このアプリについて
バクテリオファージ（ファージ）は、細菌にとりつくウイルス。ここでは、研究でいちばん調べられてきた T4 ファージと大腸菌を使う。T4 は頭が 120×86nm、しっぽと合わせて約 200nm。大腸菌（約 2µm）の10分の1ほどの大きさ。
見かた: 下のスライダーで時間を動かす（▶で再生）。ホイール・ピンチで拡大、ドラッグで移動。マウスを乗せる（スマホはタップ）と、そこにあるものの説明が出る。細菌全体（約2µm）から、たんぱく質が見える大きさ（横はば約20nm）まで寄れて、寄るほど細かく描く。「見どころ」を押すと、その時間・その場所へ寄る。
文の右の印: 研究の値 研究で測られたこと・確かなこと 目安 時刻や数の目安・推定 模式 見せ方のための形
くっつく・刺さる・DNA が入る
- 6本の長い脚（長い尾繊維、約145nm）の先が、細菌の表面の決まった印（受け手）にくっつく。大腸菌 K-12 では外膜のたんぱく質 OmpC。研究の値
- 3本以上の脚がくっつくと、基盤が六角形（直径約52nm）から星形（約61nm）に変わり、短い脚が約100°まわって LPS の内側の糖にしっかりくっつく。研究の値
- しっぽのさや（gp18 が6個×23段）が基盤の側から1段ずつ縮み（92.5→42nm、1段のねじれは17.2°）、中の管が約345°回りながら押し出されて外膜を突きぬける。針のリゾチームが細胞壁に穴をあけ、DNA が入る。研究の値
- 受け手をなくした変異の大腸菌（OmpC がなく、LPS の糖の鎖も短い）には付けない（もしも）。研究の値
細菌の中（37℃・栄養のある液での目安）
- 1分で細菌自身のたんぱく質がほとんど作られなくなる。研究の値 T4 の EndoII（CCGC を切る）・EndoIV（シトシンの DNA を切る）が細菌の DNA をこわし、T4 の DNA の材料にする（このアプリでは2〜10分）。目安
- T4 は細菌の RNA ポリメラーゼを最後まで使い、Alt・AsiA・MotA・gp55・gp33・gp45 を付けかえて、早期 → 中期 → 後期の遺伝子を読ませる。研究の値
- 約5分で T4 の DNA のコピー（gp41・gp43・gp45・gp44/62・gp61・gp32 など。毎秒約400〜500塩基）、約9分から頭・しっぽ・脚の部品。目安
- 頭: 入口 gp20 のまわりに足場（gp22・gp21）と殻（gp23 約930〜960個・頂点 gp24）→ モーター gp17 が DNA をつめる（平均 毎秒約700塩基対、最大約2000、1つ約4〜5分）→ ゲノムの1.02倍で切る。研究の値
- しっぽは頭と別に組み立てられ（基盤 → 管 → さや → ふた）、DNA のつまった頭に付く。長い脚が最後。研究の値
- 最初の完成品は約12〜15分、約22〜25分で破裂し、100〜150個が出てくる。目安
- ホリン（t）が決まった時刻に内膜に穴をあけ、リゾチーム（e）が細胞壁を切って破れる。研究の値
- もしも: 約4分すぎに来た別のファージの DNA は中に入れない（重感染排除）。5分すぎに別のファージが来ると、破裂が大きくおくれる（溶菌阻止）。DNA にブドウ糖の目印がない変異の T4 は、大腸菌の制限酵素に切られる。研究の値
人のからだから・次々にうつる
- はじめは人のからだ（身長約1.7m）から、おなかの大腸 → 大腸のかべ（粘膜・陰窩・粘膜下層・筋肉）→ 粘液 → 大腸菌（約2µm）へ寄っていく。人の体の細菌は約40兆個で、ほとんどが大腸にいる（Sender ら 2016）。目安
- 大腸の粘液は2層で、内側の層には細菌がほとんど入れず、外側の層に細菌がすむ（Johansson ら 2008）。大腸の中身1gにウイルスは約1億〜100億個、ほとんどがファージ（Shkoporov と Hill 2019）。研究の値
- 組み立て: 頭は内膜の上で、入口 gp20 → 足場 gp22・gp21 → 殻 gp23（入口の側から付いていく）。はさみ gp21 が足場を切ると空の殻が離れ、DNA をつめはじめると殻がふくらみ、Hoc・Soc が付く。つめおわると首（gp13・gp14）が付き、別に組み立てたしっぽ（基盤 → 管 → さや → ふた）がはまり、最後に長い脚が付く。部品は運ばれるのではなく、熱でふらふら動いてぶつかったときにくっつく（自己集合）。研究の値
- 破れて出る: ホリンが内膜に穴をあけ、リゾチームが細胞壁を切ると、細菌は棒の形を保てなくなり、スパニンが外膜を破って中身がいっせいに出る（Kongari ら 2018 などのスパニンの研究）。細菌は死に、膜はちぎれたかけらになる。研究の値
- 次々にうつる: 出てきたファージが近くの細菌にとりつき、同じことがくり返される。どの細菌にいつうつるか、広がる速さ、まわりの細菌の位置・泳ぎ方は模式。「ファージ 約○個」は（破れた細菌の数）×（物語の細菌から出た数）の目安。模式
簡単にしているところ
- 立体を横から見た平面の図にしている。6本の脚は奥行きを色の濃さで表す。
- スライダーの区間ごとに時間の進み方がちがう（近づく・くっつくはミリ秒、細菌の中は分）。区間の名前と本当の時間を出している。模式
