Inactivation of the antifungal and immunomodulatory properties of human cathelicidin LL-37 by aspartic proteases produced by the pathogenic yeast Candida albicans

Infection and Immunity

Volumn 83, Issue 6, 2015, Pages 2518-2530

  Rapala Kozik, Maria ^a   Bochenska, Oliwia ^a   Zawrotniak, Marcin ^a   Wolak, Natalia ^a   Trebacz, Grzegorz ^a   Gogol, Mariusz ^a   Ostrowska, Dominika ^a   Aoki, Wataru ^b   Ueda, Mitsuyoshi ^c   Kozik, Andrzej ^a  

^a JAGIELLONIAN UNIVERSITY   (Poland)

^b OSAKA UNIVERSITY   (Japan)

^c KYOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC PROTEINASE; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; CYTOCHALASIN D; INTERLEUKIN 8; LIPOPOLYSACCHARIDE; PEPSTATIN; REACTIVE OXYGEN METABOLITE; SAP10 PROTEIN; SAP9 PROTEIN; UNCLASSIFIED DRUG; ANTIFUNGAL AGENT; ANTIMICROBIAL CATIONIC PEPTIDE; CAP18 LIPOPOLYSACCHARIDE-BINDING PROTEIN; CASPASE; CHEMOKINE RECEPTOR CXCR2; IMMUNOLOGIC FACTOR;

AMINO TERMINAL SEQUENCE; ANTIFUNGAL ACTIVITY; APOPTOSIS; ARTICLE; CALCIUM TRANSPORT; CANDIDA ALBICANS; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG DEGRADATION; ELECTROSPRAY MASS SPECTROMETRY; ENZYME ACTIVITY; ENZYME SUBSTRATE; ENZYME TO SUBSTRATE RATIO; EPITHELIUM CELL; FUNGAL STRAIN; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOMODULATION; NEUTROPHIL; NONHUMAN; PH; PHAGOCYTOSIS; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; TANDEM MASS SPECTROMETRY; WILD TYPE; AMINO ACID SEQUENCE; CELL MOTION; COCULTURE; CYTOLOGY; DOSE RESPONSE; DRUG EFFECTS; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PHYSIOLOGY;

AMINO ACID SEQUENCE; ANTIFUNGAL AGENTS; ANTIMICROBIAL CATIONIC PEPTIDES; ASPARTIC ACID PROTEASES; CANDIDA ALBICANS; CASPASES; CELL MOVEMENT; COCULTURE TECHNIQUES; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION; HUMANS; IMMUNOLOGIC FACTORS; NEUTROPHILS; REACTIVE OXYGEN SPECIES; RECEPTORS, INTERLEUKIN-8B;

EID: 84929501304     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.00023-15     Document Type: Article

References (81)

