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1 2014 Quorum Sensing Jo, Sung Jun

2 Angler fish( 심해아귀 ) In the deep ocean where light is scarce, the angler fish makes clever use of bacteria's ability to shine through quorum-sensing.

3 How bacteria "talk" - Bonnie Bassler

4 Quorum sensing Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density.

5 Quorum sensing Pheromones = signal molecules, pathogen factors = group behavior Ref.

6 Quorum sensing High cell density Group behavior regulation * Luminescence * Biofilm formation * Virulence, Symbiosis, Sporulation, etc. : Bacteria : Signal molecules (autoinducer)

7 Examples of group behavior by QS 1) Luminescence 2) Biofilm formation 3) Virulence

8 1) Luminescence Bobtail squid & Vibrio fischeri * Vibrio fischeri: 쿼럼센싱이최초로발견된박테리아

9 1) Luminescence- Hawaiian bobtail squid (A) 어린 bobtail squid, e, 눈 ; lo, 발광기관. (B) 발광기관의단면도 b, in the crypt lumen, the ink sac (is) and reflector (r); hg, hindgut. (C) Light cycles experienced by E. scolopes Elizabeth A. C. et al., Mbio., 2014

10 1) Luminescence - Hawaiian bobtail squid 낮에는해저속모래또는바닥과같은색의보호색을띔 밤에는이동중달빛으로인한그림자를없애기위해서발광기관의밝기를조절하며이동

11 2) Biofilm formation

12 2) Biofilm formation Staphylococcus aureus biofilm Biofilm in Yellowstone National Park Biofilm on membrane for wastewater treatment

13 3) Virulence 세균자신이숙주의방어체계를피하면서효과적으로숙주를공격하여감염 에성공하기위한전략 ( 에너지낭비와면역기작유발을피함 ) 일정농도의개체수에도달해서병원성을나타내기에충분한세균밀도가되 었을경우에만감염에필요한다양한발병력요소유전자의발현을촉진하여 모든세포가일시에숙주를공격하도록유도 13

Serratia liquefacience * 어병균 Aeromonas hydrophila, Vibrio

14 3) Virulence * 섬유성낭포증 (cystic fibrosis) 환자의호흡기감염 Pseudomonas aeruginosa, Burkholderia cepacia * 포유류에대한병원균 Serratia liquefacience * 어병균 Aeromonas hydrophila, Vibrio anguillarum * 식물병원균 Erwinia carotovora, Agrobacterium tumefaciens

15 Structure of autoinducers (signal molecule)

16 Autoinducer (signaling molecule) N-acyl homoserine lactone (AHL) for gram-negative bacteria N H Pseudomonas aeruginosa N H ligopeptide for gram-positive bacteria Tyr Ser Cys Thr Asp Met Staphylococcus aureus S Phe Ile Autoinducer-2 (AI-2) for interspecies communication H H H B H Vibrio harveyi CH 3 H H H CH 3 H Salmonella enterica serovar Typhimurium thers - Autoinducer-3 (AI-3) Enterohaemorrhagic E. coli (EHEC) 157:H3 - Pseudomonas quinoline signal (PQS) H N H Pseudomonas aeruginosa

17 N-acyl-homoserine lactone Full name N-butyryl-homoserine lactone Synonym 4 3 (C4-HSL, BHL) N-hexanoyl-homoserine lactone (C6-HSL, HHL) 2 1 N H N H N H N-3-oxopentanoyl-homoserine lactone (3-oxo-C5-HSL, PHL) 3 N-3-oxooctanoyl-homoserine lactone (3-oxo-C8-HSL, HL) N H N-decanoyl-homoserine lactone (C10-HSL, DHL) N H H N H N-3-hydroxydecanoyl-homoserine lactone (3-H-C10-HSL, HDHL)

18 Autoinduction mechanism 1) Peptide mediated quorum sensing 2) LuxI/LuxR type (AHL) 3) AI-2 quorum sensing

19 Peptide mediated quorum sensing -. Peptide mediated quorum sensing 이가장많이연구된주요미생물 Gram-positive bacteria image Bacillus subtilis ( 고초균 ) Streptococcus pneumoniae ( 연쇄상구균 ) Staphylococci ( 포도상구균 )

20 Peptide mediated quorum sensing ligopeptide signaling molecule for grampositive bacteria Asp Phe Ile An oligopeptide (oligo-, "few") consists of between 2 and 20 amino acids. Tyr Ser Cys Thr S Met

21 Peptide mediated quorum sensing Wai-Leung Ng & Bonnie L. Bassler et al. Annu. Rev. Genet., 2009, 43,

22 Peptide quorum sensing in Staphylococci Richard P. Novick & Edward Geisinger et al. Annu. Rev. Genet., 2008, 42,

23 Autoinduction mechanism (LuxI/LuxR type) Vibrio fischeri bioluminescence system

24 Autoinduction mechanism (LuxI/LuxR type) LuxI: produces a continuous low level of freely diffusible HHL LuxR: cytoplasmic receptor, transcriptional regulator.

