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
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Raději si zajděte na oční! Jak souvisí citlivost zraku s rozvojem demence?
- Co způsobuje pooperační infekce? Na vině může být i naše vlastní mikrobiota
- Čeká nás průlom v diagnostice karcinomu pankreatu?
- Polibek, který mi „vzal nohy“ aneb vzácný výskyt EBV u 70leté ženy – kazuistika
Nejčtenější v tomto čísle
- AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization
- Osteocalcin promotes bone mineralization but is not a hormone
- Super-resolution imaging of RAD51 and DMC1 in DNA repair foci reveals dynamic distribution patterns in meiotic prophase
- Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis