression by promoting the dysfunction and death of host cells, which allows the bacteria to disseminate and colonize the host. In response to this, host cells mount a counterattack against the invaders by upregulating various defense genes. In this study, the gene expression profiles of both host cells and V. vulnificus were analyzed by RNA sequencing to gain a comprehensive understanding of host-pathogen interactions. Our results suggest that V. vulnificus uses the MARTX toxin to subvert host cell immune responses as well as to oppose host counterattacks such as iron limitation.ABSTRACTTo understand toxin-stimulated host-pathogen interactions, we performed dual-transcriptome sequencing experiments using human epithelial (HT-29) and differentiated THP-1 (dTHP-1) immune cells infected with the sepsis-causing pathogen Vibrio vulnificus (either the wild-type [WT] pathogen or a multifunctional-autoprocessing repeats-in-toxin [MARTX] toxin-deficient strain). Gene set enrichment analyses revealed MARTX toxin-dependent responses, including negative regulation of extracellular related kinase 1 (ERK1) and ERK2 (ERK1/2) signaling and cell cycle regulation in HT-29 and dTHP-1 cells, respectively. Further analysis of the expression of immune-related genes suggested that the MARTX toxin dampens immune responses in gut epithelial cells but accelerates inflammation and nuclear factor κB (NF-κB) signaling in immune cells. With respect to the pathogen, siderophore biosynthesis genes were significantly more highly expressed in WT V. vulnificus than in the MARTX toxin-deficient mutant upon infection of dTHP-1 cells. Consistent with these results, iron homeostasis genes that limit iron levels for invading pathogens were overexpressed in WT V. vulnificus-infected dTHP-1 cells. Taken together, these results suggest that MARTX toxin regulates host inflammatory responses during V. vulnificus infection while also countering host defense mechanisms such as iron limitation.IMPORTANCE V. vulnificus is an opportunistic human pathogen that can cause life-threatening sepsis in immunocompromised patients via seafood poisoning or wound infection. Among the toxic substances produced by this pathogen, the MARTX toxin greatly contributes to disease progression by promoting the dysfunction and death of host cells, which allows the bacteria to disseminate and colonize the host. In response to this, host cells mount a counterattack against the invaders by upregulating various defense genes. In this study, the gene expression profiles of both host cells and V. vulnificus were analyzed by RNA sequencing to gain a comprehensive understanding of host-pathogen interactions. Our results suggest that V. vulnificus uses the MARTX toxin to subvert host cell immune responses as well as to oppose host counterattacks such as iron limitation.

Keyword

참고문헌 (79)

1. do Vale A , Cabanes D , Sousa S . 2016 . Bacterial toxins as pathogen weapons against phagocytes . Front Microbiol 7 : 42 . doi: 10.3389/fmicb.2016.00042 . 26870008

상세보기
2. Bhavsar AP , Guttman JA , Finlay BB . 2007 . Manipulation of host-cell pathways by bacterial pathogens . Nature 449 : 827 – 834 . doi: 10.1038/nature06247 . 17943119

상세보기
3. Jenner RG , Young RA . 2005 . Insights into host responses against pathogens from transcriptional profiling . Nat Rev Microbiol 3 : 281 – 294 . doi: 10.1038/nrmicro1126 . 15806094

상세보기
4. Chattopadhyay PK , Roederer M , Bolton DL . 2018 . A deadly dance: the choreography of host–pathogen interactions, as revealed by single-cell technologies . Nat Commun 9 : 4638 . doi: 10.1038/s41467-018-06214-0 . 30401874

상세보기
5. Wang Z , Gerstein M , Snyder M . 2009 . RNA-Seq: a revolutionary tool for transcriptomics . Nat Rev Genet 10 : 57 – 63 . doi: 10.1038/nrg2484 . 19015660

상세보기
6. Marioni JC , Mason CE , Mane SM , Stephens M , Gilad Y . 2008 . RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays . Genome Res 18 : 1509 – 1517 . doi: 10.1101/gr.079558.108 . 18550803

상세보기
7. Stark R , Grzelak M , Hadfield J . 2019 . RNA sequencing: the teenage years . Nat Rev Genet 20 : 631 – 656 . doi: 10.1038/s41576-019-0150-2 . 31341269

