#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae


Autoři: Avatar Joshi aff001;  Samar A. Mahmoud aff002;  Soo-Kyoung Kim aff003;  Justyne L. Ogdahl aff002;  Vincent T. Lee aff003;  Peter Chien aff002;  Fitnat H. Yildiz aff001
Působiště autorů: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America aff001;  Department of Biochemistry and Molecular Biology, Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts, United States of America aff002;  Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America aff003
Vyšlo v časopise: c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008897
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008897

Souhrn

The LonA (or Lon) protease is a central post-translational regulator in diverse bacterial species. In Vibrio cholerae, LonA regulates a broad range of behaviors including cell division, biofilm formation, flagellar motility, c-di-GMP levels, the type VI secretion system (T6SS), virulence gene expression, and host colonization. Despite LonA’s role in cellular processes critical for V. cholerae’s aquatic and infectious life cycles, relatively few LonA substrates have been identified. LonA protease substrates were therefore identified through comparison of the proteomes of wild-type and ΔlonA strains following translational inhibition. The most significantly enriched LonA-dependent protein was TfoY, a known regulator of motility and the T6SS in V. cholerae. Experiments showed that TfoY was required for LonA-mediated repression of motility and T6SS-dependent killing. In addition, TfoY was stabilized under high c-di-GMP conditions and biochemical analysis determined direct binding of c-di-GMP to LonA results in inhibition of its protease activity. The work presented here adds to the list of LonA substrates, identifies LonA as a c-di-GMP receptor, demonstrates that c-di-GMP regulates LonA activity and TfoY protein stability, and helps elucidate the mechanisms by which LonA controls important V. cholerae behaviors.

Klíčová slova:

Biofilms – Gene expression – Cholera – Pathogen motility – Proteases – Proteolysis – Regulator genes – Secretion systems


Zdroje

1. Mahmoud SA, Chien P. Regulated Proteolysis in Bacteria. Annu Rev Biochem. 2018;87: 677–696. doi: 10.1146/annurev-biochem-062917-012848 29648875

2. Olivares AO, Baker TA, Sauer RT. Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines. Nat Rev Microbiol. 2016;14: 33–44. doi: 10.1038/nrmicro.2015.4 26639779

3. Gur E, Biran D, Ron EZ. Regulated proteolysis in Gram-negative bacteria—how and when? Nat Rev Microbiol. 2011;9: 839–848. doi: 10.1038/nrmicro2669 22020261

4. Rogers A, Townsley L, Gallego-Hernandez AL, Beyhan S, Kwuan L, Yildiz FH. The LonA Protease Regulates Biofilm Formation, Motility, Virulence, and the Type VI Secretion System in Vibrio cholerae. J Bacteriol. 2016;198: 973–85. doi: 10.1128/JB.00741-15 26755629

5. Xie F, Li G, Zhang Y, Zhou L, Liu S, Liu S, et al. The Lon protease homologue LonA, not LonC, contributes to the stress tolerance and biofilm formation of Actinobacillus pleuropneumoniae. Microb Pathog. 2016;93: 38–43. doi: 10.1016/j.micpath.2016.01.009 26796296

6. He L, Nair MKM, Chen Y, Liu X, Zhang M, Hazlett KRO, et al. The protease locus of Francisella tularensis LVS is required for stress tolerance and infection in the mammalian host. Infect Immun. 2016;84: 1387–1402. doi: 10.1128/IAI.00076-16 26902724

7. Breidenstein EBM, Janot L, Strehmel J, Fernandez L, Taylor PK, Kukavica-Ibrulj I, et al. The Lon Protease Is Essential for Full Virulence in Pseudomonas aeruginosa. PLoS ONE. 2012;7. doi: 10.1371/journal.pone.0049123 23145092

8. Pressler K, Vorkapic D, Lichtenegger S, Malli G, Barilich BP, Cakar F, et al. AAA+ proteases and their role in distinct stages along the Vibrio cholerae lifecycle. Int J Med Microbiol IJMM. 2016;306: 452–62. doi: 10.1016/j.ijmm.2016.05.013 27345492