25 Autoinduction mechanism (LuxI/LuxR type) A. tumefaciens: a plant pathogen TraI: LuxI homologue TraR: LuxR homologue

26 How can signal molecules pass through the cell membrane? Two-component regulatory system (2 성분조절체계 ) Cytoplasmic receptor(ai-1) -. 2 성분조절체계는 Prokaryotes 에서보편적인정보전달체계임 Wikipedia 2013 년 7 월검색,

27 Quorum sensing signal molecule Intra-species cell to cell communication Inter-species cell to cell communication : Bacteria speices : Signal molecules 3

28 Intra-species quorum sensing : Bacteria speices Gram (-) bacteria N-acyl homoserine lactone (AHL) Gram (+) bacteria ligopeptide Intra-species cell to cell communication Waters and Bassler, Annu. Rev. Cell Dev. Biol

29 Inter-species quorum sensing: AI-2 Inter-speices cell to cell communication (Autoinducer-2, AI-2) Homologue of luxs (DPD) in well over 80 species AI-2 signal molecule : Bacteria species Waters and Bassler, Annu. Rev. Cell Dev. Biol

30 AI-2 Quorum sensing - AI-2 production has been observed in many species using the V. harveyi BB170 reporter strain, The Type of Bacteria Containing LuxS Melissa B. Miller et al., Annu. Rev. Microbiol., 2001 Peng Zhu et al., Current Medicinal Chemistry, 2012

AI-2 Quorum sensing in Vibrio harveyi At Low cell density 1 2 3 Not been determined 3-H-C4-homoserine lactone Furanosyl borate diester CqsA: Cholerae quorum-sensing autoinducer CqsS: Cholerae

31 AI-2 Quorum sensing in Vibrio harveyi At Low cell density Not been determined 3-H-C4-homoserine lactone Furanosyl borate diester CqsA: Cholerae quorum-sensing autoinducer CqsS: Cholerae quorum-sensing sensor LuxU P cqss, LuxN & LuxQ 가 kinase 로반응 P Lux σ 54 (transcription factor) Biofilm Virulence ther gene 5 Qrr srnas luxr(mrna) LuxR Hfq (chaperone) mrna splicing 에관여 luxcdabe Waters and Bassler, Annu. Rev. Cell Dev. Biol., 2005

32 At Low cell density 1) Signal molecule sensor 인 cqss, LuxN & LuxQ 가 kinase 로반응 2) Phosphate 가 LuxU 에서 Lux 와결합 3) Phospho Lux 가 σ 54 (transcription factor) 와같이 5 가지 Qrr srnas 를활성화 4) 5 가지 Qrr srnas 가 mrna splicing 에관여하는것으로알려진 Hfq (chaperone) 와상호작용 5) luxr(mrna) 를불안정하게하여 Luminescence 관련유전자의전사를 inhibition

AI-2 Quorum sensing in Vibrio harveyi At high cell density 1 2 3 Not been determined 3-H-C4-homoserine lactone Furanosyl borate diester CqsA: Cholerae quorum-sensing autoinducer CqsS: Cholerae

33 AI-2 Quorum sensing in Vibrio harveyi At high cell density Not been determined 3-H-C4-homoserine lactone Furanosyl borate diester CqsA: Cholerae quorum-sensing autoinducer CqsS: Cholerae quorum-sensing sensor LuxU Lux P σ 54 (transcription factor) kinase cqss, LuxN & LuxQ 가 phosphatase 로반응 Biofilm Virulence ther gene 5 Qrr srnas luxr(mrna) LuxR Hfq (chaperone) luxcdabe Waters and Bassler, Annu. Rev. Cell Dev. Biol., 2005

34 At high cell density 1) Signal molecule sensor 인 cqss, LuxN & LuxQ 가 phosphatase 로반응 2) Phosphate 가 LuxU 와결합 3) Phospho LuxU 가 luxr(mrna) 전사 4) Luminescence 관련유전자활성화

35 The biosynthetic pathway of AI-2 in vivo Peng Zhu et al., Current Medicinal Chemistry, 2012 MTAN: SAH/5 -methylthioadenosine nucleosidase LuxS 는 AI-2 물질의전구체인 DPD 생산에가장중요한 enzyme 이다. S-adenosyl-methionine S-ribosyl -L-homocysteine Route 1 H 2-2H 2 +B(H) 4 LuxP Quorum Sensing Hydration of DPD Route 2 Boric acid 와반응 V. harveyi H 2 LsrB Quorum Sensing S. typhimurium

36 1) S-adenosyl-methionine(SAM) 이 methyltransferase 에의해서 S-adenosyl-L-homosysteine(SAH) 으로변화 2) S-adenosyl-L-homosysteine(SAH) 가 SAH/5 -methylthioadenosine nucleosidase 에의해서 adenine 이분리되고 S-ribosyl-L-homocysteine(SRH) 로변화 3) SRH 가 LuxS 단백질에의해서 homosysteine 이분리되고 DPD (4,5-dihydroxy-2,3-pentanedione) 가합성 Route1: DPD 가 hydration 후에 S-DHMF(S-Dihydroxymethylfuran) 으로변화다시한번더 hydration 후 S-THMF(S-Tetrahydroxymethylfuran) 으로전환후 Boric acid 와반응하여 Vibrio harveyi 가사용한 AI-2 로변환완료 Route2: DPD 가 hydration 후에 R-DHMF(S-Dihydroxymethylfuran) 으로변화다시한번더 hydration 후 R-THMF(S-Tetrahydroxymethylfuran) 으로전환후 Salmonella typhimurium 가사용한 AI-2 로변환완료

42(4)-13(p ).fm

42(4)-13(p ).fm The Korean Journal of Microbiology, Vol. 42, No. 4, December 2006, p. 277-285 Copyright 2006, The Microbiological Society of Korea w ell ü l Quorum Sensing autoinducer w x xá v 1 Á 2 Á 3 Á *» w œw» w p