상세보기
8. Westermann AJ , Gorski SA , Vogel J . 2012 . Dual RNA-seq of pathogen and host . Nat Rev Microbiol 10 : 618 – 630 . doi: 10.1038/nrmicro2852 . 22890146

상세보기
9. Westermann AJ , Förstner KU , Amman F , Barquist L , Chao Y , Schulte LN , Müller L , Reinhardt R , Stadler PF , Vogel J . 2016 . Dual RNA-seq unveils noncoding RNA functions in host–pathogen interactions . Nature 529 : 496 – 501 . doi: 10.1038/nature16547 . 26789254

상세보기
10. Aprianto R , Slager J , Holsappel S , Veening J-W . 2016 . Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection . Genome Biol 17 : 198 . doi: 10.1186/s13059-016-1054-5 . 27678244

상세보기
11. Damron FH , Oglesby-Sherrouse AG , Wilks A , Barbier M . 2016 . Dual-seq transcriptomics reveals the battle for iron during Pseudomonas aeruginosa acute murine pneumonia . Sci Rep 6 : 39172 . doi: 10.1038/srep39172 . 27982111

상세보기
12. Baker-Austin C , Oliver JD , Alam M , Ali A , Waldor MK , Qadri F , Martinez-Urtaza J . 2018 . Vibrio spp. infections . Nat Rev Dis Primers 4 : 8 . doi: 10.1038/s41572-018-0005-8 . 30002421

상세보기
13. Baker-Austin C , Oliver JD . 2018 . Vibrio vulnificus : new insights into a deadly opportunistic pathogen . Environ Microbiol 20 : 423 – 430 . doi: 10.1111/1462-2920.13955 . 29027375

상세보기
14. Jeong HG , Satchell KJ . 2012 . Additive function of Vibrio vulnificus MARTX(Vv) and VvhA cytolysins promotes rapid growth and epithelial tissue necrosis during intestinal infection . PLoS Pathog 8 : e1002581 . doi: 10.1371/journal.ppat.1002581 . 22457618

상세보기
15. Lee JH , Kim MW , Kim BS , Kim SM , Lee BC , Kim TS , Choi SH . 2007 . Identification and characterization of the Vibrio vulnificus rtxA essential for cytotoxicity in vitro and virulence in mice . J Microbiol 45 : 146 – 152 . 17483800

원문보기 상세보기
16. Liu M , Alice AF , Naka H , Crosa JH . 2007 . The HlyU protein is a positive regulator of rtxA1 , a gene responsible for cytotoxicity and virulence in the human pathogen Vibrio vulnificus . Infect Immun 75 : 3282 – 3289 . doi: 10.1128/IAI.00045-07 . 17438022

상세보기
17. Kim YR , Lee SE , Kook H , Yeom JA , Na HS , Kim SY , Chung SS , Choy HE , Rhee JH . 2008 . Vibrio vulnificus RTX toxin kills host cells only after contact of the bacteria with host cells . Cell Microbiol 10 : 848 – 862 . doi: 10.1111/j.1462-5822.2007.01088.x . 18005241

상세보기
18. Lee CT , Pajuelo D , Llorens A , Chen YH , Leiro JM , Padros F , Hor LI , Amaro C . 2013 . MARTX of Vibrio vulnificus biotype 2 is a virulence and survival factor . Environ Microbiol 15 : 419 – 432 . doi: 10.1111/j.1462-2920.2012.02854.x . 22943291

상세보기
19. Ziolo KJ , Jeong HG , Kwak JS , Yang S , Lavker RM , Satchell KJ . 2014 . Vibrio vulnificus biotype 3 multifunctional autoprocessing RTX toxin is an adenylate cyclase toxin essential for virulence in mice . Infect Immun 82 : 2148 – 2157 . doi: 10.1128/IAI.00017-14 . 24614656

상세보기
20. Satchell KJ . 2007 . MARTX, multifunctional autoprocessing repeats-in-toxin toxins . Infect Immun 75 : 5079 – 5084 . doi: 10.1128/IAI.00525-07 . 17646359

상세보기
21. Satchell KJF . 2015 . Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of Vibrios . Microbiol Spectr 3 ( 3 ). doi: 10.1128/microbiolspec.VE-0002-2014 .