9. Takaya A, Tomoyasu T, Tokumitsu A, Morioka M, Yamamoto T. The ATP-Dependent Lon Protease of Salmonella enterica Serovar Typhimurium Regulates Invasion and Expression of Genes Carried on Salmonella Pathogenicity Island 1. Society. 2002;184: 224–232. doi: 10.1128/JB.184.1.224

10. Lan L, Deng X, Xiao Y, Zhou J-M, Tang X. Mutation of Lon protease differentially affects the expression of Pseudomonas syringae type III secretion system genes in rich and minimal media and reduces pathogenicity. Mol Plant-Microbe Interact MPMI. 2007;20: 682–96. doi: 10.1094/MPMI-20-6-0682 17555276

11. Ching C, Yang B, Onwubueke C, Lazinski D, Camilli A, Godoy VG. Lon Protease Has Multifaceted Biological Functions in Acinetobacter baumannii. J Bacteriol. 2019;201. doi: 10.1128/JB.00536-18 30348832

12. Su S, Stephens BB, Alexandre G, Farrand SK. Lon protease of the α-proteobacterium Agrobacterium tumefaciens is required for normal growth, cellular morphology and full virulence. Microbiology. 2006;152: 1197–1207. doi: 10.1099/mic.0.28657-0 16549682

13. Sauer RT, Baker TA. AAA+ Proteases: ATP-Fueled Machines of Protein Destruction. Annu Rev Biochem. 2011;80: 587–612. doi: 10.1146/annurev-biochem-060408-172623 21469952

14. Baker TA, Sauer RT. ATP-dependent proteases of bacteria: recognition logic and operating principles. Trends Biochem Sci. 2006;31: 647–653. doi: 10.1016/j.tibs.2006.10.006 17074491

15. Proteases Gottesman S. and Their Targets in Escherichia Coli. Annu Rev Genet. 1996;30: 465–506. doi: 10.1146/annurev.genet.30.1.465 8982462

16. Mukherjee S, Bree AC, Liu J, Patrick JE, Chien P, Kearns DB. Adaptor-mediated Lon proteolysis restricts Bacillus subtilis hyperflagellation. Proc Natl Acad Sci. 2015;112: 250–255. doi: 10.1073/pnas.1417419112 25538299

17. Puri N, Karzai AW. HspQ Functions as a Unique Specificity-Enhancing Factor for the AAA+ Lon Protease. Mol Cell. 2017;66: 672–683.e4. doi: 10.1016/j.molcel.2017.05.016 28575662

18. Kuroda A, Nomura K, Ohtomo R, Kato J, Ikeda T, Takiguchi N, et al. Role of Inorganic Polyphosphate in Promoting Ribosomal Protein Degradation by the Lon Protease in E. coli. Science. 2001;293: 705–708. doi: 10.1126/science.1061315 11474114

19. Osbourne DO, Soo VW, Konieczny I, Wood TK. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity. Bioengineered. 2014;5: 264–268. doi: 10.4161/bioe.29261 24874800

20. Chung CH, Goldberg AL. DNA stimulates ATP-dependent proteolysis and protein-dependent ATPase activity of protease La from Escherichia coli. Proc Natl Acad Sci. 1982;79: 795–799. doi: 10.1073/pnas.79.3.795 6461007

21. Ali M, Nelson AR, Lopez AL, Sack DA. Updated Global Burden of Cholera in Endemic Countries. PLoS Negl Trop Dis. 2015;9. doi: 10.1371/journal.pntd.0003832 26043000

22. Joshi A, Kostiuk B, Rogers A, Teschler J, Pukatzki S, Yildiz FH. Rules of Engagement: The Type VI Secretion System in Vibrio cholerae. Trends Microbiol. 2017;25: 267–279. doi: 10.1016/j.tim.2016.12.003 28027803

23. Lee K-J, Jung Y-C, Park S-J, Lee K-H. Role of Heat Shock Proteases in Quorum-Sensing-Mediated Regulation of Biofilm Formation by Vibrio Species. mBio. 2018;9: e02086–17. doi: 10.1128/mBio.02086-17 29295912