1. Mayer FL, Wilson D, Hube B. 2013. Candida albicans pathogenicity mechanisms. Virulence 4:119-128. http://dx.doi.org/10.4161/viru.22913.
2. Lim CS-Y, Rosli R, Seow HF, Chong PP. 2012. Candida and invasive candidiasis: back to basics. Eur Clin Microbiol Infect Dis 31:21-31. http://dx.doi.org/10.1007/s10096-011-1273-3.
3. Chow JK, Golan Y, Ruthazer R, Karchmer AW, Carmeli Y, Lichtenberg D, Chawla V, Young J, Hadley S. 2008. Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit. Clin Infect Dis 46:1206-1213. http://dx.doi.org/10.1086/529435.
4. Hube B. 2004. From commensal to pathogen: stage-and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol 7:336-341. http://dx.doi.org/10.1016/j.mib.2004.06.003.
5. Mócsai A. 2013. Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med 210:1283-1299. http://dx.doi.org/10.1084/jem.20122220.
6. Brinkmann V, Zychlinsky A. 2007. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 5:577-582. http://dx.doi.org/10.1038/nrmicro1710.
7. Sørensen OE. 2001. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97:3951-3959. http://dx.doi.org/10.1182/blood.V97.12.3951.
8. Kahlenberg JM, Kaplan MJ. 2013. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J Immunol 191:4895-4901. http://dx.doi.org/10.4049/jimmunol.1302005.
9. Bowdish DME, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock REW. 2005. Impact of LL-37 on anti-infective immunity. J Leukoc Biol 77:451-459. http://dx.doi.org/10.1189/jlb.0704380.
10. Lippross S, Klueter T, Steubesand N, Oestern S, Mentlein R, Hildebrandt F, Podschun R, Pufe T, Seekamp A, Varoga D. 2012. Multiple trauma induces serum production of host defence peptides. Injury 43: 137-142. http://dx.doi.org/10.1016/j.injury.2011.03.044.
11. Nijnik A, Hancock R. 2009. Host defence peptides: antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic-resistant infections. Emerg Health Threats J 2:e1. http://dx.doi.org/10.3134/ehtj.09.001.
12. Reinholz M, Ruzicka T, Schauber J. 2012. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann Dermatol 24:126-135. http://dx.doi.org/10.5021/ad.2012.24.2.126.
13. Zhang X, Oglȩêcka K, Sandgren S, Belting M, Esbjörner EK, Nordén B, Gräslund A. 2010. Dual functions of the human antimicrobial peptide LL-37-targetmembraneperturbationandhost cellcargodelivery. BiochimBiophysActa 1798:2201-2208. http://dx.doi.org/10.1016/j.bbamem.2009.12.011.
14. Tsai P-W, Yang C-Y, Chang H-T, Lan C-Y. 2011. Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates. PLoS One 6:e17755. http://dx.doi.org/10.1371/journal.pone.0017755.
15. Ciornei CD, Sigurdardóttir T, Schmidtchen A, Bodelsson M. 2005. Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37. Antimicrob Agents Chemother 49:2845-2850. http://dx.doi.org/10.1128/AAC.49.7.2845-2850.2005.
16. Alalwani SM, Sierigk J, Herr C, Pinkenburg O, Gallo R, Vogelmeier C, Bals R. 2010. The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. Eur J Immunol 40:1118-1126. http://dx.doi.org/10.1002/eji.200939275.
17. Kai-Larsen Y, Agerberth B. 2008. The role of the multifunctional peptide LL-37 in host defense. Front Biosci 13:3760-3767. https://www.bioscience.org/2008/v13/af/2964/fulltext.htm.
18. Nagaoka I, Tamura H, Hirata M. 2006. An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol 176: 3044-3052. http://dx.doi.org/10.4049/jimmunol.176.5.3044.
19. Peschel A, Vincent Collins L. 2001. Staphylococcal resistance to antimicrobial peptides of mammalian and bacterial origin. Peptides 22:1651-1659. http://dx.doi.org/10.1016/S0196-9781(01)00500-9.
20. Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Gotz F. 1999. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274:8405-8410. http://dx.doi.org/10.1074/jbc.274.13.8405.
21. Chakraborty K, Ghosh S, Koley H, Mukhopadhyay AK, Ramamurthy T, Saha DR, Mukhopadhyay D, Roychowdhury S, Hamabata T, Takeda Y, Das S. 2008. Bacterial exotoxins downregulate cathelicidin (hCAP-18/LL-37) and human beta-defensin 1 (HBD-1) expression in the intestinal epithelial cells. Cell Microbiol 10:2520-2537. http://dx.doi.org/10.1111/j.1462-5822.2008.01227.x.
22. Majchrzykiewicz JA, Kuipers OP, Bijlsma JJ. 2010. Generic and specific adaptive responses of Streptococcus pneumoniae to challenge with three distinct antimicrobial peptides, bacitracin, LL-37, and nisin. Antimicrob Agents Chemother 54:440-451. http://dx.doi.org/10.1128/AAC.00769-09.
23. Schmidtchen A, Frick I-M, Andersson E, Tapper H, Björck L. 2002. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46:157-168. http://dx.doi.org/10.1046/j.1365-2958.2002.03146.x.
24. Naglik J, Albrecht A, Bader O, Hube B. 2004. Candida albicans proteinases and host/pathogen interactions. Cell Microbiol 6:915-926. http://dx.doi.org/10.1111/j.1462-5822.2004.00439.x.
25. Aoki W, Kitahara N, Miura N, Morisaka H, Yamamoto Y, Kuroda K, Ueda M. 2011. Comprehensive characterization of secreted aspartic proteases encoded by a virulence gene family in Candida albicans. J Biochem 150:431-438. http://dx.doi.org/10.1093/jb/mvr073.
26. Laemmli UK. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685. http://dx.doi.org/10.1038/227680a0.
27. Blum H, Beier H, Gross HJ. 1987. Improved silver staining of plant proteins, RNA and DNA in polyacrylamide gels. Electrophoresis 8:93-99. http://dx.doi.org/10.1002/elps.1150080203.
28. Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254. http://dx.doi.org/10.1016/0003-2697(76)90527-3.
29. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402-408. http://dx.doi.org/10.1006/meth.2001.1262.
30. Hube B. 2009. Fungal adaptation to the host environment. Curr Opin Microbiol 12:347-349. http://dx.doi.org/10.1016/j.mib.2009.06.009.
31. Hube B, Monod M, Schofield DA, Brown AJ, Gow NA. 1994. Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans. Mol Microbiol 14:87-99. http://dx.doi.org/10.1111/j.1365-2958.1994.tb01269.x.
32. Urban CF, Reichard U, Brinkmann V, Zychlinsky A. 2006. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol 8:668-676. http://dx.doi.org/10.1111/j.1462-5822.2005.00659.x.
33. Braff MH, Hawkins MA, Di Nardo A, Lopez-Garcia B, Howell MD, Wong C, Lin K, Streib JE, Dorschner R, Leung DYM, Gallo RL. 2005. Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities. J Immunol 174:4271-4278. http://dx.doi.org/10.4049/jimmunol.174.7.4271.
34. Barlow PG, Li Y, Wilkinson TS, Bowdish DME, Lau YE, Cosseau C, Haslett C, Simpson AJ, Hancock REW, Davidson DJ. 2006. The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. J Leukoc Biol 80:509-520. http://dx.doi.org/10.1189/jlb.1005560.
35. Zheng Y, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, Ogawa H. 2007. Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br J Dermatol 157:1124-1131. http://dx.doi.org/10.1111/j.1365-2133.2007.08196.x.
36. Zhang Z, Cherryholmes G, Chang F, Rose DM, Schraufstatter I, Shively JE. 2009. Evidence that cathelicidin peptide LL-37 may act as a functional ligand for CXCR2 on human neutrophils. Eur J Immunol 39:3181-3194. http://dx.doi.org/10.1002/eji.200939496.
37. Tjabringa GS, Ninaber DK, Drijfhout JW, Rabe KF, Hiemstra PS. 2006. Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors. Int Arch Allergy Immunol 140:103-112. http://dx.doi.org/10.1159/000092305.