상세보기
22. Kim BS . 2018 . The modes of action of MARTX toxin effector domains . Toxins (Basel) 10 : 507 . doi: 10.3390/toxins10120507 .

상세보기
23. Woida PJ , Satchell KJF . 2018 . Coordinated delivery and function of bacterial MARTX toxin effectors . Mol Microbiol 107 : 133 – 141 . doi: 10.1111/mmi.13875 . 29114985

상세보기
24. Lee Y , Kim BS , Choi S , Lee E-Y , Park S , Hwang J , Kwon Y , Hyun J , Lee C , Kim JF , Eom SH , Kim MH . 2019 . Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity . Proc Natl Acad Sci U S A 116 : 18031 – 18040 . doi: 10.1073/pnas.1905095116 . 31427506

상세보기
25. Zhou Y , Huang C , Yin L , Wan M , Wang X , Li L , Liu Y , Wang Z , Fu P , Zhang N , Chen S , Liu X , Shao F , Zhu Y . 2017 . N(epsilon)-Fatty acylation of Rho GTPases by a MARTX toxin effector . Science 358 : 528 – 531 . doi: 10.1126/science.aam8659 . 29074776

상세보기
26. Sheahan KL , Satchell KJ . 2007 . Inactivation of small Rho GTPases by the multifunctional RTX toxin from Vibrio cholerae . Cell Microbiol 9 : 1324 – 1335 . doi: 10.1111/j.1462-5822.2006.00876.x . 17474905

상세보기
27. Biancucci M , Minasov G , Banerjee A , Herrera A , Woida PJ , Kieffer MB , Bindu L , Abreu-Blanco M , Anderson WF , Gaponenko V , Stephen AG , Holderfield M , Satchell KJF . 2018 . The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling . Sci Signal 11 : eaat8335 . doi: 10.1126/scisignal.aat8335 . 30279169

상세보기
28. Jang SY , Hwang J , Kim BS , Lee EY , Oh BH , Kim MH . 2018 . Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogen Vibrio vulnificus . J Biol Chem 293 : 18110 – 18122 . doi: 10.1074/jbc.RA118.004857 . 30282804

상세보기
29. Kim BS , Gavin HE , Satchell KJ . 2015 . Distinct roles of the repeat-containing regions and effector domains of the Vibrio vulnificus multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin . mBio 6 : e00324-15 . doi: 10.1128/mBio.00324-15 . 25827415

상세보기
30. Callol A , Reyes-Lopez FE , Roig FJ , Goetz G , Goetz FW , Amaro C , MacKenzie SA . 2015 . An enriched European eel transcriptome sheds light upon host-pathogen interactions with Vibrio vulnificus . PLoS One 10 : e0133328 . doi: 10.1371/journal.pone.0133328 . 26207370

상세보기
31. Murciano C , Lee CT , Fernandez-Bravo A , Hsieh TH , Fouz B , Hor LI , Amaro C . 2017 . MARTX toxin in the zoonotic serovar of Vibrio vulnificus triggers an early cytokine storm in mice . Front Cell Infect Microbiol 7 : 332 . doi: 10.3389/fcimb.2017.00332 . 28775962

상세보기
32. Lee A , Kim MS , Cho D , Jang KK , Choi SH , Kim TS . 2018 . Vibrio vulnificus RtxA is a major factor driving inflammatory T helper type 17 cell responses in vitro and in vivo . Front Immunol 9 : 332 . doi: 10.3389/fimmu.2018.02095 . 29535720

상세보기
33. Liu Y , Zhou J , White KP . 2014 . RNA-seq differential expression studies: more sequence or more replication? Bioinformatics 30 : 301 – 304 . doi: 10.1093/bioinformatics/btt688 . 24319002

상세보기
34. Huang DW , Sherman BT , Lempicki RA . 2009 . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources . Nat Protoc 4 : 44 – 57 . doi: 10.1038/nprot.2008.211 . 19131956

상세보기
35. Huang DW , Sherman BT , Lempicki RA . 2009 . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists . Nucleic Acids Res 37 : 1 – 13 . doi: 10.1093/nar/gkn923 . 19033363

상세보기
36. Agarwal S , Kim H , Chan RB , Agarwal S , Williamson R , Cho W , Paolo GD , Paolo GD , Satchell KJF . 2015 . Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity . Nat Commun 6 : 8745 . doi: 10.1038/ncomms9745 . 26498860