- 近づくときのゆれ（ブラウン運動）・脚がくっつく時刻は演出。ファージを半径約75nm の球とみなすと、拡散係数は約3µm²/秒（ストークス・アインシュタインの式）。目安
- さやが縮む速さ、DNA が入るのにかかる時間は、T4 でははっきり測られていない。管がどこまで入るかも模式。模式
- 細菌の中の分子（リボソーム・RNA ポリメラーゼ・コピーの機械・酵素）の数・置き場所・色は模式。大きさはおおよそ本当に合わせた（リボソーム約20nm、RNA ポリメラーゼ約15nm、DNA の太さ約2nm）。たんぱく質は丸や四角で描き、本当の原子の形ではない。模式
- 流れる点は、1つがたくさんの分子の代わり。どこからどこへ流れるかは本当の順番どおりだが、点の数と動きは模式。「頭の殻 gp23 約○個」は、1つの頭に約960個（Rao と Black 2010）×作りはじめた頭の数で計算している。T4 の DNA の本数は、頭につめる数に足りるように決めた目安。模式
- 頭が作られる速さは「最初の完成が約12〜15分・破裂までに100〜150個」に合うように決めた。溶菌阻止で破裂がどれだけおくれるかは条件で大きく変わる（数十分〜数時間）。アプリでは約60分にした。模式
- DNA の長さは大きく短くしている（T4 の DNA は約57µm、細菌の DNA は約1.6mm で、どちらも細菌の長さ約2µm よりずっと長く、ぎゅっと折りたたまれている）。リボソームの数も本当（数万個）よりずっと少ない。大きさ（太さ・直径）は本当に合わせている。模式
- べん毛（太さ約20nm、長さ5〜10µm。Turner ら 2000）・線毛（太さ約7nm、体じゅうにほぼ均等に生える）の本数と向きは模式。寄ったときは薄く描く。模式
- 頭の中の DNA は、殻の内側のかべに沿って何層にも並ぶ（層の間かく約2.5nm）。つめるときは入口から入った1本の DNA が外側の層から巻いていく、と描いている（よく使われる考え方。くわしい順番はまだ研究中）。模式
- DNA を入れおわったファージ（ぬけがら）はもう感染できず、細菌の表面にささったまま残る。細菌が破れると、ささっていた膜のかけらといっしょに流される。研究の値
- 細菌の中は立体を平面に重ねて描いているので、頭どうしが重なって見える。破れるときの形のくずれ方・かけらの数は模式。模式
- 「見た目: 本物に近い」: 本物のファージや細菌は光の波長より小さく、色はない。電子顕微鏡の写真のように色を抜き、名前の札を消し、細胞の中をぎっしりにした見え方。形と大きさは「わかりやすい」と同じ。模式
- 学習用に簡単にしています。医療や実験の判断には使えません。
おもな出どころ
- Miller ES, Kutter E, Mosig G ほか (2003) Bacteriophage T4 genome. Microbiology and Molecular Biology Reviews 67:86–156（ゲノム 168,903 塩基対、感染1分後の細菌のたんぱく質、さや 98.4→36nm、3本以上の長い脚、短い脚と LPS、ヘッドフル、重感染排除、溶菌阻止、ホリン、100〜150個、McrA／McrBC）
- Yap ML, Rossmann MG (2014) Structure and function of bacteriophage T4. Future Microbiology 9:1319–1327（しっぽ・長い脚 145nm）
- Fokine A ほか (2004) Molecular architecture of the prolate head of bacteriophage T4. PNAS 101:6003–6008／Rao VB ほか (2023) Viruses の総説（頭 120×86nm）
- Taylor NMI ほか (2016) Structure of the T4 baseplate and its function in triggering sheath contraction. Nature 533:346–352
- Hu B, Margolin W, Molineux IJ, Liu J (2015) Structural remodeling of bacteriophage T4 and host membranes during infection initiation. PNAS 112:E4919–E4928（K-12 の OmpC・B の LPS、基盤の形の変化）
- Yu F, Mizushima S (1982) Roles of lipopolysaccharide and outer membrane protein OmpC of Escherichia coli K-12 in the receptor function for bacteriophage T4. Journal of Bacteriology 151:718–722／Washizaki A ほか (2016) MicrobiologyOpen 5:1003–1015（OmpC がないときの LPS の糖）