38. Chow LNY, Choi K-YG, Piyadasa H, Bossert M, Uzonna J, Klonisch T, Mookherjee N. 2014. Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis. Mol Immunol 57:86-92. http://dx.doi.org/10.1016/j.molimm.2013.08.011.
39. Duplantier AJ, van Hoek ML. 2013. The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds. Front Immunol 4:143. http://dx.doi.org/10.3389/fimmu.2013.00143.
40. den Hertog AL, van Marle J, van Veen HA, Van't Hof W, Bolsche JGM, Veerman ECI, Nieuw Amerongen AV. 2005. Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. Biochem J 388: 689-695. http://dx.doi.org/10.1042/BJ20042099.
41. den Hertog AL, van Marle J, Veerman ECI, Valentijn-Benz M, Nazmi K, Kalay H, Grün CH, Van't Hof W, Bolscher JGM, Nieuw Amerongen AV. 2006. The human cathelicidin peptide LL-37 and truncated variants induce segregation of lipids and proteins in the plasma membrane of Candida albicans. Biol Chem 387:1495-1502. http://dx.doi.org/10.1515/BC.2006.187.
42. Ordonez SR, Amarullah IH, Wubbolts RW, Veldhuizen EJA, Haagsman HP. 2014. Fungicidal mechanisms of cathelicidins LL-37 and CATH-2 revealed by live-cell imaging. Antimicrob Agents Chemother 58:2240-2248. http://dx.doi.org/10.1128/AAC.01670-13.
43. Tsai P-W, Cheng Y-L, Hsieh W-P, Lan C-Y. 2014. Responses of Candida albicans to the human antimicrobial peptide LL-37. J Microbiol 52:581-589. http://dx.doi.org/10.1007/s12275-014-3630-2.
44. López-García B, Lee PHA, Yamasaki K, Gallo RL. 2005. Anti-fungal activity of cathelicidins and their potential role in Candida albicans skin infection. J Investig Dermatol 125:108-115. http://dx.doi.org/10.1111/j.0022-202X.2005.23713.x.
45. Bergsson G, Reeves EP, McNally P, Chotirmall SH, Greene CM, Greally P, Murphy P, O'Neill SJ, McElvaney NG. 2009. LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline. J Immunol 183:543-551. http://dx.doi.org/10.4049/jimmunol.0803959.
46. Johansson J, Gudmundsson GH, Rottenberg ME, Berndt KD, Agerberth B. 1998. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J Biol Chem 273:3718-3724. http://dx.doi.org/10.1074/jbc.273.6.3718.
47. Sieprawska-Lupa M, Mydel P, Krawczyk K, Wójcik K, Puklo M, Lupa B, Suder P, Silberring J, Reed M, Pohl J, Shafer W, MCAleese I, Foster T, Travis J, Potempa J. 2004. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother 48:4673-4679. http://dx.doi.org/10.1128/AAC.48.12.4673-4679.2004.
48. Koziel J, Karim AY, Przybyszewska K, Ksiazek M, Rapala-Kozik M, Nguyen K-A, Potempa J. 2010. Proteolytic inactivation of LL-37 by karilysin, a novel virulence mechanism of Tannerella forsythia. J Innate Immun 2:288-293. http://dx.doi.org/10.1159/000281881.
49. McCrudden MT, Orr DF, Yu Y, Coulter WA, Manning G, Irwin CR, Lundy FT. 2013. LL-37 in periodontal health and disease and its susceptibility to degradation by proteinases present in gingival crevicular fluid. J Clin Periodontol 40:933-941. http://dx.doi.org/10.1111/jcpe.12141.
50. Naglik JR, Challacombe SJ, Hube B. 2003. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev 67:400-428. http://dx.doi.org/10.1128/MMBR.67.3.400-428.2003.
51. Albrecht A, Felk A, Pichova I, Naglik JR, Schaller M, de Groot P, Maccallum D, Odds FC, Schäfer W, Klis F, Monod M, Hube B. 2006. Glycosylphosphatidylinositol-anchored proteases of Candida albicans target proteins necessary for both cellular processes and host-pathogen interactions. J Biol Chem 281:688-694. http://dx.doi.org/10.1074/jbc.M509297200.
52. Naglik JR, Newport G, White TC, Fernandes-Naglik LL, Greenspan JS, Greenspan D, Sweet SP, Challacombe SJ, Agabian N. 1999. In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis. Infect Immun 67:2482-2490.