상세보기
37. Antic I , Biancucci M , Zhu Y , Gius DR , Satchell KJ . 2015 . Site-specific processing of Ras and Rap1 Switch I by a MARTX toxin effector domain . Nat Commun 6 : 7396 . doi: 10.1038/ncomms8396 . 26051945

상세보기
38. Combes G , Alharbi I , Braga LG , Elowe S . 2017 . Playing polo during mitosis: PLK1 takes the lead . Oncogene 36 : 4819 – 4827 . doi: 10.1038/onc.2017.113 . 28436952

상세보기
39. Kim BA , Lim JY , Rhee JH , Kim YR . 2016 . Characterization of prohibitin 1 as a host partner of Vibrio vulnificus RtxA1 toxin . J Infect Dis 213 : 131 – 138 . doi: 10.1093/infdis/jiv362 . 26136468

상세보기
40. Peng Y-T , Chen P , Ouyang R-Y , Song L . 2015 . Multifaceted role of prohibitin in cell survival and apoptosis . Apoptosis 20 : 1135 – 1149 . doi: 10.1007/s10495-015-1143-z . 26091791

상세보기
41. De Nisco NJ , Kanchwala M , Li P , Fernandez J , Xing C , Orth K . 2017 . The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to subvert cell death and activate cell survival pathways . Sci Signal 10 : eaal4501 . doi: 10.1126/scisignal.aal4501 . 28512145

상세보기
42. De Filippo K , Rankin SM . 2018 . CXCR4, the master regulator of neutrophil trafficking in homeostasis and disease . Eur J Clin Invest 48 : e12949 . doi: 10.1111/eci.12949 . 29734477

상세보기
43. Ronchetti S , Migliorati G , Riccardi C . 2015 . GILZ as a mediator of the anti-inflammatory effects of glucocorticoids . Front Endocrinol (Lausanne) 6 : 170 . doi: 10.3389/fendo.2015.00170 . 26617572

상세보기
44. Berrebi D , Bruscoli S , Cohen N , Foussat A , Migliorati G , Bouchet-Delbos L , Maillot M-C , Portier A , Couderc J , Galanaud P , Peuchmaur M , Riccardi C , Emilie D . 2003 . Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10 . Blood 101 : 729 – 738 . doi: 10.1182/blood-2002-02-0538 . 12393603

상세보기
45. Applequist SE , Wallin RPA , Ljunggren HG . 2002 . Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines . Int Immunol 14 : 1065 – 1074 . doi: 10.1093/intimm/dxf069 . 12202403

상세보기
46. Abreu MT . 2010 . Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function . Nat Rev Immunol 10 : 131 – 144 . doi: 10.1038/nri2707 . 20098461

상세보기
47. Kim S-Y , Volsky DJ . 2005 . PAGE: parametric analysis of gene set enrichment . BMC Bioinformatics 6 : 144 . doi: 10.1186/1471-2105-6-144 . 15941488

상세보기
48. Kanehisa M , Goto S . 2000 . KEGG: Kyoto Encyclopedia of Genes and Genomes . Nucleic Acids Res 28 : 27 – 30 . doi: 10.1093/nar/28.1.27 . 10592173

상세보기
49. Duong-Nu T-M , Jeong K , Hong SH , Puth S , Kim SY , Tan W , Lee KH , Lee SE , Rhee JH . 2019 . A stealth adhesion factor contributes to Vibrio vulnificus pathogenicity: Flp pili play roles in host invasion, survival in the blood stream and resistance to complement activation . PLoS Pathog 15 : e1007767 . doi: 10.1371/journal.ppat.1007767 . 31437245

상세보기
50. Aagesen AM , Häse CC . 2012 . Sequence analyses of type IV pili from Vibrio cholerae , Vibrio parahaemolyticus , and Vibrio vulnificus . Microb Ecol 64 : 509 – 524 . doi: 10.1007/s00248-012-0021-2 . 22383120

상세보기
51. Williams TC , Ayrapetyan M , Oliver JD . 2014 . Implications of chitin attachment for the environmental persistence and clinical nature of the human pathogen Vibrio vulnificus . Appl Environ Microbiol 80 : 1580 – 1587 . doi: 10.1128/AEM.03811-13 . 24362430