24. Metzger LC, Stutzmann S, Scrignari T, Van der Henst C, Matthey N, Blokesch M. Independent Regulation of Type VI Secretion in Vibrio cholerae by TfoX and TfoY. Cell Rep. 2016;15: 951–8. doi: 10.1016/j.celrep.2016.03.092 27117415

25. Bao Y, Lies DP, Fu H, Roberts GP. An improved Tn7-based system for the single-copy insertion of cloned genes into chromosomes of gram-negative bacteria. Gene. 1991;109: 167–168. doi: 10.1016/0378-1119(91)90604-a 1661697

26. Pursley Ben; Maiden Michael; Waters C. Cyclic di-GMP regulates TfoY in Vibrio cholerae to control motility by both transcriptional and posttranscriptional mechanisms. Mol Microbiol. 2017.

27. Inuzuka S, Nishimura K-I, Kakizawa H, Fujita Y, Furuta H, Matsumura S, et al. Mutational analysis of structural elements in a class-I cyclic di-GMP riboswitch to elucidate its regulatory mechanism. J Biochem (Tokyo). 2016;160: 153–162. doi: 10.1093/jb/mvw026 27033943

28. Inuzuka S, Kakizawa H, Nishimura K, Naito T, Miyazaki K, Furuta H, et al. Recognition of cyclic-di-GMP by a riboswitch conducts translational repression through masking the ribosome-binding site distant from the aptamer domain. Genes Cells. 2018;23: 435–447. doi: 10.1111/gtc.12586 29693296

29. Roelofs KG, Wang J, Sintim HO, Lee VT. Differential radial capillary action of ligand assay for high-throughput detection of protein-metabolite interactions. Proc Natl Acad Sci U S A. 2011;108: 15528–15533. doi: 10.1073/pnas.1018949108 21876132

30. Sharma IM, Dhanaraman T, Mathew R, Chatterji D. Synthesis and Characterization of a Fluorescent Analogue of Cyclic di-GMP. Biochemistry. 2012;51: 5443–5453. doi: 10.1021/bi3003617 22715917

31. Liu Z, Miyashiro T, Tsou A, Hsiao A, Goulian M, Zhu J. Mucosal penetration primes Vibrio cholerae for host colonization by repressing quorum sensing. Proc Natl Acad Sci. 2008;105: 9769–9774. doi: 10.1073/pnas.0802241105 18606988

32. Correa NE, Barker JR, Klose KE. The Vibrio cholerae FlgM Homologue Is an Anti-σ28 Factor That Is Secreted through the Sheathed Polar Flagellum. J Bacteriol. 2004;186: 4613–4619. doi: 10.1128/JB.186.14.4613-4619.2004 15231794

33. Jaskólska M, Gerdes K. CRP-dependent Positive Autoregulation and Proteolytic Degradation Regulate Competence Activator Sxy of Escherichia coli. Mol Microbiol. 2015;95: 833–845. doi: 10.1111/mmi.12901 25491382

34. Meibom KL. Chitin Induces Natural Competence in Vibrio cholerae. Science. 2005;310: 1824–1827. doi: 10.1126/science.1120096 16357262

35. Redfield RJ. sxy-1, a Haemophilus influenzae mutation causing greatly enhanced spontaneous competence. J Bacteriol. 1991;173: 5612–5618. doi: 10.1128/jb.173.18.5612-5618.1991 1653215

36. Sinha S, Redfield RJ. Natural DNA Uptake by Escherichia coli. PLOS ONE. 2012;7: e35620. doi: 10.1371/journal.pone.0035620 22532864

37. Metzger LC, Matthey N, Stoudmann C, Collas EJ, Blokesch M. Ecological implications of gene regulation by TfoX and TfoY among diverse Vibrio species. Environ Microbiol. 2019. doi: 10.1111/1462-2920.14562 30761714

38. Zamorano-Sánchez D, Xian W, Lee CK, Salinas M, Thongsomboon W, Cegelski L, et al. Functional Specialization in Vibrio cholerae Diguanylate Cyclases: Distinct Modes of Motility Suppression and c-di-GMP Production. mBio. 2019;10: e00670–19. doi: 10.1128/mBio.00670-19 31015332