53. Naglik JR, Rodgers CA, Shirlaw PJ, Dobbie JL, Fernandes-Naglik LL, Greenspan D, Agabian N, Challacombe SJ. 2003. Differential expression of Candida albicans secreted aspartyl proteinase and phospholipase B genes in humans correlates with active oral and vaginal infections. J Infect Dis 188:469-479. http://dx.doi.org/10.1086/376536.
54. Naglik JR, Moyes D, Makwana J, Kanzaria P, Tsichlaki E, Weindl G, Tappuni AR, Rodgers CA, Woodman AJ, Challacombe SJ, Schaller M, Hube B. 2008. Quantitative expression of the Candida albicans secreted aspartyl proteinase gene family in human oral and vaginal candidiasis. Microbiology 154: 3266-3280. http://dx.doi.org/10.1099/mic.0.2008/022293-0.
55. Schaller M, Schafer W, Korting HC, Hube B. 1998. Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity. Mol Microbiol 29:605-615. http://dx.doi.org/10.1046/j.1365-2958.1998.00957.x.
56. Schaller M, Bein M, Korting HC, Baur S, Hamm G, Monod M, Beinhauer S, Hube B. 2003. The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium. Infect Immun 71:3227-3234. http://dx.doi.org/10.1128/IAI.71.6.3227-3234.2003.
57. Schaller M, Korting HC, Schafer W, Baster J, Chen W, Hube B. 1999. Secreted aspartic proteinase (Sap) activity contributes to tissue damage in a model of human oral candidosis. Mol Microbiol 34:169-180. http://dx.doi.org/10.1046/j.1365-2958.1999.01590.x.
58. Meiller TF, Hube B, Schild L, Shirtliff ME, Scheper MA, Winkler R, Ton A, Jabra-Rizk MA. 2009. A novel immune evasion strategy of Candida albicans: proteolytic cleavage of a salivary antimicrobial peptide. PLoS One 4:e5039. http://dx.doi.org/10.1371/journal.pone.0005039.
59. Schild L, Heyken A, de Groot PWJ, Hiller E, Mock M, de Koster C, Horn U, Rupp S, Hube B. 2011. Proteolytic cleavage of covalently linked cell wall proteins by Candida albicans Sap9 and Sap10. Eukaryot Cell 10: 98-109. http://dx.doi.org/10.1128/EC.00210-10.
60. Staniszewska M, Bondaryk M, Siennicka K, Pilat J, Schaller M, Kurzatkowski W. 2012. Role of aspartic proteinases in Candida albicans virulence. Part I. Substrate specificity of aspartic proteinases and Candida albicans pathogenesis. Postepy Mikrobiol 51:127-135. http://www.pm.microbiology.pl/web/archiwum/vol5122012127.pdf.
61. Shoham S, Levitz SM. 2005. The immune response to fungal infections. Br J Haematol 129:569-582. http://dx.doi.org/10.1111/j.1365-2141.2005.05397.x.
62. Schaller M, Januschke E, Schackert C, Woerle B, Korting HC. 2001. Different isoformsof secreted aspartyl proteinases(Sap)areexpressedbyCandida albicans during oral and cutaneous candidosis in vivo. J Med Microbiol 50:743-747. http://jmm.sgmjournals.org/content/50/8/743.long.
63. Argimón S, Wishart JA, Leng R, Macaskill S, Mavor A, Alexandris T, Nicholls S, Knight AW, Enjalbert B, Walmsley R, Odds FC, Gow NA, Brown AJ. 2007. Developmental regulation of an adhesin gene during cellular morphogenesis in the fungal pathogen Candida albicans. Eukaryot Cell 6:682-692. http://dx.doi.org/10.1128/EC.00340-06.
64. Décanis N, Tazi N, Correia A, Vilanova M, Rouabhia M. 2011. Farnesol, a fungal quorum-sensing molecule, triggers Candida albicans morphological changes by downregulating the expression of different secreted aspartyl proteinase genes. Open Microbiol J 5:119-126. http://dx.doi.org/10.2174/1874285801105010119.
65. Zakikhany K, Naglik JR, Schmidt-Westhausen A, Holland G, Schaller M, Hube B. 2007. In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell Microbiol 9:2938-2954. http://dx.doi.org/10.1111/j.1462-5822.2007.01009.x.