상세보기
52. Gohara DW , Yap M-NF . 2018 . Survival of the drowsiest: the hibernating 100S ribosome in bacterial stress management . Curr Genet 64 : 753 – 760 . doi: 10.1007/s00294-017-0796-2 . 29243175

상세보기
53. Kvint K , Nachin L , Diez A , Nyström T . 2003 . The bacterial universal stress protein: function and regulation . Curr Opin Microbiol 6 : 140 – 145 . doi: 10.1016/s1369-5274(03)00025-0 . 12732303

상세보기
54. Ennis HL , Kievitt KD , Artman M . 1974 . Synthesis of β-galactosidase messenger RNA during amino acid starvation of stringent and relaxed strains of Escherichia coli . Biochem Biophys Res Commun 59 : 429 – 436 . doi: 10.1016/s0006-291x(74)80224-x . 4601818

상세보기
55. Choi HK , Park NY , Kim D-i , Chung HJ , Ryu S , Choi SH . 2002 . Promoter analysis and regulatory characteristics of vvhBA encoding cytolytic hemolysin of Vibrio vulnificus . J Biol Chem 277 : 47292 – 47299 . doi: 10.1074/jbc.M206893200 . 12356775

상세보기
56. Lee H-J , Kim J-A , Lee M-A , Park S-J , Lee K-H . 2013 . Regulation of haemolysin (VvhA) production by ferric uptake regulator (Fur) in Vibrio vulnificus : repression of vvhA transcription by Fur and proteolysis of VvhA by Fur-repressive exoproteases . Mol Microbiol 88 : 813 – 826 . doi: 10.1111/mmi.12224 . 23560801

상세보기
57. Shao CP , Lo HR , Lin JH , Hor LI . 2011 . Regulation of cytotoxicity by quorum-sensing signaling in Vibrio vulnificus is mediated by SmcR, a repressor of hlyU . J Bacteriol 193 : 2557 – 2565 . doi: 10.1128/JB.01259-10 . 21398530

상세보기
58. Elgaml A , Miyoshi S-I . 2015 . Role of the histone-like nucleoid structuring protein (H-NS) in the regulation of virulence factor expression and stress response in Vibrio vulnificus . Biocontrol Sci 20 : 263 – 274 . doi: 10.4265/bio.20.263 . 26699858

상세보기
59. Litwin CM , Rayback TW , Skinner J . 1996 . Role of catechol siderophore synthesis in Vibrio vulnificus virulence . Infect Immun 64 : 2834 – 2838 . doi: 10.1128/IAI.64.7.2834-2838.1996 . 8698519

상세보기
60. Tan W , Verma V , Jeong K , Kim S , Jung C-H , Lee S , Rhee J . 2014 . Molecular characterization of vulnibactin biosynthesis in Vibrio vulnificus indicates the existence of an alternative siderophore . Front Microbiol 5 : 1 . doi: 10.3389/fmicb.2014.00001 . 24478763

상세보기
61. Lee BC , Lee JH , Kim MW , Kim BS , Oh MH , Kim KS , Kim TS , Choi SH . 2008 . Vibrio vulnificus rtxE is important for virulence, and its expression is induced by exposure to host cells . Infect Immun 76 : 1509 – 1517 . doi: 10.1128/IAI.01503-07 . 18250174

상세보기
62. Parrow NL , Fleming RE , Minnick MF . 2013 . Sequestration and scavenging of iron in infection . Infect Immun 81 : 3503 – 3514 . doi: 10.1128/IAI.00602-13 . 23836822

상세보기
63. Ganz T , Nemeth E . 2015 . Iron homeostasis in host defence and inflammation . Nat Rev Immunol 15 : 500 – 510 . doi: 10.1038/nri3863 . 26160612

상세보기
64. Arezes J , Jung G , Gabayan V , Valore E , Ruchala P , Gulig PA , Ganz T , Nemeth E , Bulut Y . 2015 . Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus . Cell Host Microbe 17 : 47 – 57 . doi: 10.1016/j.chom.2014.12.001 . 25590758

상세보기
65. O'Grady E , Mulcahy H , Adams C , Morrissey JP , O'Gara F . 2007 . Manipulation of host Kruppel-like factor (KLF) function by exotoxins from diverse bacterial pathogens . Nat Rev Microbiol 5 : 337 – 341 . doi: 10.1038/nrmicro1641 . 17435789

