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Cited by 489Bacterial Genetics and BiotechnologyBacillus and Francisella bacterial researchBacterial biofilms and quorum sensing

A Eukaryotic-like Ser/Thr Kinase Signals Bacteria to Exit Dormancy in Response to Peptidoglycan Fragments

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Shah, Ishita M., Laaberki, Maria-Halima, Popham, David L., Dworkin, Jonathan·2008·Cell
DOI 10.1016/j.cell.2008.08.039PMC PMC2892110
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Abstract

Bacteria can respond to adverse environmental conditions by drastically reducing or even ceasing metabolic activity. They must then determine that conditions have improved before exiting dormancy, and one indication of such a change is the growth of other bacteria in the local environment. Growing bacteria release muropeptide fragments of the cell wall into the extracellular milieu, and we report here that these muropeptides are potent germinants of dormant Bacillus subtilis spores. The ability of a muropeptide to act as a germinant is determined by the identity of a single amino acid. A well-conserved, eukaryotic-like Ser/Thr membrane kinase containing an extracellular domain capable of binding peptidoglycan is necessary for this response, and a small molecule that stimulates related eukaryotic kinases is sufficient to induce germination. Another small molecule, staurosporine, that inhibits related eukaryotic kinases blocks muropeptide-dependent germination. Thus, in contrast to traditional antimicrobials that inhibit metabolically active cells, staurosporine acts by blocking germination of dormant spores.

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  • Peptidoglycan fragments may play roles in more mature biofilms as environmental cues, since they regulate processes such as germination of spores in Bacillus, production of antimicrobial compounds by P. aeruginosa, and yeast-hyphal transition in C. albicans.

    “peptidoglycan fragments may play roles in more mature biofilms as environmental cues, since it has been demonstrated that they regulate processes such as the germination of spores in Bacillus, the production of antimicrobial compounds by P. aeruginosa, and the yeast-hyphal transition in C. albicans.173–175”

    From The dental plaque biofilm matrix (2021) · cites this paper as [173]

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Research works printed but not linked: 48