- Fuller DN ほか (2007) Single phage T4 DNA packaging motors exhibit large force generation, high velocity, and dynamic variability. PNAS 104:16868–16873
- Leiman PG, Arisaka F, van Raaij MJ ほか (2010) Morphogenesis of the T4 tail and tail fibers. Virology Journal 7:355（くさびの順番、さや・管・基盤の数と大きさ、さやの縮み方、針、長い脚と短い脚、ふた）
- Rao VB, Black LW (2010) Structure and assembly of bacteriophage T4 head. Virology Journal 7:356（殻のたんぱくの数、入口、つめこみモーター、ヘッドフル、Hoc・Soc、内部たんぱく）
- Sinha NK, Morris CF, Alberts BM (1980) Efficient in vitro replication of double-stranded DNA templates by a purified T4 bacteriophage replication system. Journal of Biological Chemistry 255:4290–4293（体の中の分かれ目は毎秒約500塩基）
- Dong F, Weitzel SE, von Hippel PH (1996) A coupled complex of T4 DNA replication helicase (gp41) and polymerase (gp43) can perform rapid and processive DNA strand-displacement synthesis. PNAS 93:14456–14461
- Revel HR (1967) Restriction of nonglucosylated T-even bacteriophage. Virology 31:688–701
- Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLOS Biology 14:e1002533（体の細菌 約40兆個、大腸の中身1gに約1000億個）
- Shkoporov AN, Hill C (2019) Bacteriophages of the human gut: the "known unknown" of the microbiome. Cell Host & Microbe 25:195–209（腸のウイルスの数、ほとんどがファージ）
- Johansson MEV, Phillipson M, Petersson J ほか (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. PNAS 105:15064–15069
- Kongari R, Rajaure M, Cahill J ほか (2018) Phage spanins: diversity, topological dynamics and gene convergence. BMC Bioinformatics 19:326（外膜を破るスパニン）
- Turner L, Ryu WS, Berg HC (2000) Real-time imaging of fluorescent flagellar filaments. Journal of Bacteriology 182:2793–2801（大腸菌のべん毛）
- Matias VRF, Al-Amoudi A, Dubochet J, Beveridge TJ (2003) Cryo-transmission electron microscopy of frozen-hydrated sections of Escherichia coli and Pseudomonas aeruginosa. Journal of Bacteriology 185:6112–6118（外膜・細胞壁の厚さ）
使っているもの
フォント: Google Fonts（Dela Gothic One・Zen Kaku Gothic New・IBM Plex Mono。SIL Open Font License）。ライブラリは使っていない（Canvas 2D）。
About this app
A bacteriophage (phage) is a virus that infects bacteria. This app uses the T4 phage, the most studied one, and E. coli. T4's head is 120×86 nm, and with the tail it is about 200 nm long: about one tenth the size of E. coli (about 2 µm).
How to use: move through time with the slider at the bottom (▶ to play). Wheel or pinch to zoom, drag to move. Hover (tap on phones) to see what is there. You can zoom from the human body down to the size where proteins are visible (about 20 nm across), and the closer you get, the more detail is drawn. Click a highlight to jump to that time and place.
Marks after sentences: measured measured in research or well established rough guide estimated times and numbers schematic shapes chosen for display
Sticking, piercing, DNA going in
- The tips of the 6 long legs (long tail fibers, about 145 nm) stick to a specific mark on the bacterial surface (a receptor). In E. coli K-12 this is the outer-membrane protein OmpC. measured
- When 3 or more legs stick, the baseplate changes from a hexagon (about 52 nm across) to a star (about 61 nm), and the short legs swing about 100° to grip the inner sugars of the LPS. measured
- The tail sheath (gp18, 6 copies × 23 rings) contracts ring by ring from the baseplate (92.5 → 42 nm, 17.2° twist per ring), and the tube inside is pushed out while turning about 345°, piercing the outer membrane. Lysozyme on the needle opens a hole in the cell wall and the DNA goes in. measured
- It cannot attach to mutant E. coli that lost its receptors (no OmpC and short LPS sugar chains) (what-if). measured
Inside the bacterium (rough guide at 37 °C in rich broth)
- Within 1 minute the bacterium makes almost none of its own proteins. measured T4's EndoII (cuts CCGC) and EndoIV (cuts cytosine DNA) break down the bacterial DNA and reuse it to build T4 DNA (2-10 minutes in this app). rough guide
- T4 uses the bacterial RNA polymerase to the end, swapping in Alt, AsiA, MotA, gp55, gp33 and gp45 so that early → middle → late genes get read. measured
- T4 DNA copying at about 5 minutes (gp41, gp43, gp45, gp44/62, gp61, gp32 and others; about 400-500 bases per second), and parts for heads, tails and legs from about 9 minutes. rough guide
- Head: scaffold (gp22, gp21) and shell (about 930-960 gp23, corners gp24) around the portal gp20 → the gp17 motor packs DNA (about 700 base pairs per second on average, up to about 2,000; about 4-5 minutes per head) → cut at 1.02 genomes. measured
- The tail is built separately from the head (baseplate → tube → sheath → caps) and attaches to a DNA-filled head. The long legs come last. measured
- The first finished phages at about 12-15 minutes; it bursts at about 22-25 minutes and 100-150 come out. rough guide
- At a set time the holin (t) opens holes in the inner membrane, lysozyme (e) cuts the cell wall, and the cell bursts. measured
- What if: DNA from another phage arriving after about 4 minutes cannot get in (superinfection exclusion). If another phage arrives after 5 minutes, bursting is greatly delayed (lysis inhibition). Mutant T4 without glucose tags on its DNA is cut by E. coli restriction enzymes. measured
From the human body, and spreading on
- It starts with the human body (about 1.7 m tall) and zooms into the colon → the colon wall (mucosa, crypts, submucosa, muscle) → mucus → E. coli (about 2 µm). The human body holds about 40 trillion bacteria, mostly in the colon (Sender et al. 2016). rough guide
- Colon mucus has two layers: bacteria can hardly enter the inner one and live in the outer one (Johansson et al. 2008). One gram of colon contents holds about 100 million to 10 billion viruses, mostly phages (Shkoporov and Hill 2019). measured
- Assembly: the head forms on the inner membrane as portal gp20 → scaffold gp22, gp21 → shell gp23 (added starting from the portal side). When the gp21 scissors cut the scaffold, the empty shell leaves; when DNA packing starts, the shell expands and Hoc and Soc attach. After packing, the neck (gp13, gp14) attaches, a separately built tail (baseplate → tube → sheath → caps) snaps on, and the long legs attach last. Parts are not carried: they jiggle around from heat and stick when they bump into each other (self-assembly). measured