39. Liu X, Beyhan S, Lim B, Linington RG, Yildiz FH. Identification and Characterization of a Phosphodiesterase That Inversely Regulates Motility and Biofilm Formation in Vibrio cholerae. J Bacteriol. 2010;192: 4541–4552. doi: 10.1128/JB.00209-10 20622061

40. Lim B, Beyhan S, Meir J, Yildiz FH. Cyclic-diGMP signal transduction systems in Vibrio cholerae: modulation of rugosity and biofilm formation. Mol Microbiol. 2006;60: 331–348. doi: 10.1111/j.1365-2958.2006.05106.x 16573684

41. Sudarsan N, Lee ER, Weinberg Z, Moy RH, Kim JN, Link KH, et al. Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP. Science. 2008;321: 411–413. doi: 10.1126/science.1159519 18635805

42. Pursley BR, Fernandez NL, Severin GB, Waters CM. The Vc2 Cyclic di-GMP-Dependent Riboswitch of Vibrio cholerae Regulates Expression of an Upstream Putative Small RNA by Controlling RNA Stability. J Bacteriol. 2019;201. doi: 10.1128/JB.00293-19 31405916

43. Orr MW, Galperin MY, Lee VT. Sustained sensing as an emerging principle in second messenger signaling systems. Curr Opin Microbiol. 2016;34: 119–126. doi: 10.1016/j.mib.2016.08.010 27700990

44. Wohlever ML, Nager AR, Baker TA, Sauer RT. Engineering fluorescent protein substrates for the AAA+ Lon protease. Protein Eng Des Sel PEDS. 2013;26: 299–305. doi: 10.1093/protein/gzs105 23359718

45. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US); 2011. Available: http://www.ncbi.nlm.nih.gov/books/NBK54050/ doi: 10.1258/la.2010.010031 21123303

46. Fong JCN, Karplus K, Schoolnik GK, Yildiz FH. Identification and Characterization of RbmA, a Novel Protein Required for the Development of Rugose Colony Morphology and Biofilm Structure in Vibrio cholerae. J Bacteriol. 2006;188: 1049–1059. doi: 10.1128/JB.188.3.1049-1059.2006 16428409

47. Zamorano-Sánchez D, Fong JCN, Kilic S, Erill I, Yildiz FH. Identification and Characterization of VpsR and VpsT Binding Sites in Vibrio cholerae. J Bacteriol. 2015;197: 1221–1235. doi: 10.1128/JB.02439-14 25622616

48. Chapman JR, Katsara O, Ruoff R, Morgenstern D, Nayak S, Basilico C, et al. Phosphoproteomics of FGF1 signaling in chondrocytes: Identifying the signature of inhibitory response. Mol Cell Proteomics MCP. 2017. doi: 10.1074/mcp.M116.064980 28298517

49. Bhardwaj A, Yang Y, Ueberheide B, Smith S. Whole proteome analysis of human tankyrase knockout cells reveals targets of tankyrase-mediated degradation. Nat Commun. 2017;8: 2214. doi: 10.1038/s41467-017-02363-w 29263426

50. Jonas K, Liu J, Chien P, Laub MT. Proteotoxic Stress Induces a Cell-Cycle Arrest by Stimulating Lon to Degrade the Replication Initiator DnaA. Cell. 2013;154: 623–636. doi: 10.1016/j.cell.2013.06.034 23911325

51. Teschler JK, Cheng AT, Yildiz FH. The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation. J Bacteriol. 2017;199: e00139–17. doi: 10.1128/JB.00139-17 28607158


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 6
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Hypertenze a hypercholesterolémie – synergický efekt léčby
nový kurz
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Úloha kombinovaných preparátů v léčbě arteriální hypertenze
Autoři: prof. MUDr. Martin Haluzík, DrSc.

Halitóza
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Terapie roztroušené sklerózy v kostce
Autoři: MUDr. Dominika Šťastná, Ph.D.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#