66. Vandamme D, Landuyt B, Luyten W, Schoofs L. 2012. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol 280:22-35. http://dx.doi.org/10.1016/j.cellimm.2012.11.009.
67. Wong JH, Ng TB, Legowska A, Rolka K, Hui M, Cho CH. 2011. Antifungal action of human cathelicidin fragment (LL13-37) on Candida albicans. Peptides 32:1996-2002. http://dx.doi.org/10.1016/j.peptides.2011.08.018.
68. Murakami M, Lopez-Garcia B, Braff M, Dorschner RA, Gallo RL. 2004. Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 172:3070-3077. http://dx.doi.org/10.4049/jimmunol.172.5.3070.
69. Yamasaki K, Schauber J, Coda A, Lin H, Dorschner RA, Schechter NM, Bonnart C, Descargues P, Hovnanian A, Gallo RL. 2006. Kallikreinmediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 20:2068-2080. http://dx.doi.org/10.1096/fj.06-6075com.
70. Hünniger K, Lehnert T, Bieber K, Martin R, Figge MT, Kurzai O. 2014. A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood. PLoS Comput Biol 10: e1003479. http://dx.doi.org/10.1371/journal.pcbi.1003479.
71. Miramón P, Kasper L, Hube B. 2013. Thriving within the host: Candida spp. interactions with phagocytic cells. Med Microbiol Immunol 202:183-195. http://dx.doi.org/10.1007/s00430-013-0288-z.
72. Watson RW, O'Neill A, Brannigan AE, Brannigen AE, Coffey R, Marshall JC, Brady HR, Fitzpatrick JM. 1999. Regulation of Fas antibody induced neutrophil apoptosis is both caspase and mitochondrial dependent. FEBS Lett 453:67-71. http://dx.doi.org/10.1016/S0014-5793(99)00688-2.
73. Zhang Z, Cherryholmes G, Shively JE. 2008. Neutrophil secondary necrosis is induced by LL-37 derived from cathelicidin. J Leukoc Biol 84:780-788. http://dx.doi.org/10.1189/jlb.0208086.
74. De Yang Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O. 2000. LL-37, the neutrophil granule-and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069-1074. http://dx.doi.org/10.1084/jem.192.7.1069.
75. Gillum AM, Tsay EY, Kirsch DR. 1984. Isolation of the Candida albicans gene for orotidine-5'-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198:179-182. http://dx.doi.org/10.1007/BF00328721.
76. Fonzi WA, Irwin MY. 1993. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134:717-728.
77. Murad AM, Lee PR, Broadbent ID, Barelle CJ, Brown AJ. 2000. CIp10, an efficient and convenient integrating vector for Candida albicans. Yeast 16: 325-327. http://dx.doi.org/10.1002/1097-0061(20000315)16:4<325::AID-YEA538>3.0.CO;2-#.
78. Kretschmar M, Felk A, Staib P, Schaller M, Hess D, Callapina M, Morschhäuser J, Schäfer W, Korting HC, Hof H, Hube B, Nichterlein T. 2002. Individual acid aspartic proteinases (Saps) 1-6 of Candida albicans are not essential for invasion and colonization of the gastrointestinal tract in mice. Microb Pathog 32:61-70. http://dx.doi.org/10.1006/mpat.2001.0478.
79. Sanglard D, Hube B, Monod M, Odds FC, Gow NA. 1997. A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence. Infect Immun 65:3539-3546.
80. Puri S, Kumar R, Chadha S, Tati S, Conti HR, Hube B, Cullen PJ, Edgerton M. 2012. Secreted aspartic protease cleavage of Candida albicans Msb2 activates Cek1 MAPK signaling affecting biofilm formation and oropharyngeal candidiasis. PLoS One 7:e46020. http://dx.doi.org/10.1371/journal.pone.0046020.
81. Wartenberg A, Linde J, Martin R, Schreiner M, Horn F, Jacobsen ID, Jenull S, Wolf T, Kuchler K, Guthke R, Kurzai O, Forche A, d'Enfert C, Brunke S, Hube B. 2014. Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant. PLoS Genet 10:e1004824. http://dx.doi.org/10.1371/journal.pgen.1004824.