  1. Atrih A Bacher G Allmaier G Williamson MP Foster SJ 1999 Analysis of peptidoglycan structure from vegetative cells of Bacillus subtilis 168 and role of PBP 5 in peptidoglycan maturation J Bacteriol 181 3956 3966 10383963 PMC93885
  2. Bassler BL Losick R 2006 Bacterially speaking Cell 125 237 246 16630813
  3. Bettegowda C Huang X Lin J Cheong I Kohli M Szabo SA Zhang X Diaz LA Jr Velculescu VE Parmigiani G 2006 The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT Nat Biotechnol 24 1573 1580 17115055 PMC9338427
  4. Beveridge TJ 1999 Structures of gram-negative cell walls and their derived membrane vesicles J Bacteriol 181 4725 4733 10438737 PMC93954
  5. Chambon P Deutscher MP Kornberg A 1968 Biochemical studies of bacterial sporulation and germination. X. Ribosomes and nucleic acids of vegetative cells and spores of Bacillus megaterium J Biol Chem 243 5110 5116 4971348
  6. Chang CI Chelliah Y Borek D Mengin-Lecreulx D Deisenhofer J 2006 Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor Science 311 1761 1764 16556841
  7. Cloud-Hansen KA Peterson SB Stabb EV Goldman WE McFaa-Ngai MJ Handelsman J 2006 Breaching the great wall: peptidoglycan and microbial interactions Nat Rev Microbiol 4 710 716 16894338
  8. D’Elia MA Millar KE Beveridge TJ Brown ED 2006 Wall teichoic acid polymers are dispensable for cell viability in Bacillus subtilis J Bacteriol 188 8313 8316 17012386 PMC1698200
  9. Dasgupta A Datta P Kundu M Basu J 2006 The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division Microbiology 152 493 504 16436437
  10. Doyle RJ Chaloupka J Vinter V 1988 Turnover of cell walls in microorganisms Microbiol Rev 52 554 567 3070324 PMC373163
  11. Driks A 1999 Bacillus subtilis spore coat Microbiol Mol Biol Rev 63 1 20 10066829 PMC98955
  12. Eckert C Lecerf M Dubost L Arthur M Mesnage S 2006 Functional analysis of AtlA, the major N-acetylglucosaminidase of Enterococcus faecalis J Bacteriol 188 8513 8519 17041059 PMC1698247
  13. Gaidenko TA Kim TJ Price CW 2002 The PrpC serine-threonine phosphatase and PrkC kinase have opposing physiological roles in stationary-phase Bacillus subtilis cells J Bacteriol 184 6109 6114 12399479 PMC151969
  14. Gilmore ME Bandyopadhyay D Dean AM Linnstaedt SD Popham DL 2004 Production of muramic delta-lactam in Bacillus subtilis spore peptidoglycan J Bacteriol 186 80 89 14679227 PMC303458
  15. Girardin SE Travassos LH Herve M Blanot D Boneca IG Philpott DJ Sansonetti PJ Mengin-Lecreulx D 2003 Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2 J Biol Chem 278 41702 41708 12871942
  16. Goodell EW Schwarz U 1985 Release of cell wall peptides into culture medium by exponentially growing Escherichia coli J Bacteriol 162 391 397 2858468 PMC219001
  17. Hale KJ Hummersone MG Manaviazar S Frigerio M 2002 The chemistry and biology of the bryostatin antitumour macrolides Nat Prod Rep 19 413 453 12195811
  18. Hasegawa M Yang K Hashimoto M Park JH Kim YG Fujimoto Y Nunez G Fukase K Inohara N 2006 Differential release and distribution of Nod1 and Nod2 immunostimulatory molecules among bacterial species and environments J Biol Chem 281 29054 29063 16870615
  19. Hecht DW Galang MA Sambol SP Osmolski JR Johnson S Gerding DN 2007 In vitro activities of 15 antimicrobial agents against 110 toxigenic clostridium difficile clinical isolates collected from 1983 to 2004 Antimicrob Agents Chemother 51 2716 2719 17517836 PMC1932509
  20. Hudson KD Corfe BM Kemp EH Feavers IM Coote PJ Moir A 2001 Localization of GerAA and GerAC proteins in the Bacillus subtilis spore J Bacteriol 183 4317 4322 11418573 PMC95322
  21. Hungerer KD Tipper DJ 1969 Cell wall polymers of Bacillus sphaericus 9602. I. Structure of the vegetative cell wall peptidoglycan Biochemistry 8 3577 3587 5387524
  22. Jones G Dyson P 2006 Evolution of transmembrane protein kinases implicated in coordinating remodeling of gram-positive peptidoglycan: inside versus outside J Bacteriol 188 7470 7476 16936012 PMC1636289
  23. Kaeberlein T Lewis K Epstein SS 2002 Isolating “uncultivable” microorganisms in pure culture in a simulated natural environment Science 296 1127 1129 12004133
  24. Kaparakis M Philpott DJ Ferrero RL 2007 Mammalian NLR proteins; discriminating foe from friend Immunol Cell Biol 85 495 502 17680011
  25. Keep NH Ward JM Cohen-Gonsaud M Henderson B 2006 Wake up! Peptidoglycan lysis and bacterial non-growth states Trends Microbiol 14 271 276 16675219
  26. Lim JH Kim MS Kim HE Yano T Oshima Y Aggarwal K Goldman WE Silverman N Kurata S Oh BH 2006 Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins J Biol Chem 281 8286 8295 16428381
  27. Madec E Laszkiewicz A Iwanicki A Obuchowski M Seror S 2002 Characterization of a membrane-linked Ser/Thr protein kinase in Bacillus subtilis, implicated in developmental processes Mol Microbiol 46 571 586 12406230
  28. Mauck J Chan L Glaser L 1971 Turnover of the cell wall of Gram-positive bacteria J Biol Chem 246 1820 1827 4993960
  29. McPherson DC Popham DL 2003 Peptidoglycan synthesis in the absence of class A penicillin-binding proteins in Bacillus subtilis J Bacteriol 185 1423 1431 12562814 PMC142859
  30. Mukamolova GV Murzin AG Salina EG Demina GR Kell DB Kaprelyants AS Young M 2006 Muralytic activity of Micrococcus luteus Rpf and its relationship to physiological activity in promoting bacterial growth and resuscitation Mol Microbiol 59 84 98 16359320
  31. Nicholson WL Munakata N Horneck G Melosh HJ Setlow P 2000 Resistance of Bacillus endospores to extreme terrestrial and extraterrestrial environments Microbiol Mol Biol Rev 64 548 572 10974126 PMC99004
  32. Onaka H Taniguchi S Igarashi Y Furumai T 2002 Cloning of the staurosporine biosynthetic gene cluster from Streptomyces sp. TP-A0274 and its heterologous expression in Streptomyces lividans J Antibiot (Tokyo) 55 1063 1071 12617516
  33. Paidhungat M Setlow P 2000 Role of ger proteins in nutrient and nonnutrient triggering of spore germination in Bacillus subtilis J Bacteriol 182 2513 2519 10762253 PMC111315
  34. Paidhungat M Setlow P 2001 Localization of a germinant receptor protein (GerBA) to the inner membrane of Bacillus subtilis spores J Bacteriol 183 3982 3990 11395462 PMC95281
  35. Ruegg UT Burgess GM 1989 Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases Trends Pharmacol Sci 10 218 220 2672462
  36. Ryazanov AG Shestakova EA Natapov PG 1988 Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation Nature 334 170 173 3386756
  37. Santelli E Liddington RC Mohan MA Hoch JA Szurmant H 2007 The crystal structure of Bacillus subtilis YycI reveals a common fold for two members of an unusual class of sensor histidine kinase regulatory proteins J Bacteriol 189 3290 3295 17307848 PMC1855859
  38. Savelsbergh A Katunin VI Mohr D Peske F Rodnina MV Wintermeyer W 2003 An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation Mol Cell 11 1517 1523 12820965
  39. Schleifer KH Kandler O 1972 Peptidoglycan types of bacterial cell walls and their taxonomic implications Bacteriol Rev 36 407 477 4568761 PMC408328
  40. Sebaihia M Wren BW Mullany P Fairweather NF Minton N Stabler R Thomson NR Roberts AP Cerdeno-Tarraga AM Wang H 2006 The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome Nat Genet 38 779 786 16804543
  41. Setlow P 2003 Spore germination Curr Opin Microbiol 6 550 556 14662349
  42. Setlow P Kornberg A 1970 Biochemical studies of bacterial sporulation and germination. 23. Nucleotide metabolism during spore germination J Biol Chem 245 3645 3652 4990475
  43. Sharma K Gupta M Krupa A Srinivasan N Singh Y 2006 EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium tuberculosis FEBS J 273 2711 2721 16817899
  44. Steen A Buist G Leenhouts KJ El Khattabi M Grijpstra F Zomer AL Venema G Kuipers OP Kok J 2003 Cell wall attachment of a widely distributed peptidoglycan binding domain is hindered by cell wall constituents J Biol Chem 278 23874 23881 12684515
  45. Swaminathan CP Brown PH Roychowdhury A Wang Q Guan R Silverman N Goldman WE Boons GJ Mariuzza RA 2006 Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs) Proc Natl Acad Sci USA 103 684 689 16407132 PMC1334652
  46. Tufariello JM Mi K Xu J Manabe YC Kesavan AK Drumm J Tanaka K Jacobs WR Jr Chan J 2006 Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis Infect Immun 74 2985 2995 16622237 PMC1459759
  47. Yeats C Finn RD Bateman A 2002 The PASTA domain: a betalactam-binding domain Trends Biochem Sci 27 438 12217513
  48. Young TA Delagoutte B Endrizzi JA Falick AM Alber T 2003 Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases Nat Struct Biol 10 168 174 12548283