상세보기
66. Peterson LW , Artis D . 2014 . Intestinal epithelial cells: regulators of barrier function and immune homeostasis . Nat Rev Immunol 14 : 141 – 153 . doi: 10.1038/nri3608 . 24566914

상세보기
67. Kaplan MH . 2005 . STAT4: a critical regulator of inflammation in vivo . Immunol Res 31 : 231 – 241 . doi: 10.1385/IR:31:3:231 . 15888914

상세보기
68. Dorrington MG , Fraser IDC . 2019 . NF-κB signaling in macrophages: dynamics, crosstalk, and signal integration . Front Immunol 10 : 705 . doi: 10.3389/fimmu.2019.00705 . 31024544

상세보기
69. Puthia M , Ambite I , Cafaro C , Butler D , Huang Y , Lutay N , Rydstrom G , Gullstrand B , Swaminathan B , Nadeem A , Nilsson B , Svanborg C . 2016 . IRF7 inhibition prevents destructive innate immunity-A target for nonantibiotic therapy of bacterial infections . Sci Transl Med 8 : 336ra59 . doi: 10.1126/scitranslmed.aaf1156 .

상세보기
70. Freeman BD , Machado FS , Tanowitz HB , Desruisseaux MS . 2014 . Endothelin-1 and its role in the pathogenesis of infectious diseases . Life Sci 118 : 110 – 119 . doi: 10.1016/j.lfs.2014.04.021 . 24780317

상세보기
71. Lo H-R , Lin J-H , Chen Y-H , Chen C-L , Shao C-P , Lai Y-C , Hor L-I . 2011 . RTX toxin enhances the survival of Vibrio vulnificus during infection by protecting the organism from phagocytosis . J Infect Dis 203 : 1866 – 1874 . doi: 10.1093/infdis/jir070 . 21422475

상세보기
72. Chen CL , Chien SC , Leu TH , Harn HI , Tang MJ , Hor LI . 2017 . Vibrio vulnificus MARTX cytotoxin causes inactivation of phagocytosis-related signaling molecules in macrophages . J Biomed Sci 24 : 58 . doi: 10.1186/s12929-017-0368-2 . 28822352

상세보기
73. MacMicking J , Xie QW , Nathan C . 1997 . Nitric oxide and macrophage function . Annu Rev Immunol 15 : 323 – 350 . doi: 10.1146/annurev.immunol.15.1.323 . 9143691

상세보기
74. Westermann AJ , Vogel J . 2018 . Host-pathogen transcriptomics by dual RNA-Seq . Methods Mol Biol 1737 : 59 – 75 . doi: 10.1007/978-1-4939-7634-8_4 . 29484587

상세보기
75. Dobin A , Davis CA , Schlesinger F , Drenkow J , Zaleski C , Jha S , Batut P , Chaisson M , Gingeras TR . 2013 . STAR: ultrafast universal RNA-seq aligner . Bioinformatics 29 : 15 – 21 . doi: 10.1093/bioinformatics/bts635 . 23104886

상세보기
76. Karolchik D , Hinrichs AS , Furey TS , Roskin KM , Sugnet CW , Haussler D , Kent WJ . 2004 . The UCSC Table Browser data retrieval tool . Nucleic Acids Res 32 : D493 – D496 . doi: 10.1093/nar/gkh103 . 14681465

상세보기
77. McCarthy DJ , Chen Y , Smyth GK . 2012 . Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation . Nucleic Acids Res 40 : 4288 – 4297 . doi: 10.1093/nar/gks042 . 22287627

상세보기
78. Luo W , Brouwer C . 2013 . Pathview: an R/Bioconductor package for pathway-based data integration and visualization . Bioinformatics 29 : 1830 – 1831 . doi: 10.1093/bioinformatics/btt285 . 23740750

상세보기
79. Kim IH , Shim JI , Lee KE , Hwang W , Kim IJ , Choi SH , Kim KS . 2008 . Nonribosomal peptide synthase is responsible for the biosynthesis of siderophore in Vibrio vulnificus MO6-24/O . J Microbiol Biotechnol 18 : 35 – 42 . 18239413

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표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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