- Bursting: when holins open holes in the inner membrane and lysozyme cuts the cell wall, the bacterium cannot keep its rod shape; spanins break the outer membrane and the contents rush out (studies of spanins such as Kongari et al. 2018). The bacterium dies and its membranes become torn pieces. measured
- Spreading on: the released phages infect nearby bacteria and the same thing happens again. Which bacterium is infected when, how fast they spread, and the positions and swimming of the other bacteria are schematic. "About N phages" is a rough guide: (number of burst bacteria) × (number released by the story's bacterium). schematic
What is simplified
- The 3D scene is drawn as a flat side view. Depth of the 6 legs is shown by shade.
- Time runs at different rates in each part of the slider (milliseconds while approaching and sticking, minutes inside). The part name and the real time are shown. schematic
- The wobble while approaching (Brownian motion) and the timing of leg sticking are staged. Treating the phage as a sphere of about 75 nm radius, its diffusion coefficient is about 3 µm²/s (Stokes-Einstein equation). rough guide
- How fast the sheath contracts and how long DNA entry takes have not been measured precisely for T4. How far the tube goes in is also schematic. schematic
- The number, positions and colors of molecules inside the bacterium (ribosomes, RNA polymerase, copying machines, enzymes) are schematic. Sizes roughly match reality (ribosome about 20 nm, RNA polymerase about 15 nm, DNA about 2 nm thick). Proteins are drawn as circles and boxes, not their real atomic shapes. schematic
- Each moving dot stands for many molecules. Where they flow from and to follows the real order, but the number and motion of dots are schematic. "Head shell gp23, about N" is calculated as about 960 per head (Rao and Black 2010) × the number of heads started. The number of T4 DNA copies is a rough guide chosen to be enough for the heads being packed. schematic
- The rate of head production was set to match "first finished at about 12-15 minutes, 100-150 by bursting". How long lysis inhibition delays bursting varies a lot (tens of minutes to hours); this app uses about 60 minutes. schematic
- DNA length is greatly shortened (T4 DNA is about 57 µm and bacterial DNA about 1.6 mm, both far longer than the 2 µm bacterium and tightly folded). There are also far fewer ribosomes than in reality (tens of thousands). Thickness and diameter match reality. schematic
- The number and direction of flagella (about 20 nm thick, 5-10 µm long; Turner et al. 2000) and pili (about 7 nm thick, spread almost evenly over the body) are schematic. They are drawn faint when zoomed in. schematic
- DNA in the head lies in many layers along the inner wall of the shell (about 2.5 nm apart). Packing is drawn as one DNA strand entering through the portal and winding from the outer layer inward (a commonly used idea; the exact order is still being studied). schematic
- A phage that has injected its DNA (a ghost) cannot infect again and stays stuck on the bacterial surface. When the bacterium bursts, it drifts away with the piece of membrane it is stuck to. measured
- The inside of the bacterium is 3D flattened onto a plane, so heads appear to overlap. How the shape falls apart when bursting and the number of pieces are schematic. schematic
- "Look: realistic": real phages and bacteria are smaller than the wavelength of light and have no color. This look removes color like an electron micrograph, hides the labels, and packs the inside of the cell. Shapes and sizes are the same as "easy to read". schematic
- This is simplified for learning. Do not use it for medical or lab decisions.