Cited by

Sorted by citations

Authors
Shah, I. M., Laaberki, M.-H., Popham, D. L., & Dworkin, J.
Affiliations
  • Columbia University (US)
  • Virginia Tech (US)
Corresponding author
Dworkin, Jonathan
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2008-10
Volume
135
Issue
3
Pages
486-496
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2008.08.039
PMC
PMC2892110
OpenAlex
W1966023562
Cited by
489
References
1
Citations by year
2026: 9 · 2025: 19 · 2024: 6 · 2023: 19 · 2022: 21 · 2021: 21 · 2020: 28 · 2019: 32 · 2018: 26 · 2017: 28 · 2016: 29 · 2015: 33 · 2014: 32 · 2013: 37 · 2012: 42
FWCI
18.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Irma T. Hirschl Trust
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM56695, R01GM081368, R01GM056695)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacillus and Francisella bacterial research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords
Bacillus subtilis, spore germination, dormancy, muropeptides, peptidoglycan fragments, Ser/Thr kinase, extracellular signaling, staurosporine, germinants, bacterial quorum sensing, cell wall
MeSH terms
Acetylmuramyl-Alanyl-Isoglutamine, Bacillus subtilis, Bacterial Proteins, Cell Membrane, Oligopeptides, Peptidoglycan, Phosphorylation, Spores, Bacterial, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Staurosporine

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