Main sources
- Miller ES, Kutter E, Mosig G, et al. (2003) Bacteriophage T4 genome. Microbiology and Molecular Biology Reviews 67:86–156 (genome of 168,903 bp, host proteins 1 minute after infection, sheath 98.4→36 nm, 3 or more long legs, short legs and LPS, headful packaging, superinfection exclusion, lysis inhibition, holin, 100-150 progeny, McrA/McrBC)
- Yap ML, Rossmann MG (2014) Structure and function of bacteriophage T4. Future Microbiology 9:1319–1327 (tail, long legs 145 nm)
- Fokine A, et al. (2004) Molecular architecture of the prolate head of bacteriophage T4. PNAS 101:6003–6008 / Rao VB, et al. (2023) review in Viruses (head 120×86 nm)
- Taylor NMI, et al. (2016) Structure of the T4 baseplate and its function in triggering sheath contraction. Nature 533:346–352
- Hu B, Margolin W, Molineux IJ, Liu J (2015) Structural remodeling of bacteriophage T4 and host membranes during infection initiation. PNAS 112:E4919–E4928 (OmpC of K-12, LPS of B, baseplate shape change)
- Yu F, Mizushima S (1982) Roles of lipopolysaccharide and outer membrane protein OmpC of Escherichia coli K-12 in the receptor function for bacteriophage T4. Journal of Bacteriology 151:718–722 / Washizaki A, et al. (2016) MicrobiologyOpen 5:1003–1015 (LPS sugars without OmpC)
- Fuller DN, et al. (2007) Single phage T4 DNA packaging motors exhibit large force generation, high velocity, and dynamic variability. PNAS 104:16868–16873
- Leiman PG, Arisaka F, van Raaij MJ, et al. (2010) Morphogenesis of the T4 tail and tail fibers. Virology Journal 7:355 (wedge order, numbers and sizes of sheath, tube and baseplate, sheath contraction, needle, long and short legs, caps)
- Rao VB, Black LW (2010) Structure and assembly of bacteriophage T4 head. Virology Journal 7:356 (shell protein numbers, portal, packaging motor, headful packaging, Hoc and Soc, internal proteins)
- Sinha NK, Morris CF, Alberts BM (1980) Efficient in vitro replication of double-stranded DNA templates by a purified T4 bacteriophage replication system. Journal of Biological Chemistry 255:4290–4293 (forks move about 500 bases per second in the cell)
- Dong F, Weitzel SE, von Hippel PH (1996) A coupled complex of T4 DNA replication helicase (gp41) and polymerase (gp43) can perform rapid and processive DNA strand-displacement synthesis. PNAS 93:14456–14461
- Revel HR (1967) Restriction of nonglucosylated T-even bacteriophage. Virology 31:688–701
- Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLOS Biology 14:e1002533 (about 40 trillion bacteria in the body, about 100 billion per gram of colon contents)
- Shkoporov AN, Hill C (2019) Bacteriophages of the human gut: the "known unknown" of the microbiome. Cell Host & Microbe 25:195–209 (number of gut viruses, mostly phages)
- Johansson MEV, Phillipson M, Petersson J, et al. (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. PNAS 105:15064–15069
- Kongari R, Rajaure M, Cahill J, et al. (2018) Phage spanins: diversity, topological dynamics and gene convergence. BMC Bioinformatics 19:326 (spanins that break the outer membrane)
- Turner L, Ryu WS, Berg HC (2000) Real-time imaging of fluorescent flagellar filaments. Journal of Bacteriology 182:2793–2801 (E. coli flagella)
- Matias VRF, Al-Amoudi A, Dubochet J, Beveridge TJ (2003) Cryo-transmission electron microscopy of frozen-hydrated sections of Escherichia coli and Pseudomonas aeruginosa. Journal of Bacteriology 185:6112–6118 (thickness of the outer membrane and cell wall)
What it uses
Fonts: Google Fonts (Dela Gothic One, Zen Kaku Gothic New, IBM Plex Mono; SIL Open Font License). No libraries (Canvas 2D).